Population demographics of American eels Anguilla rostrata in two Arkansas, U.S.A., catchments that drain into the Gulf of Mexico.

The goal of this study was to compare American eel Anguilla rostrata life history in two inland river systems in Arkansas, U.S.A., that ultimately discharge into the Gulf of Mexico via the Mississippi River and the Red-Atchafalaya catchments. From 21 June 2011 to 24 April 2014, 238 yellow-phase A. rostrata were captured in the middle Ouachita River and tributaries using boat electrofishing and 39 in the lower White River using multiple sampling gears. Most of them were caught downstream of dams in both basins (61%). Medium-sized A. rostrata ranging from 225 to 350 mm total length (LT ) were the most abundant size group in the Ouachita River basin, but they were absent from the White River. Mean LT at age 4 years (i.e. youngest shared age) was 150 mm greater for the White River than the Ouachita River basin. Anguilla rostrata appeared to have a greater initial LT (i.e. minimum size upon arrival) in the White River that allowed them to reach a gonado-somatic index (IG ) of 1·5 up to 4 years earlier, and downstream migration appeared to occur 5 years earlier at 100 mm greater LT ; these differences may be related to increased river fragmentation by dams in the Ouachita River basin. Growth and maturation of A. rostrata in this study were more similar to southern populations along the Atlantic coast than other inland populations. Adult swimbladder nematodes Anguillicoloides crassus were not present in any of the 214 swimbladders inspected. Gulf of Mexico catchments may be valuable production areas for A. rostrata and data from these systems should be considered as range-wide protection and management plans are being developed.

Effects of pool isolation on trophic ecology of fishes in a highland stream.

The objective of this study was to examine the effects of pool isolation on fish diet and to answer three questions: Were food resources different or reduced in isolated compared with connected pools? Were fishes more selective and did they increase resource partitioning in isolated pools? Would individuals exhibit increased gastrointestinal tract (GIT) length in isolation to aid nutrient absorption? Benthic macroinvertebrate density and richness were significantly lower in isolated pools compared with connected pools; fishes became more selective and partitioned resources more in isolated pools and all three species showed an increase in GIT length in isolated pools compared with connected pools. With a changing climate predicted to increase intermittency within headwater streams, the results show that these fishes have the adaptive ability to respond and continue to survive.

Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393.

PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) + cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended.

Reliability in evaluating letters of recommendation.

To measure the interobserver reliability in evaluating letters of recommendation for residency applicants, three letters were collected from each of the application files of 58 residents at one program. The letters were rated by six faculty. Interobserver reliability, calculated using the kappa statistic, was slight. These preliminary results show significant variability in the interpretation of letters of recommendation.

Expression of inducible nitric oxide synthase (iNOS) in middle ear epithelial cells by IL-1beta and TNF-alpha.

OBJECTIVE: The importance of nitric oxide (NO) in the development of mucoid middle ear effusion (MMEE) has been reported, but the mechanism regulating NO release is unclear. We hypothesized that middle ear epithelial cells (MEEC) are an important source of NO and that cytokines may be responsible for inducible nitric oxide synthase (iNOS) mRNA expression in middle ear epithelial cells. This study aims to identify and localize iNOS in middle ear epithelium, and to characterize the effects of cytokines IL-1beta and TNF-alpha on the expression and regulation of iNOS in rat middle ear epithelial cells. METHODS: In vitro study: 40 Healthy adult Sprague-Dawley rats weighing 200-250 g were used as donors of MEEC. Cultured MEEC were exposed to IL-1beta (10 ng/ml), TNF-alpha (5 ng/ml) or PBS (negative control) stimulation for 16 h. In vivo study: A total of 45 healthy adult Sprague-Dawley rats weighing 200-250 grams were used for this study. The tympanic bullae were exposed bilaterally by a submandibular approach. Animals were equally divided into three groups and inoculated with either 250 ng of IL-1beta, 250 ng of TNF-alpha or PBS. A PBS group served as control. Expression of iNOS mRNA in MEEC from both in vivo and in vitro studies was determined by RT-PCR using specific primers. Expression of iNOS protein in MEEC was determined by immunocytochemistry and Western blot using specific anti-iNOS antibody. RESULTS: Primary culture of rat MEEC was positively stained by cytokeratin antibody, but not by vimentin, indicating the epithelial origin of the cultured cells. RT-PCR revealed that cultured MEEC without treatment of IL-1 beta or TNF-alpha did not express iNOS mRNA whereas cultured MEEC treated with IL-1beta or TNF-alpha for 16 h expressed iNOS mRNA. Both immunocytochemistry and Western blot demonstrated the expression of iNOS protein in the majority of cultured MEEC treated with IL-1beta or TNF-alpha for 16 h, whereas the expression of iNOS protein was not detectable in MEEC without treatment. Expression of iNOS protein in vivo was observed in middle ear mucosa treated with IL-1beta and TNF-alpha by immunohistochemistry. CONCLUSION: Expression of iNOS mRNA and iNOS protein is induced in MEEC following the treatment of cytokines IL-1beta or TNF-alpha both in vivo and in vitro. The results of the present study demonstrate that rat MEEC possess the capacity to express iNOS after IL-1beta and TNF-alpha stimulation.

