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G T Wolf

Publications and source records attributed to G T Wolf.

At least 37 records · Page 2Linked to original sources
PubMed1999

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PURPOSE: To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). PATIENTS AND METHODS: Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. RESULTS: Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. CONCLUSIONS: Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Dose-Response Relationship, Radiation↗
PubMed1998

Long-term quality of life after treatment of laryngeal cancer. The Veterans Affairs Laryngeal Cancer Study Group.

OBJECTIVE: To assess long-term quality of life in surviving patients with advanced laryngeal cancer. DESIGN: A follow-up long-term quality-of-life survey of patients randomized to the Veterans Affairs Laryngeal Cancer Study No. 268 on induction chemotherapy and radiation (CT + RT) vs surgery and RT. SETTING AND PATIENTS: Forty-six (71%) of the 65 surviving patients with prior stage III or IV laryngeal cancer who could be contacted completed the survey: 25 from the surgery and RT group and 21 from the CT + RT group. Baseline demographic and clinical characteristics among survey respondents were similar, except that those in the CT + RT group were significantly older (mean, 61.2 years) than those in the surgery and RT group (mean, 55.7 years; P<.05). INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients completed the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Studies Short-Form 36 (SF-36) general health survey, the Beck Depression Inventory as well as smoking and alcohol consumption surveys. RESULTS: Patients randomized to the CT + RT group had significantly better (P<.05) quality-of-life scores on the SF-36 mental health domain (76.0) than the surgery and RT group (63.0), and also had better HNQOL pain scores (81.3 vs 64.3). Compared with patients who underwent laryngectomy, patients with intact larynges (CT + RT with larynx) had significantly less bodily pain (88.5 vs 56.5), better scores on the SF-36 mental health (79.8 vs 64.7), and better HNQOL emotion (89.7 vs 79.4) scores. More patients in the surgery and RT group (28%) were depressed than in the CT + RT group (15%). CONCLUSION: Better quality-of-life scores in the CT + RT groups appear to be related to more freedom from pain, better emotional well-being, and lower levels of depression than to preservation of speech function.

Alcohol Drinking↗
PubMed1998

Functional outcomes following treatment for advanced laryngeal cancer. Part I--Voice preservation in advanced laryngeal cancer. Part II--Laryngectomy rehabilitation: the state of the art in the VA System. Research Speech-Language Pathologists. Department of Veterans Affairs Laryngeal Cancer Study Group.

This two-part investigation assessed functional outcomes related to communication (including amount of speech therapy), swallowing and eating, and employment status for patients who received one of the two treatment modalities for advanced laryngeal cancer (stage III or IV laryngeal squamous cell carcinoma) in Veterans Administration Cooperative Study #268. One hundred sixty-six patients were randomized to primary surgery (laryngectomy) and radiotherapy (RT), and 166 to induction chemotherapy (CT) and RT. The first investigation dealt with examining and comparing functional outcomes for patients in the two treatment arms of the main study. Results showed clearly that patients with advanced laryngeal cancer are better off from the standpoint of speech communication if they can be treated for this disease without removal of the larynx. In contrast, there were few significant differences between patient groups for other non-speech-related measures. The second investigation focused on communication-related outcomes associated with the rehabilitation of total laryngectomy patients. Results revealed that only relatively small percentages of total laryngectomy patients (6%) developed usable esophageal speech or remained nonvocal (8%), and that a majority of patients ended up as users of artificial electrolarynx (55%) or tracheoesophageal (31%) speech. The results from both investigations are discussed with respect to factors that can influence the rehabilitation process and long-term outcome status of patients who are treated for advanced laryngeal cancer with these two strategies.

Adult↗
PubMed1997

p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group.

OBJECTIVE: To determine the relationship of p53 mutations in advanced laryngeal carcinomas to p53 immunohistochemistry, organ preservation, and patient survival. DESIGN: Paraffin-embedded tumor specimens were obtained from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multi-institutional randomized clinical trial comparing induction chemotherapy (cisplatin and fluorouracil) plus radiation therapy surgery plus postoperative radiation therapy. Tumor specimens were analyzed for p53 mutations in exons 5 through 8 by using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing of all variants. Five-year follow-up data were available for all patients studied. SUBJECTS: Forty-four patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study from whom paraffin-embedded tumor specimens were readily available. RESULTS: p53 immunostaining did not correlate with p53 SSCP and DNA sequencing results. More than half (62% [16/26]) of the tumors that overexpressed p53 immunohistochemically did not have a detectable p53 gene mutation. Similarly, 39% (7/18) of tumors that did not overexpress p53 did have a p53 gene mutation. p53 mutations were present in 39% of tumors tested. Mutations within exon 5 made up 41% of p53 gene mutations in laryngeal carcinomas. Transitions were the most common type of mutation in this study (92% of mutations). CONCLUSIONS: The presence of a p53 mutation as detected by SSCP is associated with decreased patient survival. Further study is required to confirm this relationship and to determine whether specific p53 mutations predict organ preservation.

