Tracheobronchial stents in patients with malignant airway disease: Finnish tertiary care experience.

OBJECTIVES: Tracheobronchial stenting has an established role in the palliation of malignant central airway obstruction (CAO). The purpose of this study is to describe the experience with self-expanding metal airway stents in 2 tertiary referral centres, covering a third of the population of Finland. METHODS: Patients referred to and treated with airway stenting for malignant CAO using self-expanding metal-stents were identified from electronic patient records, and data were collected using a structured Endoscopic Lower Airway Management instrument. Statistical analysis to reveal factors affecting patient benefit and survival was carried out. RESULTS: A total of 101 patients (mean age 65.8) and 116 procedures were identified. Procedure-related mortality was rare (3/101 patients) and complications infrequent. The median survival was 2.3 months [95% confidence interval (CI): 1.4-3.1). Stent benefit was not significantly affected by clinical characteristics. Survival was impacted by the use of adjunct procedures [hazard ratio (HR) 0.36, 95% CI: 0.23-0.58, P < 0.001), procedural urgency (HR 0.40; 95% CI: 0.23-0.71, P = 0.002) and post-treatment chemoradiotherapy (HR 0.29, 95% CI: 0.15-0.56, P < 0.001). CONCLUSIONS: The beneficial impact observed supports the further use of tracheobronchial stenting in malignant CAO. The use of self-expanding metal stents is encouraged.

The Viability and Growth of HaCaT Cells After Exposure to Bioactive Glass S53P4-Containing Cell Culture Media.

HYPOTHESIS: Bioactive glass (BG) S53P4 reduces the viability of epidermal keratinocyte-derived immortalized cell line, HaCaT in sufficient concentrations in vitro. BACKGROUND: Although used in mastoid obliteration surgery, there is no data available on whether BG S53P4 granules have an inhibitory or excitatory effect on keratinocytes, found in normal skin and ear cholesteatoma in vivo. METHODS: HaCaT cell cultures were incubated with a direct BG S53P4 granule contact. Microscopic evaluation of the cultures was performed and interleukin-6 (IL-6) and -8 (IL-8) concentrations were measured from the medium samples. In addition, BG granules were incubated in two cell culture media for 6 days and the pure media were used in confluent HaCaT cultures preceding cell viability assay. Finally, a scratch assay test was performed to reveal the possible BG effect on HaCaT cultures. RESULTS: Eight to ten cell thick layers of dead HaCaT cells were noticed after a 2-day BG granule contact. With a BG concentration of 2.5%, IL-6 and IL-8 concentrations were smaller compared with the control group without BG after 2 days' incubation. Overall, HaCaT cell viability decreased when BG was incubated in keratinocyte growth medium, but did not change in Dulbecco's modified Eagle's medium. In a scratch assay test, cell regrowth in the scratch area was notable in cultures without BG. CONCLUSIONS: BG S53P4 seems to have an inhibitory effect on HaCaT cell growth. Although further studies are needed, this observation seems advantageous for cholesteatoma treatment.

Botulinum toxin alleviates dysphagia of patients with inclusion body myositis.

OBJECTIVES: Oropharyngeal dysphagia is a disabling and undertreated symptom that often occurs in patients with sporadic inclusion body myositis (s-IBM). In this study, we examined the effect of botulinum neurotoxin A (BoNT-A) injections to the cricopharyngeus muscle (CPM) of patients with s-IBM and dysphagia. PATIENTS, MATERIALS AND METHODS: A single-center retrospective study involving 40 biopsy-proven s-IBM-patients treated in the District of Southwest Finland from 2000 to 2013. The incidence of dysphagia, rate of aspirations, rate of aspiration pneumonias and treatment results of dysphagia were analyzed. Patients treated for dysphagia were evaluated before and after surgery by video-fluoroscopy and/or using a questionnaire. RESULTS: Twenty-five of the 40 s-IBM patients (62.5%) experienced dysphagia. BoNT-A was injected a median of 2 times (range 1-7) in 12 patients with dysphagia. Before the injections 7 patients reported aspiration, none afterwards. The corresponding figures for aspiration pneumonia were 3 and 0. All of these patients had normal swallowing function 12months (median, range 2-60) after the last injection. CONCLUSION: BoNT-A injections to the CPM alleviate the dysphagia of s-IBM patients reversibly and appear to reduce the rate of aspiration effectively.

Prophylactic percutaneous endoscopic gastrostomy in head and neck cancer patients: results of tertiary institute.

