Twenty-year experience with salvage total laryngectomy: lessons learned.

OBJECTIVE: The purpose of this study was to evaluate the outcome of salvage total laryngectomy and identify areas for further improvement. METHOD: A retrospective analysis of all patients who underwent salvage total laryngectomy between January 1999 and December 2018 was performed. RESULTS: Thirty-one patients were identified. The most common primary tumour site was the glottis (83.8 per cent). Early stage (T1-T2) disease was identified in 83.9 per cent of cases. Overall survival at 2 and 5 years post-salvage total laryngectomy was 71 per cent and 45 per cent, respectively. Disease-free survival at 2 and 5 years post-salvage total laryngectomy was 65 per cent and 42 per cent, respectively. The rate of post-salvage total laryngectomy pharyngocutaneous fistula was 29 per cent. CONCLUSION: More than half of patients will not survive beyond five years after salvage total laryngectomy. Regional recurrence was the most common form of failure and death. From this study, elective lateral and central neck dissection is advocated in patients with early laryngeal cancer who present with an advanced recurrence.

Benefits of using BODIPY-porphyrin dyads for developing deep-red lighting sources.

The syntheses, as well as the photophysical and electrochemical characterization, of two novel BODIPY-porphyrin dyads and their first application in lighting schemes are provided. The benefits ascribed to their unique features, namely (i) a good electronic alignment, (ii) a remarkable efficient energy transfer, and (iii) excellent film morphology, lead to deep-red lighting devices with stabilities of around 1000 h and efficiencies of 0.13 Lm W(-1).

Effectiveness of current teaching methods in Cardiology: the SKILLS (medical Students Knowledge Integration of Lower Level clinical Skills) study.

INTRODUCTION: The aim of the study is to assess reported changes in medical students' capacity to attain five basic cardiological clinical skills, following a one-month intensive cardiology course provisioned in the core curriculum. MATERIALS AND METHODS: An anonymous questionnaire comprising self reported performance in the five skills, namely 1) arterial blood pressure measurement, 2) cardiac auscultation, 3) electrocardiogram (ECG) carry out, 4) ECG interpretation and 5) defibrillation, was distributed to 177 fifth year students of the Athens Medical School upon initiating the cardiology course (pre-training group) and to 59 students matched for sex, age, year of study and training centre, following completion of the course (post training group). Comparison of pre- and post- training performance was evaluated using the χ(2) test. RESULTS: No change was noted with regards to blood pressure measurement, cardiac auscultation or defibrillation. By contrast, a statistically significant improvement was reported for ECG execution (54.3 versus 81.4%; p<0.001) and interpretation (from 33.1 to 89.8%; p<0.001). CONCLUSIONS: Improvement in the execution and interpretation of ECGs seems to be among the strengths of the cardiology training program. Further studies including larger samples from multiple medical schools and objective assessment of skill execution might facilitate accurate training evaluation and define opportunities for improvement.

Cyclin D1, EGFR, and Akt/mTOR pathway. Potential prognostic markers in localized laryngeal squamous cell carcinoma.

INTRODUCTION: EGFR (epidermal growth factor receptor), cyclin D1 and Akt/mTOR pathways are active in head and neck cancer. The aim of this study was to explore biomarker expression, their correlations with clinicopathological parameters and their prognostic utility in a cohort of patients with localized squamous laryngeal carcinoma. PATIENTS AND METHODS: We assessed relative messenger RNA expression of EGFR, Akt1, 2, and 3, mTOR and CCND1, copy number variants of the EGFR and CCND1 genes and immunohistochemical protein expression of EGFR, p-Akt308, p-Akt473, pmTOR, PTEN, p53 and cyclin D1 in paraffin-embedded tissue samples of localized laryngeal carcinomas. RESULTS: In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumors of the larynx, high EGFR and CCND1 mRNA correlated with no or ex-smoking, (p = 0.003 and p = 0.029, respectively), while low Akt3 mRNA correlated with alcohol abuse, N0 stage, total laryngectomy, and absence of neck dissection. At a median follow-up of 74.5 months, high mTOR mRNA expression was marginally associated with shorter disease-free survival (hazard ratio [HR] = 1.54; p = 0.093) and high Akt3 mRNA with shorter overall survival (HR = 1.49; p = 0.0786), in univariate analysis. In multivariate analysis, node-positive status, subglottic-transglottic location, surgery other than total laryngectomy and mTOR/CCND1 mRNA interaction with a hazard ratio of 2.16 (p value for interaction: 0.0010) were independent predictors of relapse, while node-positive status and subglottic-transglottic location were associated with higher risk for death. CONCLUSION: In localized laryngeal cancer, clinicopathological parameters and an interaction of high mTOR and CCND1 mRNA expression were found to be associated with poor patient outcome.