Carcinoma, Squamous Cell↗
PubMed1997

Frequent loss of heterozygosity on chromosome arm 18q in squamous cell carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23.

OBJECTIVES: To determine the frequency and regions of loss on chromosome arm 18q in uncultured head and neck squamous cell carcinomas. DESIGN: Polymerase chain reaction amplification of DNA extracted from 18 tumor specimens (1 patient had 2 tumors) and blood samples from 17 patients with head and neck squamous cell carcinoma was performed using primers flanking 16 microsatellite repeat polymorphisms spanning most of chromosome 18q. DNA was extracted only from specimens with greater than 70% tumor nuclei. SETTING: Research university. PATIENTS: Seventeen individuals with newly diagnosed head and neck cancer. MAIN OUTCOME MEASURE: Loss of heterozygosity (LOH). RESULTS: There was LOH at more than 1 locus in 52% (9/ 17) of the tumors; 3 tumors had LOH at all informative markers. Four had loss at only 1 locus, raising the total with loss to 12 (75%) of 16. Loss of 18q11.1-q12.3 in 4 tumors without distal loss defines a proximal region of loss. Loss of heterozygosity affecting 18q21.1 in 1 tumor, without proximal loss and LOH for 18q21.1, 18q22, or 18q23 in 9 (52%) of 17 tumors defines a distal region of loss. CONCLUSIONS: Loss of heterozygosity on chromosome arm 18q is not an artifact of in vitro culture. The finding of 18q LOH in 50% to 70% tumors makes 18q an important region for study. Regions 18q11.1-q12.3 and 18q21.1-q23 are common regions of loss, indicating that there may be more than one 18q tumor suppressor gene involved in the genesis and progression of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1997

Clinical outcome of continuous facial nerve monitoring during primary parotidectomy.

OBJECTIVES: To assess whether continuous facial nerve monitoring during parotidectomy is associated with a lower incidence of facial nerve paresis or paralysis compared with parotidectomy without monitoring and to assess the cost of such monitoring. DESIGN: A retrospective analysis of outcomes for patients who underwent parotidectomy with or without continuous facial nerve monitoring. SETTING: University medical center. PATIENTS: Fifty-six patients undergoing parotidectomy in whom continuous electromyographic monitoring was used and 61 patients in whom it was not used. MAIN OUTCOME MEASURES: (1) The incidence of early and persistent facial nerve paresis or paralysis and (2) the cost associated with facial nerve monitoring. RESULTS: Early, unintentional facial weakness was significantly lower in the group monitored by electromyograpy (43.6%) than in the unmonitored group (62.3%) (P=.04). In the subgroup of patients without comorbid conditions or surgeries, early weakness in the monitored group (33.3%) remained statistically lower than the rate of early weakness in the unmonitored group (57.5%) (P=.03). There was no statistical difference in the final facial nerve function or incidence of permanent nerve injury between the groups or subgroups. After multivariate analysis, nonmonitored status (odds ratio [OR], 3.22), advancing age (OR, 1.47 per 10 years), and longer operative times (OR, 1.3 per hour) were the only significant independent predictive variables significantly associated with early postoperative facial weakness. The incremental cost of facial nerve monitoring was $379. CONCLUSIONS: The results suggest that continuous electromyographic monitoring of facial muscle during primary parotidectomy reduces the incidence of short-term postoperative facial paresis. Advantages and disadvantages of this technique need to be considered together with the additional costs in deciding whether routine use of continuous monitoring is a useful, cost-effective adjunct to parotid surgery.

Cost-Benefit Analysis↗
PubMed1997

Head and neck cancer-specific quality of life: instrument validation.