To evaluate the use and complications of a prophylactic percutaneous endoscopic gastrostomy (PEG) in head and cancer patients in our institute. A retrospective study of 194 consecutive patients with a newly diagnosed upper aero digestive tract malignancy who underwent mainly prophylactic PEG tube placement. The procedure is relatively safe: 15 (7.7%) of the complications were considered serious; no deaths occurred. Of the patients 23 (12.5%) did not use the PEG tube at all, but it was not possible to single out a group of patients in which this could be predicted. The majority of the patients were considered to benefit from the prophylactic PEG insertion.

Bioactive glass S53P4 in mastoid obliteration surgery for chronic otitis media and cerebrospinal fluid leakage.

OBJECTIVES: We evaluated the results of cases of chronic otitis media treated with mastoid obliteration surgery using bioactive glass S53P4. METHODS: Twenty-five patients with chronic otitis media and 1 patient with cerebrospinal fluid leakage without chronic infection were treated with bioactive glass S53P4. Twenty patients had had previous surgery because of chronic otitis media with or without cholesteatoma. A mastoid obliteration was performed with bioactive glass S53P4 granules and a musculoperiosteal flap with or without bone paté. In 2 patients with a bony dehiscence at the middle cranial fossa, a bioactive glass plate was used to support the protruding dura. In addition, in 3 patients, occlusion of a dural fistula was needed The median follow-up period was 34.5 months (range, 1 to 182 months). RESULTS: Excluding the 2 patients with only 1 month of follow-up at our department, 96% of the patients had a dry, safe ear or only intermittent otorrhea. In 92% of the patients, the objective of achieving a smaller or nonexistent cavity was achieved. CONCLUSIONS: Bioactive glass S53P4 is a noteworthy material in mastoid obliteration surgery.

Bioactive glass S53P4 in the filling of cavities in the mastoid cell area in surgery for chronic otitis media.

OBJECTIVES: Chronic infection of the middle ear and cholesteatoma can be treated surgically by exenteration of the mastoid air cells behind the ear. After a procedure with the canal wall-down technique, a cavity remains that is sometimes difficult to clean, collects crust, and becomes repeatedly infected. Such problematic mastoid cavities can be eliminated by filling the created cavity surgically after thorough removal of mucous membranes and cleaning of the bone. METHODS: We treated 7 patients with cavities after canal wall-down surgery for the treatment of chronic suppurative otitis media or cholesteatoma by filling the difficult-to-clean cavity in the mastoid cell area with granules of bioactive glass (BAG) S53P4 to avoid further retraction formation. The area with BAG was carefully closed with a musculoperiosteal flap. RESULTS: After the canal wall-down tympanomastoidectomy, the mastoid cavities were successfully filled in all 7 patients. No biomaterial-associated infection was seen, and no disadvantages for the patients due to the BAG were observed. The cavity in the mastoid cell area decreased in size in all patients treated. CONCLUSIONS: This BAG seems to be a promising material for filling mastoid cavities after canal wall-down tympanomastoidectomy.

Parotidectomy in the treatment of pleomorphic adenoma -- analysis of long-term results.

CONCLUSION: Parotidectomy is an efficient surgical treatment modality for pleomorphic adenoma of the parotid gland, although some morbidity may occur. In this study, the median time interval between primary surgery and the presentation of the recurrent tumor was observed to be 14.4 years. OBJECTIVE: Analysis of the long-term results of patients undergoing lateral or total parotidectomy as first-line treatment of parotid pleomorphic adenoma at our institution between the years 1979 and 1996. METHODS: The individual patient charts of 230 patients were feasible for retrospective analysis in 2007. RESULTS: In all, 42 patients had dysfunction of the facial nerve after the primary surgery, but only 14 of them had permanent dysfunction. A recurrent tumor occurred in nine cases (3.9%). The time interval between primary surgery and the first recurrence ranged from 7.1 to 24.5 years. Recurrent tumors were treated with surgery, two patients received additional radiotherapy.

Signaling via ErbB2 and ErbB3 associates with resistance and epidermal growth factor receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells.

