[Peculiar features of the coagulation, fibrinolytic, and anticoagulation systems of blood in the patients presenting with vascular ENT tumours].

The objective of the present work was to study characteristics of the blood coagulation system in the patients presenting with vascular ENT tumours including the following parameters: a complete blood count, hemorrhage, coagulation, retraction, and blood clot lysis times. The patients with ENT hemangiomas experienced hypocoagulation in the preoperative period in combination with the predominance of the fibrinolytic processes and elevated levels of free heparin. These changes can be interpreted as a protective reaction to prevent intravascular coagulation in the case of the slow blood flow in hemangiomatous cavities. The results of the study indicate that the prophylactic administration of inhibitors of enhanced fibrinolysis in the preoperative period may be dangerous for the patients presenting with hemangiomas because suppression of this adaptive response prior to surgery is likely to promote massive microcoagulation under the influence of tissue thromboplastin.

[Coagulation factors as potential tumour markers in patients with head and neck carcinomas?]. / Gerinnungsfaktoren als Potenzielle Tumormarker bei Patienten mit Kopf-Hals-Karzinomen?

OBJECTIVE: Carcinomas can have influence on the coagulation system by different factors. Locally pathological changes of metabolism, neo-vascularisation, oxygenation and tissue pressure as well as locally and systemically activities of the tumor cells, are part of it. The coagulation situation in patients with head and neck carcinomata is characterized only insufficiently till now. MATERIAL AND METHODS: In a prospective pilot study 20 male patients with squamous-cell carcinomas of the head and neck area were subjected to a detailed coagulation diagnostics pre and post therapeutically and, age and sex corrected, compared with a control group (n=37). RESULTS: For the routine parameters PTT, Quick, TZ and INR no differences between the groups could be recognized. For the tumour patients a statistically significant increase arose for the acute phase proteins like factor I (fibrinogen), factor VIII, factor IX, von- Willebrand antigen and activity before therapy. Increased values were found also for plasmin, factor II, factor V and the thrombin-antithrombin-III-complex (TAT) whereas the values for antithrombin-III were degraded significantly. In the tumour patients the pre-therapeutical increased values for the activation marker TAT brought themselves back to normal after the tumour ablative therapy. CONCLUSIONS: TAT could be suitable as a potential tumour marker but also for relapse tumours. To evidence this, a study of longer duration and with a larger number of patients is necessary.

Prognostic impact of total tumor volume and hemoglobin concentration on the outcome of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

PURPOSE: To identify prognostic clinical and treatment related factors for local control, distant metastasis-free survival, and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy. PATIENTS AND METHODS: From 1992 to 1995, 68 patients with squamous cell cancer of the head and neck (93% stage IV disease) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique. The total tumor volume (TTV) was quantitatively determined based on computed tomography scans in 56 patients. A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing. RESULTS: The survival and locoregional control rates at three years were 35 and 32%. The multivariate analysis revealed a significant association between the TTV and survival (P = 0.0008) and between the pretreatment serum hemoglobin concentration and locoregional control (P = 0.01) and survival (P = 0.05). The locoregional control was significantly associated with the N-stage (P = 0.007) and there was a good correlation between the N-stage and TTV in this study population. CONCLUSION: Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration. In studies comparing the survival of patients with advanced cancer of the head and neck, the use of the TTV as a covariable may improve the statistical power.

[A new marker in oncology. Assay of gangliosides bound to sialic acid]. / Un nouveau marqueur en cancérologie. Le dosage des gangliosides liés à l'acide sialique.

Gangliosides are released from cells proliferating in serum and can be assayed by a LASA method. The authors report the assay method for sialic acid bound exclusively to glycosphingolipids (GASA method). They study the reliability and discuss the preliminary factors concerning this upper respiratory tract squamous cell marker.

[Immune response to Epstein-Barr virus in patients with otorhinolaryngologic neoplasms of various morphology and invasiveness]. / Osobennosti immunnogo otveta k virusu Epshteina-Barr u bolnykh s opukholiami LOR-organov v zavisimosti ot rasprostranennosti i morfologicheskoi formy opukholi.

Both nasopharyngeal and tumors and epithelial cancer of topographically different sites of the mouth, laryngopharynx are shown to be associated in many cases with high immunity to virus Epstein-Barr (VEB) antigens. VEB-associated antibody quantitation in patients with laryngeal, laryngopharyngeal, oral and lingual cancer revealed that the malignant process dissemination and the tumor differentiation are related to immune response to VEB antigens: the more advanced is cancer and the poorer is its differentiation, the more pronounced is the immune response.