BACKGROUND: The disfigurement and dysfunction associated with head and neck cancer affect emotional well-being and some of the most basic functions of life. Most cancer-specific quality-of-life assessments give a single composite score for head and neck cancer-related quality of life. OBJECTIVE: To develop and evaluate an improved multidimensional instrument to assess head and neck cancer-related functional status and well-being. METHODS: The item selection process included literature review, interviews with health care workers, and patient surveys. A survey with 37 disease-specific questions and the SF-12 survey were administered to 253 patients in 3 large medical centers. Factor analysis was performed to identify disease-specific domains. Domain scores were calculated as the standardized score of the component items. These domains were assessed for construct validity based on clinical hypotheses and test-retest reliability. RESULTS: Four relevant domains were identified: Eating (6 items), Communication (4 items), Pain (4 items), and Emotion (6 items). Each had an internal consistency (Cronbach alpha value) of greater than 0.80. Construct validity was demonstrated by moderate correlations with the SF-12 Physical and Mental component scores (r=0.43-0.60). Test-retest reliability for each domain demonstrated strong reliability between the 2 time points. Correlations were strong for each individual question, ranging from 0.53 to 0.93. Construct validity testing demonstrated that the direction of differences for each domain were as hypothesized. CONCLUSION: The Head and Neck Quality of Life questionnaire is a promising multidimensional tool with which to assess head and neck cancer-specific quality of life.

Factor Analysis, Statistical↗
PubMed1997

Planned early neck dissection before radiation for persistent neck nodes after induction chemotherapy.

Optimal management of advanced neck metastases as part of an organ preservation treatment approach for head and neck squamous carcinoma (HNSC) is unclear. Since 1989, our management paradigm for patients on organ preservation was modified to incorporate planned early neck dissection before radiation therapy for patients who did not achieve a complete response (CR) of neck nodes after induction chemotherapy (IC). The purpose of this study was to determine if planned early neck dissection is a safe and effective approach in the management of advanced nodal disease as part of organ preservation. Fifty-eight consecutive patients with advanced HNSC who were entered in organ preservation trials using induction chemotherapy and radiation with surgical salvage were studied. Median follow-up was 26 months. Of the 58 patients, 71% were stage IV. Patients were grouped by nodal response to chemotherapy and N class, and were analyzed with respect to patterns of recurrence, complications, and survival. Overall, the rate of CR of neck nodes was 49%. Fifty-one percent had less than a complete response of neck nodes after IC and required planned early neck dissection. There were no significant differences in patterns of recurrence, complications, interval time to start of radiation, recurrence, or survival rates between the CR and less than CR groups. These data suggest that planned early neck dissection for patients with less than CR in the neck after IC is not detrimental with respect to neck relapse or overall survival. We believe that planned early neck dissection can be safely incorporated into future organ preservation treatment protocols for patients with advanced head and neck carcinoma.

Adult↗
PubMed1996

Parotid gland sparing in patients undergoing bilateral head and neck irradiation: techniques and early results.

PURPOSE: To minimize xerostomia in patients receiving bilateral head and neck irradiation (RT) by using conformal RT planning to spare a significant volume of one parotid gland from radiation. METHODS AND MATERIALS: The study involved 15 patients with head and neck tumors in whom bilateral neck radiation was indicated. The major salivary glands and the targets (tumor, surgical bed, metastases to lymph nodes, and the locations of lymph nodes at risk for metastases) were outlined on axial computed tomography images. Beam's-eye view (BEV) displays were used to construct conformal beams that delivered the prescribed doses to the targets while sparing from direct radiation most of one parotid gland. The gland that was planned to be spared resided in the neck side that was judged in each patient to be at a lesser risk of metastatic disease. Major salivary gland flow rates and the responses to a subjective xerostomia questionnaire were assessed before, during, and after radiation. RESULTS: Radiation planning for patients with central oropharyngeal tumors required the generation of multiple axial nonopposed beams. The resulting isodoses encompassed the targets, including the retropharyngeal nodes and the jugular nodes up to the base of skull bilaterally, while limiting the dose to the oral cavity, spinal cord, and one parotid gland. For patients with lateralized tumors, the ipsilateral neck side was treated up to the base of the skull; in the contralateral neck side, the treatment included the subdigastric nodes but excluded the jugular nodes at the base of the skull and most of the parotid gland. This was accomplished by a moderate gantry angle that was chosen using the BEV displays. Three months following the completion of radiation, the spared parotid glands retained on average 50% of their unstimulated and stimulated flows. In contrast, no saliva flow was measured from the unspared glands in any of the patients. Subjective xerostomia was absent, mild, or not different from that reported before radiation in 10 of 15 patients (67%). CONCLUSION: Partial parotid gland sparing is feasible by using three-dimensional planning in patients undergoing bilateral head and neck radiation. Approximately 50% of the saliva flow from the spared glands may be retained, and most patients thus treated have no or mild xerostomia in the early period after the completion of radiation. Whether tumor control and late complications are comparable to standard radiation will be assessed as more experience is gained.

