[Immunocorrection in the treatment of diffuse peritonitis in aged patients].

The results of treatment of 161 patients with diffuse forms of peritonitis with, using of the immunostimulators are analyzed. The algorithm of staged complex immunocorrection for patients with acute pancreatitis, including aged patients, is worked out. The use of it improves the results of treatment and allows decrease the morbidity.

[Prediction of surgical infections severity at elderly and old patients].

Clinical and immunological characteristics of generalized peritonitis in different age group at complicated and non-complicated postoperative period were analyzed at 246 patients with abdominal purulent infection. Prognostic criteria of complicated postoperative period at elderly and old patients have been determined. It is concluded that interpretation of immune characteristics permits to determine the prognostic criteria of disease course and outcome at various age group, and to use the rational immunocorrection.

Molecular differences in mucoepidermoid carcinoma and adenoid cystic carcinoma of the major salivary glands.

OBJECTIVE/HYPOTHESIS: Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), the most common malignancies of the major salivary glands, are clinically and pathologically different. To determine whether MEC and ACC have different molecular characteristics, we examined the expression of erbB-2, erbB-3, epidermal growth factor receptor (EGFR), and transforming growth factor-alpha (TGF-alpha), important molecular features in other malignancies. STUDY DESIGN/METHODS: Archival tissue sections of 22 MEC and 6 ACC tumors of the major salivary glands were evaluated immunohistochemically for expression of erbB-2, erbB-3, EGRF, and TGF-alpha. A differential immunostaining score, reflecting the difference in immunostaining between carcinoma and uninvolved salivary gland tissue, was calculated for cytoplasmic and membranous staining. RESULTS: Positive immunostaining for all biomarkers was observed in the cytoplasm and membrane of both tumors. However, expression was higher in MEC than in ACC tumors and was statistically significant for cytoplasmic EGFR (P =.009), TGF-alpha (P =.041), and membranous EGFR (P =.004). A significantly higher percentage of MEC cells also demonstrated positive immunostaining for cytoplasmic erbB-3 (P =.022), EGFR (P =.005), membranous erbB-3 (P =.022), and EGFR (P =.013). The differential immunostaining score was significantly higher for MEC compared with uninvolved alveolar tissue and the membranes of uninvolved ductal tissue. There were no statistically positive differential immunostaining scores for ACC. CONCLUSIONS: There is a clear difference in the molecular phenotypes of MEC and ACC. The lack of statistically significant expression in ACC, when compared with similar uninvolved salivary gland tissue, suggests minimal involvement for these molecular structures in the pathogenesis of ACC. Conversely, erbB-2, erbB-3, EGFR, and TGF-alpha may have a role in the development and progression of MEC. These results have therapeutic implications for MEC of the major salivary glands.

Bupropion-induced erythema multiforme.

The high rate of dermatologic adverse effects associated with bupropion use may extend to its sustained-release preparation, currently prescribed extensively for smoking cessation as well as for treatment of depressive conditions. We report what we believe to be the first case, in a 31-year-old woman, of erythema multiforme after administration of sustained-release bupropion (Wellbutrin SR) for treatment of depression. This report emphasizes that prescribers must aggressively follow up their patients who have rashes or urticaria, discontinuing the medication as soon as erythema multiforme is suspected and watching closely for the emergence of potentially life-threatening dermatologic conditions.

Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers.

PURPOSE: Epidermal growth factor receptor (EGFr) is overexpressed in a majority of head and neck squamous cell carcinomas, and this overexpression is associated with a poor prognosis. Therefore, EGFr has become the target of investigations aimed at disabling the receptor to determine whether this process leads to improved tumor kill with conventional treatment. MATERIALS AND METHODS: C225 is an anti-EGFr monoclonal antibody that inhibits receptor activity by blocking the ligand binding site. A panel of human head and neck squamous cell carcinoma cell lines was used to study the combination of C225 and radiation. RESULTS: It was determined that the combination of C225 (5 microgram/mL) delivered simultaneously with radiation (3 Gy) resulted in a greater decrement in cellular proliferation than either treatment alone. This reduction in proliferation correlated with reduced EGFr tyrosine phosphorylation and a reduction in phosphorylated signal transducer and activator of transcription-3 (STAT-3) protein (known to protect cells from apoptosis). Also, the decrement in proliferation correlated with increased apoptotic events, thereby indirectly linking C225/radiation-induced regulation of STAT-3 protein to apoptosis. CONCLUSION: This preclinical work serves as important support for the ongoing clinical investigation of C225 and radiotherapy for patients with head and neck carcinomas. The initial results of these clinical studies have been promising.

