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Biomedical subjects

C H Snyderman

Publications and source records attributed to C H Snyderman.

At least 19 recordsLinked to original sources

Inhibition of growth of a murine squamous cell carcinoma by a cyclooxygenase inhibitor increases leukotriene B4 production.

OBJECTIVE: To determine the role of metabolites of arachidonic acid in the growth of squamous cell carcinomas of the head and neck. DESIGN: Investigation of the effect of a cyclooxygenase inhibitor, piroxicam, on the growth of squamous cell carcinoma in a murine model. INTERVENTION: C3H/HeJ mice bearing squamous cell carcinoma (SCCVII) were treated with piroxicam (0.08 mg/d, orally) for 30 days beginning 1 day before tumor inoculation. MAIN OUTCOME MEASURES: Decrease in tumor volumes and tumor growth rates. RESULTS: Significant inhibition of tumor growth (P = .002) and final tumor weight (P = .0007) was noted in the group receiving piroxicam therapy. Prostaglandin E2 levels in the tumor tissue were unrelated to treatment or tumor size. Increased levels of leukotriene B4 were observed in the piroxicam-treated group (P = .03), and larger tumors were associated with decreased leukotriene B4 levels (P = .0001). CONCLUSIONS: Cyclooxygenase inhibitors may be effective in the treatment of some squamous cell carcinomas. The therapeutic effect of cyclooxygenase inhibitors may result from shunting into the lipoxygenase pathway of arachidonic acid metabolism.

Animals

A reappraisal of the squamous cell carcinoma antigen as a tumor marker in head and neck cancer.

OBJECTIVE: To analyze serial measurements of squamous cell carcinoma antigen (SCCAg) to determine its prognostic significance in squamous cell carcinoma of the head and neck (SCCHN). DESIGN: Retrospective analysis of serial SCCAg measurements in 75 patients with squamous cell carcinoma of the head and neck. Serum samples were obtained preoperatively and at postoperative intervals ranging from 1 week to 36 months. Serum SCCAg levels were determined by radioimmunoassay. SETTING: Oncologic head and neck practice at a tertiary referral hospital. PATIENTS: Tumor Registry data of 75 consecutive patients with at least three postoperative SCCAg determinations were reviewed to provide equal numbers of patients with and without recurrent disease. All patients who remained disease-free were followed up for at least 2 years. All patients were previously untreated and underwent surgical therapy. MAIN OUTCOME MEASURES: Association of postoperative SCCAg levels and 2-year disease-free survival. RESULTS: No differences in preoperative levels were noted, but SCCAg levels predicted 2-year disease-free survival at 6, 9, and 12 months after surgery. The ratio of post-operative SCCAg levels to preoperative and early post-operative levels also provided prognostic information. CONCLUSIONS: Serial measurements of SCCAg postoperatively in patients with head and neck cancer predict outcome and may allow for earlier detection of recurrent disease. Further studies are needed to determine if earlier detection can be translated into improved survival.

Antigens, Neoplasm

Superiority of the T and N integer score (TANIS) staging system for squamous cell carcinoma of the oral cavity.

An alternative to the TNM classification system has been proposed for patients with head and neck cancer. The T and N integer score (TANIS) system adds the integer values of T and N classifications. The TNM and TANIS staging systems were retrospectively evaluated for 186 patients with squamous cell carcinoma of the oral cavity (tongue and floor of mouth). The TANIS system was found to better separate the patients into prognostic groups and allowed a more accurate prediction of disease-free survival.

Carcinoma, Squamous Cell

Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.

The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Prognostic significance of prostaglandin E2 production by mononuclear cells and tumor cells in squamous cell carcinomas of the head and neck.

Prostaglandin E2 (PGE2) has been implicated as a cause of immunosuppression in patients with head and neck cancer. To determine the relative contribution of tumor cells and mononuclear cells to PGE2 levels in vivo, tumor cells and tumor-infiltrating mononuclear cells (TIMC) were isolated from fresh tumor biopsy specimens of 23 patients with squamous cell carcinoma of the head and neck (SCCHN) by using enzymatic digestion and differential gradient centrifugation. Peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) from metastatic and nonmetastatic lymph nodes were also isolated. Cell fractions were cultured for 24 hours, and PGE2 levels of supernatant were determined by radioimmunoassay. PGE2 production by LNMC was significantly decreased compared to tumor cells, TIMC, and PBMC (P = .0002). LNMC from metastatic lymph nodes produced significantly higher levels of PGE2 (P = .02) compared to nonmetastatic lymph nodes. Although T stage was not correlated with PGE2 production by TIMC or tumor cells, advanced N stage (N1-3) was associated with decreased PGE2 production by TIMC (P = .006). These results suggest that both tumor cells and TIMC are sources of PGE2 in tumor tissues of patients with SCCHN and that decreased PGE2 production by host inflammatory cells may have clinical significance in the development of cervical metastases.