Induction of mucin gene expression in middle ear of rats by tumor necrosis factor-alpha: potential cause for mucoid otitis media.

Mucoid otitis media (MOM) is characterized by viscous fluid, high in mucin concentration, which accumulates in the middle ear cavity. Recent studies suggest that initial infection in the middle ear cleft may be key to the development of MOM. However, factors of the initial infection attributed to the stimulation of mucin production are not clearly understood. This study demonstrated that tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine in mucoid effusion, markedly increased Muc2 mucin mRNA expression in middle ear epithelium, in a time- and dose-dependent manner. Parallel to this was a marked increase in mucin glycoprotein in middle ear fluid. Also, TNF-alpha demonstrated an autocrine and/or paracrine effect on the expression of endogenous TNF-alpha gene in the middle ear, which may contribute to the production of mucin in this study. These findings suggest that TNF-alpha plays an important role in the development of MOM by stimulating mucin metabolism.

Metastases to temporal bones from primary nonsystemic malignant neoplasms.

OBJECTIVES: To compare histopathological and clinical findings of metastasis to the temporal bone with previous reports and to determine the prevalence of these metastases in patients with nonsystemic cancer. STUDY DESIGN: Retrospective. METHODS: Autopsy records of 864 patients were screened to select those with primary nondisseminated malignant neoplasms. These were evaluated histopathologically for metastasis to and site of involvement within the temporal bone, and histological characteristics of the tumor. Clinical records and autopsy reports were reviewed for demographic data, clinical course, otologic and vestibular manifestations, site of primary and its histological features, extent of metastasis, and mode of spread. RESULTS: Of 212 patients with primary nondisseminated malignant neoplasms, 47 had metastases to the temporal bone (76 temporal bones). Twenty different primary tumors had metastasized, most commonly breast cancer. Hearing loss was the most common otologic symptom (seen in 19 patients [40%]), while 17 (36%) had no otologic or vestibular symptoms. Temporal bone involvement was bilateral in 29 patients (62%). Most metastases to the temporal bone demonstrated hematogenous spread in 58 temporal bones (76.7%), and petrous apex was the most common site of metastases in 63 temporal bones (82.9%). Temporal bone metastases were not observed in cases where the primary tumor was adequately treated. CONCLUSIONS: In the largest series to date, we found temporal bone metastases more frequently than previously reported. Absence of temporal bone involvement in cases in which the primary tumor was adequately treated stresses the need for early management of cancer. Metastatic disease must be considered as a cause of hearing loss in patients with a history of malignant neoplasm.

Subcellular immunolocalization of protein kinase CK2 in normal and carcinoma cells.