Aged↗
PubMed1996

Regional metastases in patients with advanced laryngeal cancer. Department of Veterans Affairs Laryngeal Cancer Study Group.

OBJECTIVES: To determine patterns of regional metastases in patients with advanced squamous cell carcinoma of the larynx and the effect of these patterns on regional and distant tumor recurrence and disease-free and overall survival. METHODS: One hundred fifty-nine patients treated with conventional surgery and radiation in the Veterans Affairs Cooperative Study were studied. Ninety-three of the patients underwent modified or classic radical neck dissection. Median follow-up was 5 years. Patient data collected included age, gender, alcohol consumption, tobacco use, and performance status. Tumor variables evaluated included TNM classification, tumor site, surface area, presence of ulceration and invasion, and histologic growth pattern. Histologically positive regional lymph nodes were examined for level, number, site, and extracapsular spread. Outcome variables included time and location of recurrence, distant metastases, and survival. RESULTS: Regional metastases were more common in supraglottic than glottic or subglottic tumors (P < .001) and in tumors with larger surface dimensions (P = .004). Cervical metastases were associated with decreased disease-free interval (P < .001) and survival (P = .001) and increased distant metastases (P < .001). Presence of 3 or more positive nodes predicted distant recurrence (P < .001) and decreased survival (P < .001, multivariate analysis). An analysis of lymph node involvement (levels I-V) indicated that level 1 and 5 involvement was a significant prognostic factor. Age, sex, race, and tobacco or alcohol use were not associated with number or extent of regional metastases. CONCLUSIONS: These findings confirm the prognostic importance of number and level of lymph nodes in advanced laryngeal cancer. The association of distant metastases with number and level of regional nodes indicates a use for these variables in considering adjuvant chemotherapy.

Carcinoma, Squamous Cell↗
PubMed1996

Unknown primary of the head and neck.

The occurrence of metastases to the cervical lymph nodes from an unknown primary tumour is seen in approximately three to six per cent of patients with cervical adenopathy and the primary tumour commonly remains elusive. Single modality treatment is occasionally advocated but combined treatment seems to obtain the best results. A retrospective analysis of patients' charts with unknown primary of the head and neck in the University of Michigan Medical Center was undertaken for the years 1978-1992. Forty-eight records met study criteria and were reviewed. Our series' size and heterogeneity prevents drawing conclusions regarding treatment effectiveness. The majority (67.5 per cent) of our patients were treated by surgery followed by irradiation. Our overall survival rates compare favourably with the general statistics although it should be noted that longer follow-up in our first group of patients may alter our results. Extracapsular spread did not adversely affect survival in our small series of five cases. We discovered six primary sites within one year and three additional cases within four years. The primary site was included in the radiation fields in all instances of squamous cell tumours that were eventually found. It has been suggested than eventual manifestation of the primary site adversely affects prognosis, which is in agreement with our results.

Adult↗
PubMed1996

Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion.

E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell-cell adhesion and plays an important role in maintaining the normal phenotype of epithelial cells. Disruption of E-cadherin activity in epithelial cells correlates with formation of metastatic tumors. Decreased adhesive function may be implemented in a number of ways including: (a) decreased expression of E-cadherin; (b) mutations in the gene encoding E-cadherin; or (c) mutations in the genes that encode the catenins, proteins that link the cadherins to the cytoskeleton and are essential for cadherin mediated cell-cell adhesion. In this study, we explored the possibility that inappropriate expression of a nonepithelial cadherin by an epithelial cell might also result in disruption of cell-cell adhesion. We showed that a squamous cell carcinoma-derived cell line expressed N-cadherin and displayed a scattered fibroblastic phenotype along with decreased expression of E- and P-cadherin. Transfection of this cell line with antisense N-cadherin resulted in reversion to a normal-appearing squamous epithelial cell with increased E- and P-cadherin expression. In addition, transfection of a normal-appearing squamous epithelial cell line with N-cadherin resulted in downregulation of both E- and P-cadherin and a scattered fibroblastic phenotype. In all cases, the levels of expression of N-cadherin and E-cadherin were inversely related to one another. In addition, we showed that some squamous cell carcinomas expressed N-cadherin in situ and those tumors expressing N-cadherin were invasive. These studies led us to propose a novel mechanism for tumorigenesis in squamous epithelial cells; i.e., inadvertent expression of a nonepithelial cadherin.

