Occult metastasis is no burden factor in oral squamous cell carcinoma patients when adhering to a standardized approach in neck dissection.

OBJECTIVES: Management of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival. MATERIAL AND METHODS: A retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach. RESULTS: Four hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor. CONCLUSIONS: Overall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients. CLINICAL RELEVANCE: None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes.

Competitive inhibition of human brain hexokinase by metrizamide and related compounds.

We have compared the competitive inhibitory effects of 2-deoxyglucose, glucosamine, N-acetylglucosamine, N-benzoylglucosamine, and the commonly used radiographic and density gradient agent metrizamide (2-[3-acetamido-2,4,6-triiodo-5-(N-methylacetamido) benzamido]-2-deoxyglucose) on the mitochondrial and soluble forms of human brain hexokinase. Metrizamide produces a classical competitive inhibition with glucose for human brain hexokinase, with Kis of 2.8 and 2.5 mM, respectively, for the mitochondrial and soluble forms. Glucosamine exhibited Kis of 0.58 and 0.29 mM, while 2-deoxyglucose exhibited Kis of 0.074 and 0.15 mM and N-acetylglucosamine 0.098 and 0.092 mM for these two forms, respectively. N-Benzoylglucosamine was by far the most effective inhibitor tested, with Ki values of 0.0086 and 0.022 mM, respectively. In order of increasing potency as a competitive inhibitor for mitochondrial hexokinase are metrizamide, glucosamine, N-acetylglucosamine, 2-deoxyglucose, and N-benzoylglucosamine. For the soluble form of the enzyme in increasing potency are metrizamide, glucosamine, 2-deoxyglucose, N-acetylglucosamine, and N-benzoylglucosamine. Since N-benzoylglucosamine was over 100 times more potent than metrizamide, some of the effects of metrizamide could be due to contamination by N-benzoylglucosamine. However, gas chromatography-mass spectrometry analysis of metrizamide did not indicate the presence of N-benzoyl-glucosamine. In addition, column chromatographic separation of commercially available metrizamide and reconstitution of freeze-dried eluate fractions localized the inhibitory effect to the metrizamide peak.

Autoradiographic method for quantitative evaluation of the blood-brain barrier effects of contrast media.

Opening of the blood-brain barrier after intravenous injection of different contrast media has been investigated by a quantitative autoradiographic technique using 14C-aminoisobutyric acid (AIB) as the blood-brain barrier radiotracer. In this study, experiments were carried out in adult rats. Animals were injected intravenously with 2 ml/kg of the tested contrast medium, and immediately afterward with the blood-brain radiotracer AIB. The following contrast media have been tested: diatrizoate 38%, ioxithalamate 38%, ioxaglate 38%, the nonionic product metrizamide 40%, and a new nonionic product P-297, 400 mg l/ml. Control animals were injected intravenously with saline 0.9% (2 ml/kg) before the injection of the tracer. The degree of blood-brain barrier opening was quantitatively assessed by calculating the capillary rate constant for blood-to-brain transfer of AIB (ki) from the brain activity and the arterial integral for a 6 min experiment. Preliminary data seem to indicate that the intravenous injection of 2 ml/kg of a constant medium may produce a tiny opening of the blood-brain barrier. But, if this is so, this blood-brain barrier opening is of a very low magnitude in the normal brain and there are no obvious differences between the test contrast agents injected intravenously.

Release of serotonin from human platelets in vitro by radiographic contrast media.

Both ionic and nonionic, monomeric and dimeric contrast media were found to release serotonin from intact human platelets in vitro. The monomeric contrast media were compared at the concentration range of 25 mg I/ml. Iothalamate was the strongest and the statistically equal metrizamide iopamidol, and P-297 were the weakest releasers. Monomeric and dimeric contrast media were compared at concentration ranges of 50 and 100 mg I/ml. They ranked, in descending order of serotonin releasing potency: iodipamide, iothalamate, P-127, iopamidol, and a statistically indistinguishable group of the monoacid dimer P-286, the nonionic dimer ZK 74 435, and metrizamide. The capability of contrast media to release serotonin seems to be a composite result of their specific physical and molecular structural properties.

Elimination of aqueous myelographic contrast media from the subarachnoid space.

Elimination of aqueous contrast media from the lumbar subarachnoid space was measured. Iodine concentrations in serum and cisterna magna cerebrospinal fluid were studied in animals undergoing myelography with metrizamide, iocarmate, Iopamidol, or P-297. We found that all four contrast media were eliminated rapidly into the serum and urine, and transported slowly into the basal cisterns.

Direct myocardial effects of intracoronary administration of new contrast materials with lost osmolality.

The effects of LV dynamics of the intracoronary administration of three new contrast materials with reduced osmolality were compared with those of a monomeric ionic material, sodium iothalamate, and the nonionic material, metrizamide. In eight anesthetized dogs, the monacid dimer, P286, caused increases in LV dimensions and decreases in LV systolic pressure and parameters of the contractile state. The changes were less than those caused by sodium iothalamte. The alterations in LV function tended to be greater, but not significantly so, during systemic hypoxemia compared to the normal state. The nonionic materials, P297 and iopamidol, like metrizamide, caused no deleterious effects on LV dynamics in either the normal or hypoxemic state. Nonionic materials actually caused a slight increase in parameters of the LV contractile state.

Development and evaluation of a new water-soluble iodinated myelographic contrast medium with markedly reduced convulsive effects.

A new water-soluble myelographic contrast agent with more hydrophilic properties than metrizamide was developed and tested in the primate (Macaca mulatta) and the cat. A new animal model that allows study of the convulsive effects of intrathecally administered contrast agents in the awake monkey was designed. With this sensitive model the new contrast agent was shown to have a remarkable reduced convulsive effect when compared with metrizamide and other media. Intrathecal hypertonic solutions in the cat depress the evoked cortico-spinal responses whereas the neurotoxic effects of the iodinated water-soluble contrast media increase them. The net effect is a combination of the two actions.