Laryngeal cancer: epidemiological data from Νorthern Greece and review of the literature.

BACKGROUND: Cancer of the larynx accounts for 1% to 2.5% of all human neoplasms and is the most common malignancy of the Head and Neck region. The purpose of this study is to analyze epidemiological data of patients with laryngeal cancer and to point out the geographical variations. METHODS: This is the first systematic recording of the laryngeal cancer epidemiological data in Northern Greece. During the period 1992-2010 1,638 patients were diagnosed with and treated for malignant head and neck tumors. One thousand one hundred and four cases (67.4%) were malignant laryngeal tumors, 98.4% of which (1,088 cases) were squamous cell carcinomas (SCC). Only 16 patients (1.5%) presented with other types of malignancies. RESULTS: The average age of the SCC patients was 62.1 years. Only 35 patients were women (3.2%). More than 60% of the patients were farmers or labor workers, 86.9%, were smokers, 43.2% were consuming alcohol on a daily basis and 36.1% had a positive family history of malignancy. Concerning tumor location, 60.2% were glottic cancers. T staging revealed that 1.2% of the cases were carcinomas in situ, 28% T1 tumors, 19% T2, 32 % T3, and 20% T4. Tumor grading showed that 43% of the cases were G1, 42.1% were G2, and 11.8% were G3. CONCLUSIONS: The pathogenesis of laryngeal carcinoma is the result of the combined action of endogenous and environmental factors. The recording and analysis of the epidemiology of the disease is important for its better study and understanding.

Prognostic utility of angiogenesis and hypoxia effectors in patients with operable squamous cell cancer of the larynx.

Angiogenesis is active in localised laryngeal squamous cell carcinoma. We assessed relative messenger RNA (mRNA) and immunohistochemical (IHC) expression of Vascular Endothelial Growth Factors (VEGF) A, B, C, their receptors VEGFR1, 2, 3, Neuropilins 1, 2 (NRP1, 2) and Hypoxia-Inducible Factor 1A (HIF1A) in paraffin-embedded localised laryngeal carcinomas. In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumours of the larynx, high VEGFA and VEGFR1 mRNA correlated with advanced T stage, while low VEGFB and VEGFC mRNA with alcohol abuse and supraglottic primary, respectively (p<0.05). Age <55 was associated with high IHC expression of VEGFA, C and poor tumour differentiation with high IHC VEGFA. At a median follow-up of 74.5months, patients with VEGFR1-high tumours had significantly poorer disease-free survival (Hazard Ratio [HR] 1.93, p=0.008) and shorter overall survival (OS, HR 1.71, p=0.041). An association with dismal OS was seen for high VEGFR3 tumoural mRNA expression (HR 1.76, p=0.02). IHC expression of VEGF family proteins in the tumour was not prognostic and had poor concordance with mRNA expression (kappa<0.1, p=NS). In multivariate analysis, node-positive status, non-supraglottic localization, high VEGFR1 mRNA and high IHC VEGFA expression were significantly associated with relapse, while node-positive status, high VEGFR1 and VEGFC mRNA expression in the tumour with risk of death. In laryngeal cancer, upregulated mRNA expression of VEGFR1 and VEGFC is associated with poor patient outcome.

Identification and validation of gene expression models that predict clinical outcome in patients with early-stage laryngeal cancer.