CK2 is a messenger-independent protein serine/threonine kinase that has been implicated in cell growth and proliferation. Our recent analysis of squamous cell carcinomas of the head and neck (SCCHN) revealed a significant elevation in CK2 activity in these tumor cells relative to normal mucosa of the upper aerodigestive tract and suggested a correlation with aggressive tumor behavior and poor clinical outcome. In order to further define the distribution of CK2 in these tissues, we have examined the immunohistochemical staining pattern of surgical specimens of both SCCHN tumors and normal upper aerodigestive tract mucosa using a monoclonal antibody directed against the catalytic subunit CK2-alpha of the kinase, and have compared these data with the subcellular distribution of CK2 activity in these same tissues. These measurements showed that CK2 is predominantly localized to the nuclei of the tumor cells, which agreed closely with the immunohistochemical staining pattern of CK2-alpha in tumor cells. The chiefly nuclear distribution of CK2-alpha immunostaining found consistently in SCCHN tumor cells and tumor-infiltrating lymphocytes contrasted with a relatively more predominant cytosolic staining pattern exhibited by various cellular constituents of normal oropharyngeal mucosa. The immunostaining pattern of CK2-alpha revealed that staining was observed in the cells stained for the proliferation-marker Ki-67; however, strong distinct immunostaining for CK2-alpha was also observed in large numbers of other cells in these same tumors, suggesting that CK2 elevation in these tumors is not a reflection of proliferative activity alone, but may also relate to the pathobiological behavior of the tumor.

Preoperative permanent balloon occlusion of internal carotid artery in patients with advanced head and neck squamous cell carcinoma.

OBJECTIVE/HYPOTHESIS: To determine the value of preoperative balloon occlusion in predicting the safety of carotid artery resection in advanced recurrent head and neck squamous cell carcinoma. STUDY DESIGN: Retrospective chart review of all cases undergoing planned carotid artery resection for recurrent disease at a major university hospital. METHODS: If the carotid artery was encased, a nonemergent carotid artery balloon test occlusion was performed for 30 minutes. If the patient tolerated this, he or she underwent permanent carotid artery occlusion. RESULTS: Twenty-three patients were prospectively evaluated for resection. Three underwent emergent carotid artery ligation. Twenty others underwent nonemergent carotid artery test occlusion. Of these, 5 patients failed preoperative carotid artery balloon occlusion and 15 patients successfully underwent permanent carotid balloon occlusion. Although eight of these patients died of recurrent disease in less than 1 year, seven patients survived more than 1 year with two patients surviving more than 2 years. CONCLUSIONS: Preoperative carotid balloon occlusion predicted patients who could tolerate permanent occlusion. All patients eventually developed recurrent disease, but in 14 of the 15 patients, no hemorrhages occurred.

Basaloid squamous carcinoma: a clinical comparison of two histologic types with poorly differentiated squamous cell carcinoma.

Basaloid squamous carcinoma (BSC) of the head and neck has been shown to have a poor prognosis when compared with conventional squamous cell carcinoma (SCC). Pathologically, specimens determined to be BSC can have nearly pure basaloid features (group 1) or a mixture of basaloid and squamous features (group 2). The clinical behavior in these 2 subgroups has not been compared previously. BSC is also commonly confused histologically with poorly differentiated SCC (PDSCC). A retrospective comparison of disease stage at presentation, rate of distant metastasis, rate of local recurrence in those offered surgical resection, and rate of survival is made to compare outcomes of the 2 BSC groups and the PDSCC group. The presence of particular histologic features may be associated with poorer outcomes. Patients with BSC have advanced disease at presentation. Survival in the BSC group was less than half that in the PDSCC groups. Statistical analysis shows the 2 groups to be well matched with regard to stage and site of disease. Presence of neck nodal disease on presentation predicts poor survival. In this study distant metastases occurred in 52% of patients with BSC and in 13% of patients in the PDSCC group. The local recurrence rate is comparable for BSC and conventional SCC, with even early tumors in the BSC group recurring distantly rather than locally or regionally. Considering the high distant metastatic rate of BSC and poorer overall survival rate, a more extensive metastatic survey is indicated in these patients before surgery is recommended. We recommend that patients with a diagnosis of BSC not be included with conventional SCC groups in prospective randomized cancer protocols.

Early-response cytokine expression in adult middle ear effusions.