Cadherins↗
PubMed1996

Elevated arginine vasopressin levels in squamous cell cancer of the head and neck.

The reported effectiveness of single tumor markers (TMs) associated with squamous cell cancer of the head and neck ranges from 15% to 71%, with most studies reporting sensitivity no higher than 50%. An increased incidence of the syndrome of inappropriate secretion of antidiuretic hormone or arginine vasopressin (SIADH) in patients with head and neck cancer has been reported. Serum arginine vasopressin (AVP) was studied as a possible TM in these patients. Sixty-three patients with squamous cell carcinoma of the head and neck determined as potentially curable were prospectively evaluated before treatment and compared to 17 patients with apparent cure of head and neck squamous cell cancer who served as controls. Serum AVP levels were obtained and determined by radioimmunoassay in the preoperative period and 1 week postoperatively in 15 patients. Thirty-four patients were staged as T4, 26 as T3, and 3 as T2. Twenty-one (33%) of the 63 patients had no neck involvement. Twenty-four (38%) of 63 patients had elevated serum AVP levels corrected for serum osmolarity. Of the 15 patients evaluated before and after surgery, 8 (53%) had elevated serum AVP levels preoperatively. Of these 8 patients, 3 had reduction in AVP levels and 5 had complete normalization after 1 week. The result obtained for serum AVP do not exceed results of other TMs reported. AVP may also not be as specific as other TMs for cancer of the head and neck. Our group with AVP sampled postoperatively is too small for us to draw conclusions, but reduction of its levels after treatment in all patients may be significant. These preliminary results indicate that further evaluation of AVP during the posttreatment course in a larger number of cases, and perhaps with other TMs as well, is warranted.

Adult↗
PubMed1996

Recurrence of head and neck cancer after surgery or irradiation: prospective comparison of 2-deoxy-2-[F-18]fluoro-D-glucose PET and MR imaging diagnoses.

PURPOSE: To evaluate the diagnostic accuracy of positron emission tomography (PET) with administration of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) relative to that of magnetic resonance (MR) imaging and/or computed tomography (CT) in recurrent head and neck cancers. MATERIALS AND METHODS: Twelve adult patients (mean age, 63 years) with previously treated head and neck cancers and clinical suspicion of recurrence underwent FDG PET and MR imaging and/or CT. All images were blindly and independently interpreted without histopathologic findings (obtained within 1 week of imaging). The level of confidence in image interpretation was graded by using a five-point rating system (0 = definitely no recurrence to 4 = definite recurrence). RESULTS: Recurrence was confirmed in eight patients. With a rating of 4 as a positive finding, FDG PET yielded a sensitivity and specificity of 88% (seven of eight) and 100% (four of four), respectively; MR imaging and/or CT, 25% (two of eight) and 75% (three of four), respectively. Receiver-operating characteristic analysis showed significantly better diagnostic accuracy with FDG PET than with MR imaging and/or CT (area under curve = 0.96 vs 0.55, P < .03). CONCLUSION: These data indicate that PET metabolic imaging, as compared with anatomic methods, has improved diagnostic accuracy for recurrent head and neck cancer.

Aged↗
PubMed1996

Chemotherapy followed by accelerated fractionated radiation for larynx preservation in patients with advanced laryngeal cancer.