Prognostic and predictive value of serum vascular endothelial growth factor (VEGF) in squamous cell carcinoma of the head and neck.

INTRODUCTION: This study aimed to investigate the prognostic and predictive value of serum vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinoma (HNSCC). METHOD: Preoperative and 6-month postoperative serum VEGF levels were measured using a quantitative sandwich enzyme immunoassay technique in 55 consecutive patients with HNSCC and two control groups. The first control group included normal, healthy, age- and sex-matched individuals (n = 20), while the second control group included the patients who had history of HNSCC and were free of disease for at least 5 years (n = 25). RESULTS: The mean baseline serum VEGF concentrations of the 55 patients with HNSCC and the first and the second control groups were 437.86, 42.56, and 48.03 pg/ml, respectively (P < 0.001). After a median follow-up of 75 months, 15 patients of the study group developed recurrent disease and 40 patients remained free of disease. The mean preoperative and 6-month postoperative serum VEGF levels for the 40 patients who did not have recurrent disease were respectively 327.69 and 153.50 pg/ml compared to 731.72 and 692.96 pg/ml for the 15 patients with recurrent disease (P < 0.001). High (≥540 pg/ml) serum VEGF level was associated with poor overall survival (P < 0.001). Moreover, multivariate analysis showed node stage (P < 0.001) and preoperative serum VEGF level (P = 0.020) as significant, independent prognostic factors for overall survival. CONCLUSION: Preoperative or postoperative elevated serum levels of VEGF are highly predictive for disease recurrence and are associated with poor disease-free and overall survival of patients with HNSCC.

SDF-1-CXCR4 axis: cell trafficking in the cancer stem cell niche of head and neck squamous cell carcinoma.

Stromal cell-derived factor-1α (SDF-1α), also known as CXCL12, has variable effects on a plurality of cells. CXCR4 has been identified as its corresponding receptor. The SDF-1-CXCR4 axis is postulated to be a crucial key pathway in the interaction between (cancer) stem cells and their surrounding supportive cells in the cancer stem cell niche. We evaluated the expression of CD44 as a cancer stem cell marker and of CXCR4 in human HNSCC tissue samples. Afterwards, we monitored the concentration of SDF-1 in peripheral blood samples of HNSCC patients and healthy donors. We showed that CD44 and CXCR4 are expressed in human HNSCC tissues. Markedly, CD44 showed a high expression in HNSCC cells bordering cancer stromal cells. CXCR4 was mainly expressed in HNSCC tumor nests, but not in the surrounding stromal cells. No significant difference was noted between the SDF-1 concentration in the peripheral blood of HNSCC patients compared to healthy donors. We showed that CD44, as a stem cell marker in HNSCC, is located mainly at the borderline of HNSCC tumor nests with the surrounding cells. In addition, we demonstrated that CXCR4 as the corresponding receptor to SDF-1 is highly expressed in HNSCC tumor nests, but not in the tumor stroma. We collected evidence that SDF-1-CXCR4 interaction may be a crucial pathway in cell trafficking in the cancer stem cell niche of HNSCC, while SDF-1 was not detected in the peripheral blood of HNSCC patients. The SDF-1-CXCR4 axis may play an important role in the cancer stem cell theory of HNSCC. As SDF-1α also exhibits a multitude of functional effects on HNSCC cells, such as migration and polarization, it may be possible that the SDF-1-CXCR4 axis is also involved in the pathophysiology of the progression, recurrence and metastasis of malignant disease. Understanding these interactions may help to gain further insight into these mechanisms and as such help to discover new strategies of therapy.

Selenium levels during the course of radiotherapy. No influence of irradiation on blood selenium concentration.