Various cytokines are presently known to be associated with the regulation of inflammatory responses. In pediatric otitis media, cytokines that correlate with various degrees of inflammation are present in middle ear effusions as inflammatory mediators. The present study was undertaken to examine the potential role of the early-response cytokines, interleukin-1beta and tumor necrosis factor-alpha, in adult otitis media. Fifty-nine adults with otitis media underwent tympanocentesis, and the effusion specimens were analyzed for the presence of both cytokines by enzyme-linked immunosorbent assay methods. Eighty-eight percent of the effusions were serous in nature. Sixty-seven percent of the patients had a known history of head and neck malignancy and radiation to the temporal bone. Twelve percent of the effusions were positive for interleukin-1beta expression, compared with 85% of effusions in children with otitis media. Eight percent of the effusions contained tumor necrosis factor-alpha, compared with 85% of those collected in pediatric otitis media. All of the specimens that contained tumor necrosis factor-alpha also contained interleukin-1beta. In the present study, there was no correlation with head and neck malignancy/radiation or the clinical degree of inflammation with the presence of either cytokine. We conclude that adult otitis media is associated with lower expression of an acute inflammatory response, as judged by the levels of interleukin-1beta and tumor necrosis factor-alpha in the effusions. Additionally, adult otitis probably represents a less severe and more chronic inflammatory state in comparison with pediatric otitis media. Further analysis of inflammatory mediators in adult otitis media is necessary to evaluate the contribution of cytokines in relation to various etiologic factors.

Histopathology of human temporal bone after cis-platinum, radiation, or both.

Preserving organs by use of multiple modalities has become protocol in treating squamous cell carcinomas of the head and neck, but cis-platinum and radiation can impair hearing. To determine the effect of cis-platinum, radiation, or a combination of these treatments on the temporal bone, we studied histopathologic slides of 15 human temporal bones: four after cis-platinum, five after radiation, two after combined treatment, and four from normal controls. Hair cells and cells in spiral ganglia were counted in reconstructed organs of Corti. Lumen-to-diameter indexes in arterioles near facial nerves were quantified for four normal controls and seven irradiated patients. Available audiograms were compared. Decreased spiral ganglion cells, loss of inner and outer hair cells, and atrophy of stria vascularis were demonstrated in groups receiving cis-platinum, radiation, and combinations, compared with age-matched controls. Arterioles around facial nerves demonstrated fibrinous clots within the intima, endothelial proliferation, and hypertrophy and fibrosis of vascular walls in smooth muscle. Fibrosis in connective tissue was clearly progressive after radiation. Cis-platinum and radiation can contribute to otologic sequelae, including sensorineural hearing losses, vascular changes, serous effusion, or fibrosis. Prophylactic treatments and techniques to deliver them should be considered for protection of temporal bones and preservation of hearing after oncologic modalities.

Long-term survival in rhinocerebral mucormycosis. Case report.

Mucormycosis refers to a group of rapidly progressive infections caused by fungi belonging to the order Mucorales. Infection most often develops in individuals with immunological or metabolic compromise, although patients without underlying abnormalities have been affected. Specific clinical manifestations are associated with various predisposing factors. Rhinocerebral mucormycosis is the most common form and most frequently develops in individuals with poorly controlled diabetes mellitus. The extent of anatomical involvement and clinical course are unpredictable, depending on the intrinsic factors of the host. Over the past 20 years the prognosis for patients with rhinocerebral mucormycosis, once considered to be a uniformly fatal disease, has improved. Coordinated medical and surgical treatment, including rapid diagnosis, the advent of systemic antifungal agents, aggressive surgical debridement, and control of the underlying disease process, have been credited with its successful management. The range of survival rates recorded with the regimen of combined therapies is wide because the number of patients reported is limited and anatomical involvement is diverse. Survival with intracerebral abscess is rare. The authors describe the successful management of a patient who developed a bifrontal fungal abscess during treatment for rhinocerebral mucormycosis associated with ketoacidosis and diabetes mellitus. The patient remains without radiographic or clinical evidence of infection more than 2 years after treatment. The authors review the characteristic clinical, radiographic, and pathological features of previously reported infections and emphasize the importance of early detection and aggressive treatment in the management of this frequently fulminant and fatal disease.

A critical assessment of factors influencing reliability in the classification of fractures, using fractures of the tibial plafond as a model.