Adult

Laryngotracheal separation for intractable aspiration: a retrospective review of 34 patients.

LTS is an effective surgical procedure that results in the elimination of intractable aspiration. Most of these patients have major neurologic impairment due to progressive neurologic disease or devastating injury secondary to stroke, trauma, or surgery. The procedure can be performed in ill, debilitated patients and is well tolerated, even with local anesthesia. Few patients lose communicative speech, and some patients gain the ability to swallow following the procedure. LTS should be considered in the management of patients with intractable aspiration before performance of a tracheotomy because the procedure is technically easier to perform at this time and may reduce the risk of a wound-healing complication. Postoperative nursing care is decreased, and most patients can be discharged or transferred to a chronic-care facility within 2 to 3 weeks following the procedure.

Adult

Role of skull base surgery for local control of sarcoma of the nasal cavity and paranasal sinuses.

Sarcomas of the nose and paranasal sinuses are rare neoplasms and comprise less than 1% of the malignancies arising in the sinonasal tract. From 1977 to 1989, we had the opportunity to treat 15 patients presenting with these tumors at The Eye & Ear Institute of the University of Pittsburgh. The clinical charts of these patients were reviewed retrospectively for demographic data, characteristics of disease, treatment considerations and clinical outcome. Data were also analyzed with special attention to the role of skull base surgery for the local control of tumors. Seven patients underwent cranial base surgery as part of their original therapy. Two of these patients are alive with no evidence of disease, one patient died of other causes, and four are dead of disease. Two patients died with local disease. Although not statistically significant due to the small number of patients, these data suggest that cranial base surgery can improve the local control of sarcomas of the sinonasal tract that approach or invade the skull base.

Adolescent

Angiogenesis induced by head and neck squamous cell carcinoma xenografts in the chick embryo chorioallantoic membrane model.

The angiogenic potential of head and neck tumors compared to nonneoplastic control tissues was investigated by using the chick embryo chorioallantoic membrane (CAM) as a bioassay for angiogenesis. Eighty tumor specimens from 10 patients with squamous cell carcinoma of the head and neck were grafted onto the CAM of 7-day chick embryos. The presence of tumor in the original explant was confirmed histologically. Forty-four embryos (55%) survived and were evaluated histologically at day 17. Tumors were growing on or invading the CAM mesoderm in 30 of 44 embryos (68%). Before harvesting of the membranes, the tumors and surrounding blood vessels were photographed, and the angiogenic responses were graded by a panel of blinded observers. Tumor explants elicited a significantly greater angiogenic response than nontumor controls (p = .01). We conclude that head and neck squamous cell carcinomas can induce an angiogenic response in vivo, presumably secondary to the production of an unidentified angiogenic factor, and that the chick embryo CAM is an effective model for quantifying angiogenesis induced by head and neck tumors.

Allantois

Postoperative wound infection. A poor prognostic sign for patients with head and neck cancer.

BACKGROUND: The development of a wound infection has been identified as a favorable prognostic factor after oncologic surgical procedures. METHODS: The authors retrospectively studied the relationship between postoperative wound infection, local/regional tumor recurrence, and survival rates in 134 patients undergoing therapeutic surgical resection for squamous cell carcinoma of the head and neck (SCCHN). RESULTS: The median age was 61 years (range, 25-87 years) with most (75%) patients having advanced disease (Stage III or IV). Patients without evidence of recurrent disease were followed up for a median time of 34 months (range, 24-68 months). Twenty-nine (22%) had local or regional bacterial infections develop postoperatively. Recurrence rates were increased (P = 0.008) in patients with postoperative wound infections compared with patients who had distant infections, e.g., pneumonia or urinary tract infection, or no infection. Disease-free survival also was adversely affected (P = 0.04) in this group. Both advanced tumor stage and postoperative wound infections were independently associated with decreased survival, with odds ratios of 2:3 and 2:4, respectively. CONCLUSIONS: These data contrast with other reports in the literature of a beneficial effect of postoperative wound infection on outcome. These findings suggest a possible relationship between local/regional immune function and postoperative infection in patients with SCCHN:

Adult

Experimental tracheal replacement using a revascularized jejunal autograft with an implantable Dacron mesh tube.