Selective gene delivery to head and neck cancer cells via an integrin targeted adenoviral vector.

In vivo cancer gene therapy approaches for squamous cell carcinoma of the head and neck (SCCHN) based on adenoviral vector-mediated gene delivery have been limited by the suboptimal efficacy of gene transfer to tumor cells. We hypothesized that this issue was due to deficiency of the primary adenoviral receptor, the coxsackie-adenovirus receptor (CAR), on the tumor targets. Studies of CAR levels on SCCHN cell lines confirmed that their relative refractoriness to the adenoviral vector was based on this deficiency. To circumvent this deficiency, we applied an adenoviral vector targeted to a tumor cell marker characteristic of SCCHN. In this regard, integrins of the alpha2beta1 and alpha3beta1 class are frequently overexpressed in SCCHN. Furthermore, these integrins recognize the RGD peptide motif. On this basis, we applied an adenoviral vector genetically modified to contain such a peptide within the HI loop of the fiber protein as a means to alter viral tropism. Studies confirmed that the CAR-independent gene delivery achieved via this strategy allowed enhanced gene transfer efficiencies to SCCHN tumor cells. Importantly, this strategy could achieve preferential augmentation of gene transfer in tumor cells compared with normal cells. The ability to achieve enhanced and specific gene transfer to tumor cells via adenoviral vectors has important implications for gene therapy strategies for SCCHN and for other neoplasms in general.

Retargeting to EGFR enhances adenovirus infection efficiency of squamous cell carcinoma.

BACKGROUND: Adenovirus-mediated gene therapy has been used for squamous cell carcinoma of the head and neck (SCCHN), but the in vivo efficacy has been limited by a lack of tissue specificity and low infection efficiency. We are interested in improving cancer gene therapy strategies using targeted adenovirus vectors. OBJECTIVE: To determine if the infection efficiency of adenovirus-mediated gene transfer to SCCHN cells could be enhanced by retargeting to the epidermal growth factor receptor (EGFR), which is known to be overexpressed in these tumors. DESIGN: Epidermal growth factor receptor retargeting in SCCHN cells was accomplished with a bispecific antibody that recognized the knob domain of adenovirus as well as EGFR. Using this retargeting schema, we compared the infection efficiency and specificity of unmodified and EGFR-retargeted adenovirus. RESULTS: Squamous cell carcinoma of the head and neck cell lines were shown to be infected by adenovirus with low efficiency, which is likely because of the low level of adenovirus receptor expressed in the SCCHN cells. Epidermal growth factor receptor retargeting markedly enhanced transduction in both SCCHN cell lines and primary tumor tissue, as indicated by the elevated levels of reporter gene expression. Furthermore, retargeting enhanced infection of tumor tissue compared with normal tissue from the same patient. CONCLUSIONS: Epidermal growth factor receptor retargeting enhanced adenovirus infection of SCCHN cells and, in doing so, augments the potency of the vector. This modification makes the vector potentially more valuable in the clinical setting.

Fatty acid synthase expression is increased in neoplastic lesions of the oral tongue.

BACKGROUND: Fatty acid synthase (FASE) is required for fatty acid synthesis. Elevated levels of FASE have been observed in a variety of malignancies. METHODS: We examined the expression of FASE in 56 primary squamous cell carcinomas (SCC) of the tongue using immunohistochemistry (IHC) with a monoclonal antibody to FASE. RESULTS: Immunoreactivity was low in histologically normal epithelium (0.42 +/- .07, n = 43), moderate in mildly dysplastic epithelium (1.41 +/- 11, n = 40), and strong in SCC of the tongue (1.64 +/- 10, n = 50). Both mild dysplasia and SCC stained more strongly than histologically normal epithelium (p<0.00001). Well-differentiated tumors showed increased immunoreactivity when compared to less well-differentiated tumors (p=0.044). Decreased overall survival was observed among patients with tumors with low immunoreactivity (p = 0.04). CONCLUSIONS: Increased expression of FASE in dysplasia and squamous carcinomas of the oral tongue may be an indicator of both differentiation and early neoplastic change. FASE expression may be useful diagnostically, prognostically, and as a potential target for therapy.