OBJECTIVE: To investigate three factors that may influence the reliability of a fracture classification system: (a) the quality of the radiographs; (b) the ability of observers to identify the fracture fragments; and (c) the use of binary decision making. DESIGN: Assessment of interobserver reliability of blinded observers. SETTING: Medical school department of orthopaedics. PARTICIPANTS: Two attending orthopaedists, two PGY-5 orthopaedic residents, and two PGY-3 orthopaedic residents served as observers. INTERVENTION: Observers classified radiographs of twenty-five tibial plafond fractures according to the Rüedi-Allgöwer and binary classification systems, and also rated the quality of each radiograph as adequate or inadequate for accurately classifying the fracture. At a second session, observers classified the same radiographs after marking the fragments of the tibial articular surface, as well as radiographs that had the articular fragments premarked by the senior author. MAIN OUTCOME MEASURES: Pairwise interobserver reliability was analyzed by kappa statistics, and mean kappa values were compared for each method of fracture classification. RESULTS: No difference in interobserver reliability was detected between the Rüedi-Allgöwer and binary classification systems. Interobserver agreement on the adequacy of the radiographs was poorer than agreement on the classification of the fractures themselves. Having observers mark the fragments of the tibial articular surface had no effect on interobserver reliability; having the articular fragments premarked, however, significantly improved interobserver reliability in classifying the fractures. CONCLUSIONS: The results of this study underscore the complexity of tibial plafond fractures and the difficulty observers have in reliably interpreting fracture radiographs. Fracture classification systems, such as the Rüedi-Allgöwer, predicated on identification of the number and displacement of articular fragments, may inherently perform poorly on reliability analyses because of observer difficulty in reliably identifying the fragments. Because binary decision making did not improve the reliability of fracture classification in this study, further investigation of the effectiveness of binary decision making may be advisable before such strategies are put into widespread use.

Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients.

Invasive fungal sinusitis can develop in immunosuppressed patients. A more complex problem is immunosuppressed patients who have undergone bone marrow transplantation. For a prolonged period, they are both neutropenic and thrombocytopenic. Survival in these patients is poor, and the role for extensive surgical intervention for sinus disease has to be weighed against the risk and the potential that this is a systemic disease. Between January 1983 and June 1993, 29 bone marrow transplant recipients with documented invasive fungal infections of the sinuses and paranasal tissues required surgical intervention. This represents 1.7% of the total 1692 bone marrow transplants performed. There were 22 allogeneic, 6 autologous, and 3 unrelated donor transplants, with two patients receiving two separate grafts. Underlying diseases included 24 hematologic malignancies and 5 other disorders, including 1 aplastic anemia and 1 solid tumor. The mortality rate from the initial fungal infection was 62%. Twenty-seven percent resolved the initial infections but subsequently died of other causes. All patients received medical management, such as amphotericin, rifampin, and colony-stimulating factors, in addition to surgical intervention. Surgical management ranged from minimally invasive procedures to extensive resections including medial maxillectomies. Sixty-one percent of the patients who died of the initial infection had undergone extensive surgical procedures versus 55% of those who resolved the infection. Recovery of neutrophil counts was required to clear the infection but did not necessarily predict a good outcome because 50% of those who died of the infection had experienced neutrophil recovery. White blood cell counts at the time of surgery were not significantly different between the two groups. Prognosis was poor when cranial and orbital involvement and/or bony erosion occurred.

Dexamethasone inhibits mucous glycoprotein secretion via a phospholipase A2-dependent mechanism in cultured chinchilla middle ear epithelial cells.

Inhibition or attenuation of mucous hypersecretion in middle ear epithelium is a key step toward resolution of mucoid otitis media. Mucous hypersecretion induced by platelet-activating factor (PAF) in cultured Chinchilla middle ear epithelial cells is dependent on arachidonic acid metabolites via PAF receptors, suggestive of the role of phospholipase A2 (PLA2) in mucous glycoprotein (MGP) secretion. In this study, dexamethasone added to cultured Chinchilla middle ear epithelial cells inhibited baseline and PAF-induced MGP secretion in a concentration-dependent manner. A definite time lag (16 h) was observed between administration of dexamethasone and MGP inhibition. This inhibition was reversed by the addition of exogenous PLA2 (the rate-limiting enzyme of arachidonic acid metabolism) and actinomycin D (an inhibitor of mRNA synthesis). This suggests that dexamethasone inhibits baseline and PAF-induced MGP secretion via a PLA2-dependent mechanism.