PURPOSE: The epidermal growth factor receptor (EGFR) inhibitor gefitinib (Iressa) has shown antitumor activity in clinical trials against cancers, such as non-small cell lung cancer and head and neck squamous cell carcinoma (HNSCC). Research on non-small cell lung cancer has elucidated factors that may predict response to gefitinib. Less is known about molecular markers that may predict response to gefitinib in HNSCC patients. EXPERIMENTAL DESIGN: We analyzed possible associations of responsiveness to gefitinib with molecular markers of the EGFR/ErbB receptor family signaling pathway using 10 established HNSCC lines in vitro. IC50 of gefitinib sensitivity was determined using clonogenic survival assays. ErbB signaling was assessed by Western and real-time reverse transcription-PCR analyses of EGFR, ErbB2, ErbB3, and ErbB4 expression levels as well as by phosphorylation analysis of pEGFR, pErbB2, pErbB3, pAkt, and pErk. EGFR sequences encoding kinase domain and EGFR gene copy numbers were determined by cDNA sequencing and real-time PCR, respectively. Finally, responsiveness to gefitinib was compared with responsiveness to the anti-EGFR antibody cetuximab (Erbitux). RESULTS: Expression levels of pErbB2 (P = 0.02) and total ErbB3 protein (P = 0.02) associated with resistance to gefitinib. Combining gefitinib with pertuzumab (Omnitarg), an antibody targeting ErbB2 heterodimerization, provided additional growth-inhibitory effect over gefitinib alone on relatively gefitinib-resistant HNSCC cell lines. The same markers did not predict resistance to cetuximab. In contrast, a similar trend suggesting association between EGFR gene copy number and drug sensitivity was observed for both gefitinib (P = 0.0498) and cetuximab (P = 0.053). No activating EGFR mutations were identified. CONCLUSIONS: EGFR amplification may predict sensitivity to gefitinib in HNSCC. However, other EGFR/ErbB receptor family members than EGFR may contribute to resistance to gefitinib. ErbB2 and ErbB3 may have potential as predictive markers and as therapeutic targets for combination therapy in treatment of HNSCC with gefitinib.

Oropharyngeal carcinoma and its treatment in Finland between 1995-1999: a nationwide study.

The survival figures for advanced stage oropharyngeal carcinoma (OPC) have remained moderate in spite of radical combined modality treatments. The purpose of this study was to investigate the used treatment approach and the outcome of OPC in a nationwide study. Retrospective clinicopathological data of all patients diagnosed with OPC between 1995 and 1999 at the five university hospitals in Finland were reviewed. All patients had a minimum 4-year follow-up. A total of 168 patients (145 men and 23 women, mean age 59 years; range 28 - 89 years) were included. The T categories were as follows: T1, n =34; T2, n =55; T3, n =40; T4, n =39. One hundred and seventeen (69.6%) patients presented with neck node metastases and three (1.8%) patients with distant metastases. In the majority (61.3%) of the patients the tumor was located in the lateral wall of the oropharynx. In 144 (85.7%) patients the treatment was performed with curative intent. Of these, surgery of the primary tumor was performed in 123 (85.4%) patients, and the defect was reconstructed with a pedicled flap or free tissue transfer in 66 (53.7%) of these patients. A neck dissection (ND) was performed in 86 (69.9%) out of these 123 cases. Surgery was the only treatment modality in 10 (6.9%) patients. Radiation therapy (RT) only (with or without chemotherapy) was given to 21 (14.6%), combined treatment with surgery + radiation therapy (S + RT) to 110 (76.4%) and surgery + chemoradiotherapy (S + CRT) to 3 (2.1%) patients. Overall (OS) 3- and 5-year survival rates were 58 and 45%, respectively. Disease-specific (DSS) 5-year survival rates by T-class for the patients treated with curative intent were as follows: T1, 77%; T2, 70%; T3, 66%; T4, 53%. The variable treatment approach, the frequent locoregional recurrences and the moderate survival point out the need to consider new strategies in the management of OPC.

Hypopharyngeal carcinoma in Finland from 1990-1999.

Data concerning the diagnosis, treatment and clinical course of patients with hypopharyngeal carcinoma (HPC) in all five university hospitals in Finland between 1 January 1990-31 December 1999 were retrospectively analysed. During the study period, 149 HPC cases were diagnosed in 111 men and 38 women (74%/26%), with a mean age of 64.5 years. At the time of diagnosis, 6 patients (4%) had stage I, 11 (7%) stage II, 32 (22%) stage III and 100 (67%) stage IV disease. In 74 (49%) cases, the primary treatment was surgery. Pre- or postoperative radiation therapy was given to 67 patients. Radiation therapy was the primary treatment in 47 (32%) patients, and 12 patients (8%) received concomitant chemoradiation. The overall 5- and 10-year disease specific survival (DSS) was 22 and 13%, respectively. The 5-year DSS was 66% for stage I, 59% for stage II, 31% for stage III and 12% for stage IV disease. In the three major treatment groups, i.e., surgery and radiation therapy, radiation therapy alone and concomitant chemoradiation, the 5-year DSS were 32% for surgery and radiation therapy, 7% for radiation therapy alone and 38% for concomitant chemoradiation. Prognosis of HPC remains poor, especially in the more advanced stages of the disease. In addition to traditional surgery and radiation therapy, concomitant chemoradiotherapy seems to give equal results in tumor control, thus making organ preservation possible in the primary treatment of HPC.