T1 and T2 squamous cell carcinoma of the oral tongue: prognostic factors and the role of elective lymph node dissection.

BACKGROUND: The management of micrometastatic disease from squamous cell carcinoma (SCC) of the oral tongue remains controversial. This study describes prognostic factors in the disease and reviews the role of elective neck dissection (END). METHODS: A retrospective analysis of all patients undergoing definitive surgical treatment of T1 and T2 SCC of the oral tongue between 1956 and 1994 at the University of Alabama at Birmingham was performed. RESULTS: Patient, disease, and treatment variables were compiled for 169 patients. Multivariate analysis showed age (p = .02), sex (p = .02), disease differentiation (p = .0003), and palpable lymphadenopathy (p = .02) to be significant prognostic variables. Fifteen patients underwent END and 6 were shown to have micrometastatic disease (40.0%). There were no neck recurrences in these patients, but END was not shown to improve survival. CONCLUSIONS: The presence of poorly differentiated disease gave the worst prognosis in this population of patients with T1 and T2 SCC of the oral tongue. A high incidence of nodal micrometastatic disease and the absence of recurrent disease after END suggest that END is appropriate therapy for these patients.

Concomitant chemotherapy and reirradiation as management for recurrent cancer of the head and neck.

Thirty-five patients with inoperable recurrent head and neck cancer previously treated with definitive irradiation were treated with reirradiation and concomitant chemotherapy. Patient records were retrospectively reviewed to assess toxicity, response, and survival. Patients received one of three regimens: 1) 40 Gy total (2 Gy daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 2 g hydroxyurea orally daily for 5 days; 2) 48 Gy total (1.2 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days; 3) 60 Gy total (1.5 Gy twice daily), 300 mg/m2 5-fluorouracil intravenous bolus, and 1.5 g hydroxyurea orally daily for 5 days. For all regimens, treatment was given only on weeks 1, 3, 5, and 7. Acute toxicity was mainly hematologic and was less severe with the lower hydroxyurea dose. Acute mucosal and skin toxicity was acceptable for all regimens. Late toxicity was noted in 4 of 17 patients who survived 12 months or more. Late effects were Radiation Therapy Oncology Group grade 3 or less. Fifteen of 35 patients achieved a complete response, and 11 of 35 patients achieved a partial response. The median survival rate was 10.5 months. There was no significant difference in responses or median survival between the groups. Reirradiation of head and neck cancer with 5-fluorouracil and hydroxyurea offers acceptable acute toxicity and minimal late effects. The clinical response rates and median survival are encouraging. Further investigation is warranted.

Nasal inverted papilloma with involvement of middle ear and mastoid.

Inverted papillomas of the paranasal sinuses have been characterized by their unusually benign histologic features, their ability to grow rapidly with bony destruction, and their tendency to recur if not adequately treated. The association of inverted papilloma with squamous cell carcinoma is well described, but malignant transformation is relatively rare. We report a case of a multiply recurrent inverted papilloma that spread to the middle ear and mastoid and eventually underwent malignant transformation with skull base invasion. Pathologic examination demonstrated many of the characteristics associated with malignant transformation. In addition, progesterone receptors were demonstrated that may have stimulated this tumor during the patient's pregnancy. To our knowledge, no similar cases have been reported in the literature.

Aneurysmal bone cyst of the zygomatic arch.

BACKGROUND: Aneurysmal bone cysts are rare vascular lesions that are most commonly found in the long bones. They are rare in the head and neck. Only two prior cases of aneurysmal bone cysts of the zygoma have been reported in the world literature. RESULTS: We report a case of aneurysmal bone cyst arising in the zygomatic arch with intracranial extension treated with selective arterial embolization and complete excision via an intratemporal fossa approach. This is the first such case reported in the head and neck surgery literature. CONCLUSIONS: Selected cases of aneurysmal bone cyst may be safely treated with selective arterial embolization and complete resection.