PURPOSE: To evaluate the influence of tumor characteristics and irradiation on blood selenium concentrations and their course during radiotherapy. MATERIAL AND METHODS: Selenium Levels were determined at various times during radiotherapy (I: beginning, II: mid, III: end, IV: 6 weeks after) by atomic absorption spectrometry in whole blood. The values were correlated with patient-, tumor- and irradiation-related parameters. RESULTS: A total of 690 samples were analyzed in 224 patients. The mean selenium value was 75.64 microg/l at the beginning of radiotherapy. 170 patients (77%) had reduced selenium Levels < 89 microg/l. Twelve patients (5.4%), mostly with head-and-neck cancer, had critically low values which need to be controlled and monitored. Three patients (1.3%) with breast cancer had critically increased values. Female patients showed higher seLenium concentrations than male patients (p = 0.0404). Patients diagnosed for head-and-neck cancer had significantly lower seLenium values than breast cancer patients (p = 0.016). Previous treatment by surgery and/or chemotherapy was correlated with lower selenium concentrations compared with irradiation as primary treatment (p = 0.039). According to analysis of variance, there was no significant change of the selenium concentration during the course of radiotherapy (p > 0.05). CONCLUSION: A preexisting selenium deficiency could be diagnosed in the broad majority of cancer patients undergoing radiotherapy. In contrast to the widely held opinion, it was not further aggravated by standard radiotherapy protocols.

[Necessity for blood transfusion in head and neck surgery]. / Notwendigkeit der Bluttransfusion bei ausgewählten Operationen im Kopf-Hals-Bereich.

INTRODUCTION: Sometimes, use of blood products is necessary in head and neck surgery, but blood transfusion also entails risks for the patients and causes high costs for the department. Therefore, we examined the surgical procedures in our department and analysed how often transfusion of blood was necessary and which expenses were incurred. METHODS: Of 3989 operations performed in 1989, 187 patients were found to be at an increased risk for blood loss. The costs for blood group analysis (euro 23.16), cross-testing (euro 13.91) and the transfusion itself (euro 70.35) were estimated in each patient. RESULTS: In 1998 more than 60% of the 187 patients had undergone extensive head and neck surgery for advanced squamous cell carcinoma. Only 17 patients (<15%) received nearly 45% of all units of stored blood transfused that year. In patients who had undergone skull base surgery, the probability of receiving blood was 30%. The transfusion-related costs were estimated to be euro 20,000 during the observation period. Potential savings could have been achieved in cross-testing. CONCLUSION: Preparations should be done on an individual basis. Such preparations are sometimes unnecessary even in patients undergoing surgical procedures with a high risk for blood loss.

[Erythropoietin in patients with head and neck carcinomas?]. / Erythropoietin bei Karzinomen im Kopf-/Halsbereich?

BACKGROUND: Various studies have demonstrated the prognostic significance of the pretherapeutic blood hemoglobin concentration for patients with head and neck cancer following surgery or primary definitive or adjuvant radio- or radiochemotherapy. It was the aim of this study to evaluate whether the prognosis of these patients might be improved when correcting decreased pretherapeutic hemoglobin values by administering erythropoietin. METHOD: In a prospective placebo-controlled double-blind study (Cochrane "evidence-based medicine" level Ib) the effect of erythropoietin was analyzed in patients with locally advanced head or neck tumours with low blood hemoglobin values (women: < 12 g/dL; men: < 13 dL) and a Karnofski value of > 60 following primary definite or adjuvant radiotherapy (up to 70 Gy). The time to local tumour progression and survival was evaluated. Kaplan-Maier estimates were applied and, the relative risk of well-known prognostic factors tested for with a Cox Proportional Hazards model. RESULTS: 157 patients of the Freiburg University ENT-clinic were recruited from 1997 to 2001. Study conduct was performed according to the GCP guidelines. A rapid increase of the blood hemoglobin value happened during the first five weeks of treatment under epoetin beta. Placebo patients experienced only minor changes of the hemoglobin value. Following adjuvant radiotherapy local tumour control probability at two years was 68 % +/- 7 % and 72 +/- 7 % for placebo and epoetin beta patients, respectively (p = 0.64). Patients who had undergone primary definite radiation experienced a local control probability of 36 % +/- 11 % in the placebo arm after two years, compared to epoetin beta with 23 % +/- 11 % (p = 0.05). CONCLUSION: Epoetin beta resulted in prompt and stable correction of blood hemoglobin values in anemic patients with advanced head or neck tumours, but tumour control and survival was impaired particularly in patients with a high tumour burden.