BACKGROUND: Despite improvement in therapeutic techniques, patients with early-stage laryngeal cancer still recur after treatment. Gene expression prognostic models could suggest which of these patients would be more appropriate for testing adjuvant strategies. MATERIALS AND METHODS: Expression profiling using whole-genome DASL arrays was carried out on 56 formalin-fixed paraffin-embedded tumor samples of patients with early-stage laryngeal cancer. We split the samples into a training and a validation set. Using the supervised principal components survival analysis in the first cohort, we identified gene expression profiles that predict the risk of recurrence. These profiles were then validated in an independent cohort. RESULTS: Gene models comprising different number of genes identified a subgroup of patients who were at high risk of recurrence. Of these, the best prognostic model distinguished between a high- and a low-risk group (log-rank P<0.005). The prognostic value of this model was reproduced in the validation cohort (median disease-free survival: 38 versus 161 months, log-rank P=0.018), hazard ratio=5.19 (95% confidence interval 1.14-23.57, P<0.05). CONCLUSIONS: We have identified gene expression prognostic models that can refine the estimation of a patient's risk of recurrence. These findings, if further validated, should aid in patient stratification for testing adjuvant treatment strategies.

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.

BACKGROUND: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. PATIENTS AND METHODS: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). RESULTS: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. CONCLUSION: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

The role of tumor size and patient's age as prognostic factors in laryngeal cancer.

BACKGROUND AND AIM: The loco-regional recurrence of laryngeal carcinoma in patients who underwent total laryngectomy is related to numerous factors. Aim of the present study was to investigate the role of patient's age and tumor size in the recurrence rate of patients. Additional aim of the current study was to investigate the possible associations between the size of the tumor and other characteristics. PATIENTS AND METHODS: In 1st Department of Otorhinolaryngology of AHEPA University Hospital, from 1992 to 2007, 255 patients with laryngeal carcinoma underwent total laryngectomy. Accurate data regarding the size of the tumor were obtained. Total laryngectomy was the initial treatment in 212 patients, while in the remaining 43 patients was performed as salvage surgery after recurrence. RESULTS: The median tumor size was 2.74 cm (0.8-5.5 cm). There was no significant difference in the median tumor size between the patients who had recurrence (2.87 cm) and the disease free patients (2.69 cm). The median size of glottic tumors (2.47 cm) was smaller than that of supraglottic (2.95 cm) and of subglottic tumors (3.27 cm) (p<0.05). Among the 255 patients, recurrence of the tumor occurred in 73 (28.7%). Statistical analysis of the data showed that the tumor size was affecting the recurrence rate in a different manner, according the stage of the tumor. The recurrence rate in T3 neoplasms was higher in larger tumors than in smaller (13.2% for tumors<2cm, 62% for tumors>4cm), while T4 carcinomas appeared to have the opposite behavior (66.5% for tumors <2cm, 23% for tumors >4cm). The median tumor size in T4 patients that recurred was smaller than in those with no recurrence (2.8 cm Vs 3.3 cm). This behavior was observed in T4 tumors from all sites. Patients who experienced recurrence and had positive neck lymph nodes at the time of the initial diagnosis appeared to have smaller laryngeal tumors (2.7 cm), compared to with the same group of patients with no recurrence (3.5 cm). Supraglottic location and advanced T stage showed a statistically significant impact on disease free survival, based on Cox regression model. CONCLUSIONS: Smaller sized tumors in patients with locally advanced laryngeal cancer (T4) or regionally (N+) appear to have more aggressive behavior and higher recurrence rate. Thus, the small tumor size could be regarded as an unfavorable prognostic factor for those laryngeal cancer cases.

The value of 11C-5-hydroxy-tryptophan positron emission tomography in neuroendocrine tumor diagnosis and management: experience from one center.

Many neuroendocrine tumors (NET) are small and may escape localization by conventional imaging techniques. In such cases, 11C-5-hydroxy-tryptophan (11C-5-HTP) positron emission tomography (PET) has been tested as an additional diagnostic tool. Nine patients with clinically, biochemically and/or histologically confirmed NET and negative computerized tomography (CT) or magnetic resonance imaging (MRI), and 111In-pentetreotide (Octreoscan) scintigraphy underwent imaging with 11C-5-HTP-PET/CT in order to: 1) detect the primary tumor lesion in three patients; 2) detect residual disease in two patients with appendiceal carcinoid, one with rectal carcinoid, one with midgut carcinoid, and one with ectopic ACTH secretion (EAS) due to residual pulmonary carcinoid; and 3) restage a patient with medullary thyroid carcinoma (MTC) and hepatic metastases. 11C-5-HTP-PET/CT detected lesions in the mediastinum in a patient with EAS due to a pulmonary carcinoid, further hepatic metastases in a patient with carcinoid syndrome (CS) from a NET of unknown primary, further hepatic metastases in the patient with MTC, and hepatic metastases in the patient with midgut carcinoid. The 11C-5-HTP-PET/CT findings contributed to radical cure of the patient with recurrent EAS, and pointed towards bilateral adrenalectomy in the patient with EAS without evident primary tumor. In addition, 11C-5- HTP-PET/CT directed towards combined surgical and medical treatment in the patient with CS and multiple rather than single hepatic metastases and in the patient with midgut carcinoid, and towards continuation of medical treatment in the patient with MTC. 11C-5-HTP-PET/CT is a useful imaging technique, providing additional information for the diagnosis, staging and decision-making regarding management of patients with NET.