Paragangliomas of the neck.

Between 1967 and 1990 inclusive, 28 patients with paragangliomas of the neck were diagnosed at the University of Alabama at Birmingham Affiliated Hospitals. There were 11 men and 17 women, whose ages ranged from 12 to 76 years (mean, 47 years). Tumor locations included the carotid bodies (19 cases), the vagus nerves (three), supraglottic larynx (two), the left lateral pharyngeal wall (one), posterior to the right jugular vein (not otherwise defined) (one), subcutaneous neck tissue (one), and a cervical lymph node with unknown primary (one). Diagnostic workup included angiography (23 cases) with preoperative embolization (three), computed tomography (one), magnetic resonance imaging (two), and urinary catecholamine assay (four). All 28 patients underwent resection of the lesions. Cranial nerve damage occurred in 11 patients (39%). There were no perioperative deaths or cerebrovascular accidents, although one of two saphenous vein grafts became thrombotic after carotid body tumor resection.

A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high-dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day x 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies.

Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation.

Head and neck cancer locally recurrent after previous irradiation and surgery presents a difficult management problem. Conventional treatment alternatives include chemotherapy, reirradiation with interstitial implant, and hyperthermia. Reirradiation with external beam is generally not considered because of previous high radiation dose and limited tissue tolerance. In this study, 21 patients with recurrent and previously irradiated head and neck cancer were treated in a Phase I-II fashion. Patients received 5 days of 5-fluorouracil, 300 mg/m2/day IV bolus, Hydroxyurea 1.5 or 2 g/day by mouth and external beam radiation therapy every 2 weeks for up to four courses. Of 20 evaluable patients, 9 have attained a complete response (CR) and 6 a partial response (PR). Fifteen patients completed all planned therapy, eight on time, seven patients with delays. With a median follow-up of 7 months, 13 patients are alive, 7 disease-free (3 after salvage surgery) and 6 with recurrence. Eight patients have died. The 1-year survival is 56%. Treatment toxicity was mainly neutropenia. No major early or late radiation related side effects have been observed at a median follow-up of 7 months. Neither previous radiation dose, time since first radiation, prior chemotherapy, or site of recurrence was predictive of response or treatment tolerance. Patients with a performance status of at least 80 had a significant higher CR rate, with 7/10 patients in this group, as compared to 2/10 patients in patients with a performance status less than 80, achieving a CR. Reirradiation with 5-fluorouracil and hydroxyurea is a well tolerated outpatient treatment program for patients with recurrent and previous irradiated head and neck cancer that produces a high response rate and can provide significant palliation of symptoms.

Predicting radioresistance in early glottic squamous cell carcinoma by DNA content.

Nuclear DNA content has been implicated as a prognostic factor in an increasing number of tumor types. Current data on the role of DNA content in head and neck carcinoma are conflicting and incomplete. To evaluate the role of DNA content in predicting radioresistance, 29 patients with T1N0M0 squamous cell carcinoma of the glottic larynx who had undergone uniform curative radiotherapy and whose clinical outcome was known had flow cytometric analysis for DNA content performed on their tumors with paraffin-embedded archival tissues. Five aneuploid lesions and 24 diploid lesions were identified. All aneuploid lesions occurred in radioresistant tumors. The probability of an aneuploid tumor failing radiotherapy was highly significant at p = .016. No DNA discordance was found in a sampling of half of the radioresistant lesions' pretreatment and recurrent specimens, for a 100% predictive value of moderate statistical power. On the basis of these findings, patients with aneuploid T1 glottic lesions should be referred for primary surgical therapy.

A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation therapy in patients with squamous cell cancer of the head and neck.

The radiosensitization properties of 5-FU are well documented, and clinical trials have suggested improved local control and survival in head and neck cancer. Clinical trials to date have used bolus injection or short term (less than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant with conventional radiation therapy, 18 patients with advanced inoperable head and neck cancers were treated with conventional irradiation and 100, 200, 250, or 300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum tolerated dose and is recommended for Phase II studies.