[The SCC antigen is not a reliable tumor marker in the ENT area. Value of squamous cell carcinoma antigen in diagnosis and follow-up of squamous epithelial carcinoma in the head-neck area. Results of a retrospective study over 6 years]. / Das SCC-Antigen ist kein verlässlicher Tumormarker im HNO-Bereich. Stellenwert des Squamous Cell Carcinoma Antigen bei Diagnose und Verlaufskontrolle von Plattenepithelkarzinomen im Kopf-Hals-Bereich. Ergebnisse einer retrospektiven Studie über einen Zeitraum von 6 jahren.

BACKGROUND: In the early 1970s, progress in chemical analysis allowed the assessment of low concentration substances in blood and other body fluids. These techniques led to development of hitherto unknown diagnostic facilities which were tested with respect to malignant tumors. In those days SCC-A was considered a promising substance for aiding in diagnosis and observation in patients with SCC. METHODS: This retrospective study investigates the correlation between tumor size and tumor progress and the SCC-A level in a group of 322 patients (male: n = 291, age 24-87 yrs, mean 56 yrs: female: n = 31, age 38-82 yrs, mean 70 yrs). RESULTS: The diagnostic value of SCC-A turned out to be poor. In 78%, SCC-A levels were low and neither correlated with tumor size nor the presence of metastases. In follow-up the situation was even worse: A reliable correlation between SCC-A and the course of disease was found in 5.8% of patients only. CONCLUSION: The SCC-A could neither reliably contribute to diagnosis nor to follow-up of patients with squamous cell carcinomas of the head and neck.

[Serum concentrations of soluble adhesion molecules sICAM-1 and sVCAM-1 in patients with malignant ENT tumors]. / Serumkonzentrationen der löslichen Adhäsionsmoleküle sICAM-1 und sVCAM-1 bei Patienten mit malignen HNO-Tumoren.

BACKGROUND: Adhesion molecules are implicated in various stages of tumor progression and metastasis. Soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were recently described. The aim of this study was to determine a differences in concentration of these molecules in patients with head and neck squamous cell carcinoma (HNSCC) compared to healthy controls. PATIENTS AND METHODS: We investigated the circulating levels of sICAM-1 and sVCAM-1 in sera from patients with various head and neck squamous cell carcinomas (n = 52) as well as from normal, healthy controls (n = 35). Serum concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Student's t-test was performed. RESULTS: The majority of the patients with HNSCC were found to have high concentrations of sICAM-1 and sVCAM-1. The mean level of sICAM-1 in patients was 313 ng/ml and in the control group 237 ng/ml (p = 0.0005). The mean level of sVCAM-1 in patients was 624 ng/ml and in the control group 435 ng/ml (p = 0.009). The concentrations of sICAM-1 and sVCAM-1 were significantly higher in HNSCC patients. CONCLUSIONS: These results show the difference in expression of these adhesion molecules in patients with HNSCC compared to healthy controls. Endothelial adhesion molecule determination may find clinical applications in the follow-up of cancer therapy. For this reason, studies incorporating the longitudinal follow-up of patients are required.

[Detection of serum concentration of carbohydrate-deficient transferrin (CDT) in patients with head-neck carcinomas]. / Nachweis der Serumkonzentration von Carbohydrate-Deficient-Transferrin (CDT) bei Patienten mit Kopf-Hals-Karzinomen.

It is now well known that chronic alcohol abuse is an important factor for developing head and neck squamous cell carcinoma (HNSCC). While hospitalized, these patients are at great risk for developing an unexpected alcohol-withdrawal syndrome. Compared to common markers of alcohol abuse, carbohydrate-deficient transferrin (CDT) has been found to be more sensitive and specific. It is therefore very useful for detecting alcoholism and controlling compliance of alcohol withdrawal. We analyzed the serum concentrations of CDT, liver enzymes and mean corpuscular volume in 49 male patients with HNSCC. Elevated CDT levels were found in more than 25% of patients who earlier denied a history of chronic alcohol abuse. Over one-third of these patients developed an alcohol-withdrawal syndrome. These findings demonstrated that analysis of elevated CDT serum levels was a valuable method for detecting chronic alcohol abuse and recognizing patients at risk for developing an alcohol-withdrawal syndrome post-operatively.

[Status of essential trace elements in untreated carcinomas of the head and neck]. / Status essenzieller Spurenelemente bei unbehandelten Kopf-Hals-Karzinomen.