Nuclear matrix proteins as malignant markers in squamous cell carcinoma of the head and neck.

OBJECTIVE: To test the hypothesis that transformation of normal upper aerodigestive mucosa to squamous cell carcinoma of the head and neck (SCCHN) is associated with specific changes in nuclear matrix (NM) proteins. DESIGN: Retrospective, nonrandomized investigation using a cellular fractionation sequence followed by 2-dimensional gel electrophoresis analysis of NM proteins. SUBJECTS: Nuclear matrix proteins were extracted from a cohort of 12 pathologic SCCHN specimens and 5 normal specimens of oropharyngeal mucosa. RESULTS: All SCCHN specimens examined expressed 11 NM proteins that were not detected in normal mucosa. Conversely, at least 4 NM proteins that were expressed by all specimens of normal mucosa were absent from all SCCHN tumors. Seven NM proteins were common to carcinomas and normal specimens. Spindle cell histological variants of squamous cell carcinoma had distinct NM patterns. CONCLUSIONS: Malignant transformation of normal upper aerodigestive mucosa to SCCHN is associated with specific changes in NM composition. These data suggest that different NM proteins might serve as specific tumor markers.

An ECOG phase II study of amonafide in unresectable or recurrent carcinoma of the head and neck (PB390). Eastern Cooperative Oncology Group.

The purpose of this study was to determine the efficacy and toxicity of amonafide in unresectable or recurrent head and neck cancer and to determine if the degree of toxicity with amonafide correlated with the acetylator phenotype of the patient. Thirty patients were registered on the study and received amonafide, 300 mg/m2, over two hours each day for five consecutive days every 21 days. There was one partial response (3%) which lasted four months. The dose-limiting toxicity was myelosuppression. Acetylator phenotype was determined prior to treatment using HPLC to quantitate caffeine metabolites in urine samples after administration of caffeine. This pharmacokinetic evaluation was performed in 21 patients and revealed that (17/21) 81% of the patients were slow acetylators and 19% of the patients were rapid acetylators. No association was found between acetylator phenotype and toxicity in our patient population. Based on this study, it appears that amonafide given at 300 mg/m2 for 5 consecutive days every 21 days is not active in squamous cell carcinoma of the head and neck, and that acetylator status does not correlate with toxicity.

Tumor infiltrating lymphocytes in squamous cell carcinoma of the head and neck: mechanisms of enhancement using prostaglandin synthetase inhibitors.

Indomethacin has been shown clinically to inhibit growth of SCCHN (Panje, 1981). This inhibition appears to be due to augmentation of cellular immunity. The inhibitory effect of indomethacin may act by limiting tumor associated prostaglandin E2 production, thereby allowing return of costimulatory cytokines by antigen presenting cells. This would have the net result of relief from host unresponsiveness and promotion of B-cell and CTL differentiation, allowing the individual to mount an effective response. The enhancement of tumor infiltrating lymphocytes in SCCHN seen with indomethacin administration could presumably be further augmented when given in combination with cytokine therapy. Future investigation may allow the biochemical staging of an individuals' tumor to determine the optimal combination of cytokine therapy and prostaglandin inhibition through selective use of NSAID's. The effect of NSAID manipulation of prostaglandin and leukotriene metabolism on prevention of metastatic disease in SCCHN has yet to be studied. Given that a preselected, potentially responsive subset of immunocytes exists within the tumor tissue and lymph nodes, the development of the LAK phenomenon in TIL's and tumor draining lymph nodes from surgical specimens is a viable and exceedingly interesting area for future investigations in autologous LAK immunotherapy. The potential exists to harvest a preselected population of tumor infiltrating (Boscia, 1988) or tumor draining immunocytes (McKinnon, 1990). These can then potentially be returned to a state of antigen responsiveness with a combination of cytokine exposure (e.g. rIL-2) and systemic cytokine therapy. With subsequent inhibition of tumor associated prostaglandin synthesis by the systemic administration of prostaglandin synthesis inhibitors, it may be possible to successfully alter the host response to tumor.