PURPOSE: Larynx preservation in advanced, resectable laryngeal cancer may be achieved using induction chemotherapy (CT) followed in responding patients by definitive radiation (RT). To address potential accelerated repopulation of clonogenic tumor cells during the prolonged total treatment time, we studied the feasibility of accelerated fractionated RT after CT. METHODS: Patients with advanced laryngeal cancer received two cycles of cisplatin 100 mg/m2 and fluorouracil (5-Fu) 1,000 mg/m2/d for 5 days. Responding patients received a third cycle after which those who had complete response or tumor down-staging to T1 proceeded with accelerated RT: 70.4 Gy delivered over 5.5 weeks. Patients who achieved a lesser response to CT underwent total laryngectomy and postoperative RT. RESULTS: Thirty-three patients were accrued. Three died during the course of CT and two declined definitive treatment after CT. Twenty-one patients had a major response to CT, 20 of whom received accelerated RT. Median weight loss during RT was 11%. Late severe morbidity was observed in five patients (25%). All four patients who underwent salvage laryngectomy after accelerated RT experienced major postoperative complications. The locoregional failure rate was 25%. The larynx was preserved in 48% of the total study population and in 80% of the patients irradiated according to the study protocol. CONCLUSION: Accelerated RT after CT as delivered in this study may increase both acute and long-term morbidity rates compared with studies using standard RT after CT. It did not seem to improve local/regional tumor control or survival despite stringent patient selection criteria.

Adult↗
PubMed1995

Increase in suprabasilar integrin adhesion molecule expression in human epidermal neoplasms accompanies increased proliferation occurring with immortalization and tumor progression.

In a previous prospective study of 80 patients with squamous cell carcinoma of the upper aerodigestive tract, a progressive increase in expression of the integrin cell adhesion molecule alpha 6 beta 4 in suprabasilar cell layers of the tumor parenchyma was associated with an increase in early recurrence after therapy. In this study, we determined the relationship of the altered expression pattern of the integrin to changes occurring during benign, invasive, or metastatic stages of tumor development. Suprabasilar expression of integrin alpha 6 beta 4 appeared with neoplastic transformation in benign squamous papillomas, but homogeneous expression occurred more frequently in the parenchyma of primary and metastatic squamous cell carcinomas. The variation in the extent of suprabasilar integrin expression among the tumors corresponded to the variation in the population undergoing proliferation as determined by two independent markers of proliferation. Integrin expression was quantified in primary, HPV 16 DNA-immortalized, and v-ki-ras oncogene-transformed keratinocytes, and the pattern of expression was compared with cell cycle progression. Primary keratinocyte lines showed a bimodal distribution of integrin expression, with one population showing decreased integrin expression, cell size, and a block of cell cycle progression consistent with differentiation, whereas another population exhibited high integrin expression and full progression through the cell cycle, consistent with proliferation. HPV-immortalized and v-ki-ras-transformed cell lines undergoing continuous proliferation exhibited uniformly strong integrin expression, which was similar in intensity to that observed in the proliferating population of normal keratinocytes. Similar increases in expression of two additional integrins, alpha 2 beta 1 and alpha 3 beta 1, occurred along with integrin alpha 6 beta 4 in tissue specimens and cell lines derived from neoplasms. Thus, epidermal neoplasms display an increase in a population of cells exhibiting constitutive expression of a repertoire of integrins, which is similar to that found transiently in the acute phase of epidermal wound healing, a physiological response in which hyperproliferation, retention of multiple layers of proliferating cells, and migration occur. The association of a progressive increase in suprabasilar expression of these integrins with early tumor recurrence and advanced neoplasia suggests that constitutive expression and function of the same repertoire of integrins may be advantageous, rather than sufficient, for tumor progression.

Antigens, Surface↗
PubMed1995

Surgery after organ preservation therapy. Analysis of wound complications.

OBJECTIVE: To determine the incidence and risk factors for the development of major wound complications in patients with squamous cell cancer of the head and neck that require surgical salvage after an initial treatment regimen of induction chemotherapy and definitive radiation therapy for organ preservation. DESIGN: Retrospective survey. SETTING: Academic tertiary care referral center. PATIENTS AND INTERVENTION: The medical records of 96 patients treated with induction chemotherapy followed by definitive radiation therapy were reviewed; 18 of these patients requiring a surgical salvage procedure after completing chemotherapy and radiation therapy and these constituted the study group. MAIN OUTCOME MEASURES: Major wound complications. RESULTS: Major wound complications occurred in 11 (61%) of the 18 patients. Surgical salvage within 1 year of initial treatment had a 77% incidence of major wound complications vs a 20% incidence if performed 1 year after initial treatment. The mean time to resolution of fistulae and flap necrosis was 7.7 months. Two deaths were attributed to major wound complications: one patient had a carotid blowout; one had postoperative pneumonia. CONCLUSIONS: Salvage surgical procedures performed after induction chemotherapy and definitive radiation therapy have a high rate of major wound complications. This should be considered when assessing organ preservation treatment strategies.

Carcinoma, Squamous Cell↗