BACKGROUND: The changed mineral status is well known in different tumor types. This phenomenon has influenced the redox potential of patients suffering from solid cancers. A prospective trial was conducted to evaluate the specifics for untreated head and neck cancer patients. MATERIAL AND METHODS: We included 100 patients with advanced squamous cell carcinoma of the head and neck region before each kind of treatment. Following serum-concentrations were measured by atom absorption spectrometry: selenium, copper, zinc, and ferrum. Additionally we evaluated the activity of glutathion peroxidase and the concentration of malondialdehyde of the serum. RESULTS: 66 % of all patients have shown a decreased serum-concentration of selenium. These patients were additionally characterized by decreased activities of endogenous glutathionperoxiase. A third of all patients had decreased zinc and iron levels. Copper was found enhanced in 30 %. In trend the malondialdehyde was increasing due to decreasing selenium levels. CONCLUSIONS: Head neck cancer patients show the same characteristic trace element status as other solid tumors: decreased selenium, zinc and iron, increased copper. The therapeutic consequences of these observations are still unclear.

Beta-carbolines in chronic alcoholics undergoing elective tumor resection.

The prevalence of chronic alcoholism in patients with carcinomas of the upper digestive tract exceeds 60%. The patient's history and laboratory markers, preoperatively, are often not sensitive or specific enough to detect alcohol-dependent patients, preoperatively, who are at risk of developing alcohol withdrawal syndrome (AWS) during their postoperative intensive care unit (ICU) stay. Previously, it was found that plasma norharman was elevated in chronic alcoholics, suggesting marker characteristics for chronic ethanol misuse and possibly alcohol dependence. We investigated whether beta-carbolines (i.e., harman and norharman) were different between chronic alcoholics and nonalcoholics with carcinoma, and how the levels change in alcohol-dependent patients during their hospital stay. Ninety-seven patients with oral, pharyngeal, laryngeal, or esophageal carcinomas were evaluated regarding their drinking habits. Sixty patients were transferred to the ICU following tumor resection. Chronic alcoholics met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in chronic alcoholics was > or = 60 g. Blood samples were collected on admission to the hospital, preoperatively, on admission to the ICU and on days 2, 4, and 7 in the ICU. Harman and norharman were determined by HPLC. Elevated norharman was found in chronic alcoholics on admission to the hospital, whereas harman did not differ between groups. On admission, the area under the receiver operating characteristics curve was significantly larger for carbohydrate-deficient transferrin and preoperatively for norharman. The preoperative norharman levels were significantly correlated with the period of mechanical ventilation and the length of ICU stay. Postoperatively, norharman decreased in all patients, except a group of 11 alcohol-dependent patients who developed AWS during their ICU stay. The finding that elevated norharman levels were found in chronic alcoholics on admission to the hospital and preoperatively supports the view of a specific marker for alcoholism. Preoperative norharman was superior to carbohydrate-deficient transferrin and was associated with a prolonged ICU stay and a prolonged period of mechanical ventilation. Further studies are required to determine whether norharman aids in the preoperative diagnosis of chronic alcohol misuse with respect to the prevention of postoperative complications.

[Performances of two kits for parathyroid hormone-related peptide (PTHrP) assay in the additional study of malignant hypercalcemias]. / Performances de deux trousses de dosage du peptide apparenté à l'hormone parathyroïdienne (PTHrP) dans le complément d'exploration des hypercalcémies malignes.

Measurement of parathyroid hormone-related peptide (PTHrP) associated with that of parathyroid hormone, allows to establish, in most cases, diagnosis of hypercalcemia of malignancy and more exactly of patients with Malignancy Humoral Hypercalcemia (MHH). Because of the variety of molecular forms of PTHrP, linked to its catabolism, its immunoassay remains difficult. After a study evaluating the methodological reliability, we measured the contribution of PTHrP to the hypercalcemia by 2 assays: a N-terminal RIA and a 1-72 IRMA in samples from 47 control subjects, 10 patients with chronic renal failure (IRC), 13 patients with primary hyperparathyroidism (HPT), and 48 patients with solid tumors classified by their level of calcemia: 48 normocalcemia and 23 hypercalcemia. We noted a strong correlation (r = 0.92) between the two assays. They do not show increases in renal insufficiency; they have a good diagnostic discrimination between HPT, normal subjects and patients with MHH. Elevated levels of PTHrP are similar in both assays. However, IRMA appears to be more sensitive and more practical than RIA. Moreover, it shows the best correlation between serum calcium and phosphorus in patients with MHH.