Early percutaneous endoscopic gastrostomy nutrition in head and neck cancer patients.

OBJECTIVE: Many head and neck cancer patients suffer from poor nutrition. Nutrition is a problem during and after therapy, especially when it consists of extensive surgery, intensive (chemo)radiotherapy or their combination. Additional enteral nutrition has been provided by means of either nasogastric tube feeding, surgical gastrostomy, radiologic percutaneous gastrostomy or percutaneous endoscopic gastrostomy (PEG). Because of the straightforward, easy technique involved and its low complication rate, PEG has become established as the primary route of nutrition in these patients. Previously, the aim of assisted enteral nutrition was to compensate for already existing malnutrition; nowadays, an additional purpose is to diminish or prevent the development of malnutrition. The main objective of this study was to evaluate the safety of pre-treatment PEG in a sample of patients with an upper aerodigestive tract area malignancy treated in a tertiary referral centre. MATERIAL AND METHODS: A total of 79 patients with an upper aerodigestive tract area malignancy were treated with a total of 80 PEGs during the period 1997-2001. RESULTS: Most of the PEGs (62/80; 77.5%) were performed by an otolaryngologist. An open gastrostomy was needed in five cases because of unsuccessful gastroscopy due to oesophageal stricture (n=4) or severe trismus (n=1). Both acute and late complications were minor and the respective complication rates (1/80; 1.3% and 12/80; 15%) were low. In addition, all complications were easily managed and did not seriously affect the actual treatment. CONCLUSIONS: A major advantage of having the PEG performed by the otorhinolaryngologist was the possibility to combine it easily with other necessary procedures, such as panendoscopy, tracheostomy and additional biopsy. In addition, the timing of the procedure was easy to schedule.

Ultrasonically activated scalpel compared with electrocautery in tonsillectomy.

The occurrence of postoperative bleeding, the quantity of operative bleeding and the duration of operation were retrospectively evaluated in 407 patients who underwent tonsillectomy within a 32-month period. They were operated on with either an ultrasonically activated scalpel (UAS), bipolar diathermy (BPD) or blunt dissection with monopolar diathermy (MPD) with the following results. (1) Primary bleeding was more common with MPD: MPD 7.1% vs. BPD 2.4% (p < 0.01) vs. UAS 1.0% (p < 0.001). Secondary bleeding was more common with UAS: UAS 19.6% vs. MPD 14.5% (p < 0.001) vs. BPD 14.5% (p < 0.01). There was no statistical significance in the differences between overall postoperative bleeding rates. (2) There was statistically significantly less operative bleeding with UAS:UAS 24.8 ml vs. MPD 58.7 ml vs. BPD 43.8 ml. (3) On the other hand, the operation time was on average longer with UAS: UAS 32.3 min vs. MPD 18.4 min vs. BPD 22.1 min. Our results suggest that UAS offers no significant advantage over MPD or BPD in tonsillectomy other than minimal operative bleeding possibly due to longer duration of operation.

Concomitant vinorelbine and radiation in head and neck squamous cell carcinoma in vitro.

Concomitant chemoradiotherapy has been used for locally advanced head and neck squamous cell carcinoma (HNSCC) particularily with cisplatin, 5-FU, methotrexate, bleomycin and taxanes. Vinorelbine is a semisynthetic vinca alcaloid, which causes a block in the G2/M phase of the cell cycle. HNSCC cell lines have previously been reported to be sensitive to vinorelbine in nanomolar concentrations. In the current study the effect of vinorelbine as a radiosensitizer in vitro was studied and eight recently established head and neck SCC cell lines of the UT-SCC-series were tested. Vinorelbine concentrations of 0.4-1.6 nM were used, corresponding to the IC70, IC50 and IC30 values of each cell line, resulting in 30%, 50% and 70% inhibition in clonogenic survival. The desired concentrations of vinorelbine were added to the medium and the cells were plated in 96-well culture plates in this solution. The plated cells were irradiated 24 h later with 4MeV photons generated by a linear accelerator and incubated at 37 degrees C with 5% CO2 for 4 weeks. Thereafter, the number of wells containing coherent, living colonies, consisting of 32 cells or more, was counted. The plating efficiency was calculated and the fraction survival data were fitted to the linear quadratic model [F = exp[-(alphaD + betaD2)]]. An additive effect of combining vinorelbine and irradiation could be demonstrated. The dose-dependent decrease in survival was seen at vinorelbine doses of 0.4-1.6 nM in all cell lines tested.