Management of the clinically negative neck (N0) of supraglottic laryngeal carcinoma: a systematic review.

AIM: The most effective therapeutic approach for patients with supraglottic laryngeal carcinoma (SGLC) and clinically negative neck (cN0) remains a subject of much debate. The purpose of this systematic review was to answer the following question: among patients with SGLC and cN0 neck, are the survival and occurrence of neck metastases significantly different between patients that received neck dissection and those that had another therapeutic treatment (radiotherapy, combined therapy, 'wait and see' policy)? MATERIALS AND METHODS: An electronic literature search was performed in MEDLINE, EMBASE, Cochrane Library and CENTRAL databases, followed by extensive hand-searching for the identification of relevant studies. The following inclusion criteria were established: the study should (a) include a comparison of neck dissection with one of the other therapeutic procedures for cN0 of SGLC; (b) report the therapy for the initial supraglottic cancer; and (c) use time-to-event analysis of its results. Six studies were eventually identified and systematically reviewed. RESULTS: All studies included in the systematic review were retrospective (n=792 patients). The survival (overall, disease-specific and neck disease-free) and the site of neck recurrence of the patients with N0 supraglottic cancer were not significantly different between patients in the neck dissection treatment group and those of the rest of the therapeutic strategies examined (neck radiotherapy, combined therapy and 'wait and see' policy). CONCLUSIONS: The present systematic review highlights the need for further well-designed prospective studies that will provide more reliable answers to the debatable issue of the management of cN0 of SGLC. Currently, based on the best available evidence, it seems that neck dissection is not superior to radiotherapy or combined therapy or a 'wait and see' policy in terms of survival and control of neck disease.

Fenton and photo-Fenton treatment of a synthetic tannin used in leather tannery: a multi-approach study.

The aim of this work was to compare the behaviour of Fenton and photo-Fenton (UV-A, UV-C) processes to treat synthetic tannin (syntan) used in leather tannery which is one of the most polluting industries, releasing many xenobiotics. Both oxidation processes were performed at pH 3.0 and temperature 40-45 degrees C, which is the original temperature of the re-tanning process, in synthetic solutions containing 100 and 300 mg/L of COD equivalent of syntan. The efficiency of the applied oxidation processes was monitored by chemical oxygen demand (COD), oxidation redox potential (ORP) and aromaticity (UV280) and double bond (UV254) absorbance measurements. Acute toxicity test on Daphnia magna was performed to monitor toxicity in untreated and treated syntan solution. Gas chromatography-mass spectrometry (GC-MS) was applied to identify by-products of partial oxidation occurring in treated samples. The effective ratio of H2O2/FeSO4 for photo-Fenton processes was found to be feasible in terms of reagents used in the process.

Distribution of organotin compounds in the bivalves of the Aegean Sea, Greece.

Five bivalve species--Mytilus galloprovinciallis (Mediterranean mussels), Venus gallina (stripped venus), Modiola barbatus L. (bearded horse mussels), Pecten jacobeus (scallops) and Callista chione (hard clams)--were collected from seven areas in Aegean Sea, Greece, between August 2001 and January 2003 and analyzed for organotins (OTs). The concentrations (as geometric means) found were 17.1 ng g-1 for tributyltin (TBT), 18.8 ng g-1 for dibutytltin (DBT), 7.8 ng g-1 for monobutyltin (MBT) and 13.0 ng g-1 for triphenyltin (TPhT) (wet weight), which are at similar or lower levels than those reported worldwide. Studying OTs distribution between different bivalve species, lower concentrations were observed in mediterranean mussels, possibly due to their growth in water column (grown on sea net pens in mussel farms), in contrast to the free-ranging species, collected from fishing grounds. Concentrations of the OTs in the examined bivalves varied seasonally.