Defects comprising more than 50% of the trachea cannot be reliably reconstructed by any current technique or prosthesis. A composite tracheal replacement implant consisting of a Dacron-urethane mesh tube and revascularized jejunal autograft was applied to this problem. This composite implant was used to replace 7 to 10 cm of trachea in eight dogs. The implant was sewn to the outside (serosal surface) of the jejunum to provide permanent structural support to the autograft, and an intraluminal silicone tube was placed inside the jejunal segment and left for 4 weeks following reconstruction. Six of eight animals survived the predetermined time periods and were killed painlessly in groups of two animals at 1, 2, and 6 months after removal of the intraluminal silicone tube. Postoperative intubation, ventilation, or tracheostomy was not necessary. Excessive secretions were not seen in any of the animals, and a fair to good performance status was maintained until death in all but one animal. Histologic examination revealed slight thinning of the jejunal mucosa, with no change in the jejunal muscularis. These data suggest that with further refinement this composite implant may be a viable reconstructive option in humans.

Animals

Functional and phenotypic analysis of lymphocytes in head and neck cancer.

We compared the phenotype and antitumor effector function of lymphocytes obtained from tumor tissues, lymph nodes, and the peripheral blood of patients with head and neck cancer. Freshly isolated tumor-infiltrating lymphocytes were deficient in CD4+ T cells in comparison with lymph node lymphocytes (LNL) and peripheral blood lymphocytes. A significantly higher CD4/CD8 ratio observed in LNL vs tumor-infiltrating lymphocytes and peripheral blood lymphocytes was attributable to both a significant enrichment in CD4+ T cells as well as a decrease in CD8+ T cells. The percentage of natural killer cells (CD3-CD56+) was uniformly low in both tumor-infiltrating lymphocytes and LNL. In patients with cervical metastases, LNL contained an increased proportion of CD16+ cells. Tumor-involved lymph nodes were not enriched in the CD8+C11b+ subset of T "suppressor" lymphocytes compared with uninvolved lymph nodes. Also, tumor-involved lymph nodes had significantly fewer CD4+ T cells than did uninvolved lymph nodes. In comparison with peripheral blood lymphocytes, freshly isolated tumor-infiltrating lymphocytes and LNL were depleted of cytotoxic effector cells, as indicated by low or absent cytotoxic activity against tumor cell targets. The ability to generate lymphokine-activated killer cells was significantly reduced in LNL in comparison with peripheral blood lymphocytes. In patients with head and neck cancer, depressed local and regional antitumor responses are associated with a deficiency of functional cytotoxic effector cells rather than an increase in suppressor T lymphocytes.

Adult

Computerized tomography and magnetic resonance imaging following cranial base surgery.

The computed tomography scans and magnetic resonance imaging films of 57 patients who underwent anterior or anterolateral cranial base surgery from January 1987 to August 1989 were retrospectively reviewed to ascertain the significance of early and late postoperative intracranial imaging changes. Extra-axial changes (air, blood, cerebrospinal fluid collection) were found in 96% of patients; axial changes (brain edema, contusion) were seen in 30% of patients in the first postoperative period (72 hours). Subsequently, extra-axial changes began to resolve but axial changes became more prevalent. After 6 months, only axial changes persisted (encephalomalacia). It was encouraging to find a low correlation of imaging abnormalities with clinically significant findings.

Encephalomalacia

Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine-activated killer cells and interleukin 2.

The efficacy of local adoptive immunotherapy with human lymphokine-activated killer cells and recombinant interleukin 2 (rIL-2) in growth inhibition of established squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a nude mouse model. The model of xenografted SCCHN was established by s.c. injections of in vitro maintained tumor cells (2-10 x 10(6) cells/mouse) into the flank of splenectomized animals pretreated with cyclophosphamide (200 mg/kg). The SCCHN line used was tumorigenic in 95% of the appropriately conditioned nude mice. Inhibition of tumor growth by locally administered effector cells was the end point of the study, since the tumors did not metastasize within 6 weeks of tumor challenge. Either i.p. or local administration of rIL-2 alone (1000 units/day) to the tumor site daily for 2 weeks resulted in a significant inhibition of tumor growth. In the absence of detectable natural killer activity in these mice, a modest dose of rIL-2 had a direct antitumor effect on SCCHN cells in vivo. In addition, complete inhibition of tumor growth was achieved with 3 times weekly injections of 5-10 x 10(6) lymphokine-activated killer cells delivered to the tumor site and 1000 units of rIL-2 administered locally every day for 2 weeks. Our data indicate that local or systemic immunotherapy with rIL-2 alone or local adoptive immunotherapy with an adequate dose of lymphokine-activated killer cells plus rIL-2 may be effective in preventing the growth of established SCCHN tumors in vivo.