Intraluminal radiotherapy in esophageal cancer. An update.

Oesophageal cancer is severe illness leading usually to death. Radical surgery is the most successful treatment but most patients are not operable at the time of diagnosis. For these patients external beam radiotherapy with or without concurrent chemotherapy offers the best choice for cure or palliation. In patients with advanced oesophageal cancer, intraluminal brachytherapy has been proposed as an additional method to increase local control. Between 1989-2002, 49 patients with inoperable oesophageal cancer were treated with combined external and intraluminal radiation therapy in Turku University Central Hospital. The external radiation was performed with a median total dose of 40 Gy given in 20 fractions. On the average a week after the external radiation a median total dose of 10 Gy intraluminal radiation therapy was given in 4 fractions. The intraluminal brachytherapy could be performed without technical difficulties and no major complications were seen. In many cases (twenty out of 49 patients, 41%), the symptoms could be relieved immediately and in most cases the progression of the disease could be delayed. The one and two year survival rates were 30% and 18%, respectively. All patients alive at two years can be considered as long-time survivors. Median follow-up was 86 months. Intraluminal brachytherapy is a safe and efficient treatment modality which offers a potential means of cure for selected patients with oesophageal cancer.

Endoscopic lasersurgery in obstructive tracheal and bronchial tumors. An update.

Endobronchial tracheal and bronchial obstructive tumors cause severe breathing impairment and may lead to death if the airway can not be maintained. Endoscopic laser surgery is one method to treat these patients. In this study the results of one tertiary care university hospital are analyzed. In the years 1987-1999, in Turku University Hospital, 102 patients were treated with 270 laser treatment sessions, 89 of them for a malignant and 13 for a benign disease. In the years 2000-2002 34 patients were treated in 65 laser treatment session, 21 for a malignant and 13 for a benign disease (Group B). Treatment was performed mostly with a combo CO2-Nd:YAG laser via a rigid bronchoscope, but also a CO2 laser and a fiberoptic Nd:YAG laser were used. The treatment was considered successful in 208 cases of 270 treatment sessions (77%). The most important single factor affecting the success of the therapy was the unfavourable location of the tumor (40 cases). In these cases the tumor was either located too distally in the bronchial tree, or the airway obstruction was found to be caused by extraluminal compression. There were two fatal complications (0.7%). Minor intraoperative bleeding occurred in 7.4% (20/270,) and intraoperative ventilation problems in 7.0% (19/270). In Group B there were one fatal complication (1.5%). Minor intraoperative bleeding occurred in 5 treatment session (7.7%). There were no complications when treating for benign disease. The one-year survival of the patients with malignant disease was 37.1% (33/89), the two-year survival 20.2% (18/89) and the five-year survival 9.0% (8/89). Laser treatment is an effective method in maintaining tracheobronchial ventilation as a palliative treatment modality. Serious complications are possible, but considering the fatal nature of the disease, they must be accepted. In cases of benign diseases, endobronchial laser treatment was very successful.

Head and neck squamous cell carcinoma cell lines are highly sensitive to the new taxanes, BMS-184476, BMS-188797, in vitro.

BACKGROUND: The development of synthetic taxanes targets at increasing solubility of the drug, improved clinical efficacy and reduced side-effects. We evaluated the sensitivity of head and neck squamous cell carcinoma cell lines to BMS-184476 and BMS-188797 in vitro. MATERIALS AND METHODS: The effects of paclitaxel and the synthetic taxanes were tested on six recently established cell lines (3 oral cavity SCC, 3 laryngeal SCC) using the 96-well plate clonogenic assay. The IC50 values, corresponding to the mean inactivation dose, were obtained from the dose response curves. RESULTS: All tested cell lines were considerably more sensitive to both synthetic taxanes compared to paclitaxel. As a rule, the IC50 concentration for paclitaxel was 4-5.5 times higher than that of BMS-184476 or BMS-188797. The sensitivity to these drugs varied from cell line to cell line, and time lapse video microscopy showed a mitotic arrest with subsequent apoptosis after four hours with BMS-188797. CONCLUSION: These results indicate that the synthetic taxanes could be useful clinically and warrant in vitro testing in combined modality models, like concurrent chemoradiation.