Preoperative evaluation, surgical procedure, follow up and results of 150 cochlear implantations.

BACKGROUND: The cochlear implantation is among the most important achievements of medicine and biotechnology in the last 20 years, because it allows individuals who had never heard or had lost their hearing to perceive sound and improve their quality of life. Selection criteria for candidates are strict and are evaluated in each individual by a scientific committee specially trained for implantations which includes Ear Nose and Throat (ENT) surgeon, audiologist, psychiatrist and speech therapist. PATIENTS AND METHODS: In our department, the first cochlear implantation was performed in 1995. During the last ten years more than 250 individuals have been evaluated due to profound hearing loss and 170 of them were found to be suitable candidates for cochlear implantation. One hundred and fifty (150) have already been operated and most of them are children with congenital hearing loss. No major or permanent complications were recorded in any of our 150 patients. Activation and fitting/mapping of the cochlear implant is initiated three weeks post-operatively. Regular follow-up and mapping of the implant are held, more frequently in children, along with specialized speech therapy. Each new mapping is evaluated according to the record of the patient with regard to the acoustic perception of sounds and speech and the discrimination of individual elements of phonation based on a protocol that we have created for the needs of Greek language. RESULTS: Speech discrimination (AHEPA Hospital protocol), before the Implantation, at the activation of the cochlear implant and till 4 years of the follow-up showed that in our patients, we obtained better and faster results in post-speech acquisition adults with recent or chronic deafness and in children with congenital deafness operated before the 5th year of age, who underwent special preoperative speech therapy programme, fact which is in agreement with current literature. Patient satisfaction evaluated by "Sanders" psychometrics tests, was achieved in accordance to pre-operative expectations. CONCLUSIONS: In our patients, we observed better and faster results in children with congenital deafness operated before the third year of age, in post-speech acquisition adults with recent deafness and in post-speech acquisition adults with chronic deafness but with auditory memory reserve.

Laryngeal tuberculosis presenting as supraglottic carcinoma: case report and literature review.

Laryngeal tuberculosis is a rare extra-pulmonary manifestation of tuberculosis, and frequently presents with tumour-like symptoms and clinical findings. Uncommon clinical features are to be expected by the ENT specialist, who should be aware of these recently changing presentations. Despite the dramatic reduction of the incidence of the disease during the last few decades, a perceptible increase in case reports has lately been noted and may prove significant. Treatment remains conservative and long-term follow-up is suggested. A relevant case of laryngeal tuberculosis presenting as a supraglottic carcinoma is presented, its diagnosis and management are detailed, and suggestions are offered based on a literature review.

Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced non-nasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: The prognosis of patients with recurrent and/or metastatic head and neck cancer (HNC) is poor. Median survival of these patients following chemotherapy is in the range of 6 to 9 months. In the present randomized phase III trial we compared two new combinations containing new drugs with proven activity in phase II studies with patients with HNC. PATIENTS AND METHODS: From November 1999 until November 2004, 166 eligible patients with HNC were enrolled in the study. They were treated with paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8 every 3 weeks (group A, 85 patients) or with paclitaxel, as in group A, and pegylated liposomal doxorubicin 40 mg/m(2) on day 1 every 4 weeks (group B, 81 patients). RESULTS: There was no significant difference in response rate (20% versus 29%, P = 0.21), time to disease progression (median; 4.4 months versus 6.0 months, P = 0.09) and survival (median; 8.6 months versus 11.05 months, P = 0.25). Both regimens were generally well tolerated. The most frequently reported side effect, apart from alopecia, was neutropenia. Overall, there was no significant difference in severe toxicity between the two treatment arms. CONCLUSIONS: The present study could not demonstrate a survival benefit with either regimen. Both treatments were well tolerated. Randomized studies comparing each of the two regimens with standard chemotherapy are warranted.

The deceptive clinical picture of primary saphenofemoral junction aneurysms.

Venous aneurysms may remain undetected for years due to their obscure and non-specific clinical picture. Two cases of primary saphenofemoral junction aneurysm are described, and their vague clinical picture is highlighted. The importance of increased alertness and suspicion is noted, because of the gravity of the possible complications of an undetected venous aneurysm, namely rupture of the aneurysm and/or recurrent pulmonary embolism.