Animals

Anterior cranial base reconstruction: role of galeal and pericranial flaps.

Reconstruction of surgical defects in 30 patients undergoing surgery of the anterior cranial base was performed using pericranial, galeopericranial, and galeal scalp flaps. Twenty-seven patients had resection of neoplasms, the majority of which were malignant. Fifty-seven percent of patients received prior therapy consisting of surgery and/or radiotherapy. Adequate healing of the cranial base was noted in all cases without persistent cerebrospinal fluid leaks, meningitis, or brain herniation. Mucosalization of the intranasal surface was noted. No skin grafts were used. At a median follow-up of 13 months, 67% of patients were alive with no evidence of disease. The pericranial, galeopericranial, and galeal flaps are highly reliable, versatile, and well suited for reconstruction of the anterior cranial base.

Adolescent

Malignant skull base tumors.

A multidisciplinary approach to the treatment of malignant cranial base tumors has resulted in improved resections with less morbidity and a greater potential for cure. An improved understanding of the complex anatomy has allowed the development of new surgical approaches and improved methods of reconstruction. The authors' experience with the treatment of malignant neoplasms of the cranial base is reviewed, with emphasis on biologic behavior of this diverse group of neoplasms.

Craniotomy

T-cell markers in tumor-infiltrating lymphocytes of head and neck cancer.

Fresh suspensions of tumor-infiltrating lymphocytes (TIL) from 16 patients with squamous cell carcinoma of the head and neck (SCCHN) were examined for T-cell markers including CD4 (helper-inducer), CD8 (cytotoxic-suppressor), natural killer (NK) cell, and activation surface markers using monoclonal antibodies and two-color flow cytometry. Two of 8 (25%) patients with a CD4/CD8 ratio of less than 1 developed cervical lymph node metastases; none had extracapsular spread. Six of 8 (75%) patients with a CD4/CD8 ratio of greater than 1 developed cervical metastases; 5 of 6 (83%) exhibited extracapsular spread. An increased CD4/CD8 ratio was attributable to a decrease in CD8+ cells. A CD4/CD8 ratio of greater than 1 may be a useful prognostic indicator of the development of cervical metastases.

Adult

Dermatofibrosarcoma protuberans.

The consultants agreed that dermatofibrosarcoma protuberans is characterized by its persistent growth and locally aggressive behavior. However, they did not all agree on the mode of treatment. Drs. Schuller and Snyderman favored surgical resection of the involved areas including the right cheek, lower eyelid, and any necessary portions of the nasal ala and upper lip. They encouraged the use of Moh's chemosurgery to detect microscopic disease. They were also in agreement regarding reconstruction, suggesting a cervical-facial or bi-lobed flap for the cheek. A full-thickness skin graft was recommended for the lower eyelid with primary closure planned for the lip defect. They disagreed on the use of postoperative radiation therapy. Dr. Schuller elected not to irradiate; Dr. Snyderman favored 60 to 65 Gy post-operatively. Dr. Quivey expressed concern regarding the morbidity from such a large resection and extensive reconstruction and suggested primary radiation therapy with external beam. All three consultants felt that good follow-up would include thorough head and neck examinations with MRI and/or CT scans if there were any concern about tumor recurrence.

Adult

Prognostic significance of prostaglandin E2 production in fresh tissues of head and neck cancer patients.

BACKGROUND: Immunosuppressive prostaglandins may play a role in the biologic behavior of head and neck cancer. Increased levels of prostaglandin E2 (PGE2) have been measured in squamous cell carcinoma of the head and neck (SCCHN). METHODS: To address this question, tissue levels of PGE2 were measured in tumor tissues, normal mucosa, and lymph nodes of 37 patients undergoing tumor resections. Tissue specimens were placed in culture media, and levels of PGE2 released into the supernatant were measured by radioimmunoassay. RESULTS: Tissue levels of PGE2 were significantly greater in tumor and normal mucosal tissues compared to lymph nodes (p = 0.0003). There was no difference between metastatic and tumor-free lymph nodes. Although tumor tissue levels of PGE2 were not associated with tumor stage, increased levels of PGE2 were associated with increased 2-year disease-free survival (p = 0.02). CONCLUSIONS: Although PGE2 may have adverse effects on local immune function in tumor tissues, improved survival of patients with increased local PGE2 production may be indicative of an enhanced immunologic response to the tumor which has a favorable impact on outcome.

Adult