Factors influencing tumour relapse after total laryngectomy.

OBJECTIVES: To determine the prognostic factors predictive of tumour recurrence after surgical treatment for laryngeal carcinoma with total laryngectomy. STUDY DESIGN/METHODS: Retrospective review of 308 patients with laryngeal carcinoma who underwent total laryngectomy in the ENT Department of AHEPA University Hospital between 01/01/1992 and 31/12/1999. In 238 patients, total laryngectomy was performed as primary treatment of laryngeal carcinoma, and in 70 others as treatment of tumour recurrence following radiotherapy or partial surgery. Follow-up was standardized, following a strict protocol, the mean follow-up time was 68 months. RESULTS: During post-operative follow-up, recurrences were observed in 96 of 308 patients (31%). The relapse rates were 27% (65 of 238) for patients treated with primary total laryngectomy, and 44% (31 of 70) for those treated for recurrence following previous treatment. The difference in relapse rates was statistically significant. In 39 of 238 (16%) cases treated with primary total laryngectomy cervical lymph node infiltration was present at diagnosis and radical or modified neck dissection was performed. The tumour recurrence rate in this group was 46% (18 of 39), while in metastatic node-free patients the relapse rate was 24% (47 of 199) [p < 0.05]. Primary laryngectomy was effective in 82% of glottic, 70% of supraglottic, and only 59% of transglottic carcinoma. Concerning primary tumour extension at the time of surgery, total laryngectomy proved effective in 85% of T2 tumours, 81% of T3, and only 55% for T4. The higher recurrence rates for supraglottic and transglottic tumours seem related mainly to the higher rates of cervical lymph node metastasis at diagnosis. The majority of tumour recurrences were observed during the first two years of post-operative follow-up. Thus, 76% of the 308 patients remained disease-free after the first year of post-operative follow-up, 68% after the second year, and 67% after the fifth follow-up year. Of the 96 recurrences documented until now, 91 were loco-regional (19 at the tracheostomy), and only 5 involved distant metastases. Sixteen of the 308 patients (5%) subjected to total laryngectomy have since developed second primary neoplasms, most often involving the lungs (10 patients). CONCLUSIONS: Prognostic factors for recurrence following total laryngectomy include: performance of total laryngectomy as salvage surgery, degree of tumour extension, infiltration of cervical lymph nodes at the time of initial diagnosis, poor initial tumour differentiation and trans-glottic/sub-glottic tumour localization.

Long-term treatment of deep venous thrombosis with a low molecular weight heparin (tinzaparin): a prospective randomized trial.

OBJECTIVES: Evaluation of the effectiveness and safety of the low molecular weight heparin (LMWH) tinzaparin versus unfractionated heparin (UFH) followed by acenocoumarol in proximal deep venous thrombosis (DVT). DESIGN: Prospective, randomized clinical trial. MATERIAL AND METHODS: Consecutive patients (n=108) with acute leg DVT, confirmed by duplex, were randomized to either tinzaparin alone or UFH and acenocoumarol for 6 months. Patients were evaluated ultrasonographically at entry, 1, 3, 6 and 12 months. Thrombus regression, reflux distribution and the incidence of complications were studied. A cost-analysis, comparing the two treatments, was performed. RESULTS: The overall incidence of major events (mortality, DVT recurrence, pulmonary embolism, major bleeding, heparin-induced thrombocytopenia) was significantly different (p=0.035) in favor of tinzaparin (7 versus 17 events). The ultrasonographic clot volume score (an index of recanalization) decreased significantly in both treatment groups. However, tinzaparin produced significantly more extended overall recanalization from 3 months onwards (p<0.02). Thrombus regression was equivalent or in favor of tinzaparin in the different DVT subgroups and venous segments, but the statistical significance varied. Reflux showed non-significant differences overall or in subgroups. A cost-analysis resulted in favor of LMWH. CONCLUSIONS: A fixed daily dose of tinzaparin for 6 months was at least as effective and safe as UFH and acenocoumarol. Regarding major events and recanalization, there was a significant benefit in favor of tinzaparin. Long-term DVT treatment with tinzaparin could represent an alternative to conventional treatment.