Cervical metastasis of unknown origin: a series of 72 patients.

Cervical metastasis of unknown origin is still a challenging problem because of its relatively poor prognosis and the uncertainty regarding the primary site. We analyzed retrospectively all 72 patients with cervical metastases of unknown origin, diagnosed and treated between 1985 and 1995 in the five university hospitals of Finland in order to analyze survival rates and some prognostic and clinical factors of the disease. The most common sites where the primary tumor was found during follow-up or at autopsy were the lung (8%), the oral and pharyngeal region (7%) and the skin (6%). When the lower neck nodes (regions IV-VI) were affected, the primary tumor was significantly (p < 0.001) more often found from the subclavicular sites. The disease-specific 5-year survival rate was 32%. In multivariate analysis, nodal stage N2c or N3 [adjusted relative hazard of death (HR) 2.43], other metastases found at the time of treatment (HR 2.15) and age > 65 years (HR 2.12) were significantly associated with a poor prognosis. Median survival tended to be longer for patients treated with surgery combined with radiotherapy (39.9 months) compared with those treated with radiotherapy alone (16.8 months), but this difference was not statistically significant (p = 0.153).

Neodymium YAG contact laser in the treatment of cancer of the mobile tongue.

The aim of this study was to evaluate the usefulness of a contact neodymium YAG laser for the treatment of squamous cell carcinoma (SCC) of the mobile tongue in 35 patients. The TNM stage and histologic grade were as follows: T1, n = 20; T2, n = 11; T3, n = 4; and N0, n = 33; N1, n = 2; G1, n = 20; G2, n = 10; and G3, n = 5. The surgical treatment consisted of a hemiglossectomy or resection with adequate margins in 28 cases, and an ipsilateral neck dissection was also performed in 7 patients. Radiotherapy to a mean tumor dose of 62-64 Gy and an elective dose of 50 Gy to the cervical lymph nodes was given to 14 patients. The radiotherapy was preoperative in 12 patients and postoperative in 2. Tongue resection was easily performed using the contact neodymium YAG laser, with a mean operation time of 31 min and intraoperative bleeding varying from negligible to 100 cm3. During postoperative follow-up no major complications occurred: cases with minor hemorrhage were easily controlled on the ward and 1 patient had a bleed on the 14th postoperative day necessitating hospitalization. The resection was histologically radical in all cases. During follow-up one patient had a local recurrence (T2N0, G3) and four failed in the neck (T1N0 G2, T1N0 G2, T1N0 G2, T2N0 G2), three of whom were successfully salvaged with a neck dissection and radiotherapy. One patient with osteoradionecrosis was diagnosed and treated curatively. Two patients died of their tongue cancer (T2N0 G3, T2N0 G2), 1 died from a second primary tumor (T2N0 G1) and 2 of intercurrent disease with no evidence of cancer; 30 patients (86%) are still alive with no evidence of disease. The function of the tongue in all patients in this sample was good to satisfactory. The major complaint was xerostomia in the irradiated patients. In conclusion, the contact neodymium YAG laser appears to be suitable for resection of T1-T2 SCCs of the oral tongue. In this limited patient sample T stage or grade did not predict failures in the neck. Biologic predictive markers need to be evaluated.

Paclitaxel combined with fractionated radiation in vitro: a study with vulvar squamous cell carcinoma cell lines.

Concurrent paclitaxel and radiation has given promising results in the treatment of a variety of solid tumors. We wanted to test the efficacy of this combination for vulvar carcinoma, which currently has a poor outcome in advanced stages. The radiation sensitivity, sublethal damage repair (SLDR) capacity and effect of paclitaxel during fractionated radiation were assessed in our study on 7 vulvar inherently radioresistant squamous cell carcinoma (SCC) cell lines. The 96-well plate clonogenic assay was used. Survival data were fitted to the linear quadratic model. The area under the curve (AUC), equivalent to mean inactivation dose (D), was obtained with numerical integration. AUC ratios between single-dose radiation and fractionated radiation with or without paclitaxel were used to determine the SLDR of the cell lines and the effect of paclitaxel on it. Seven currently tested vulvar SCC cell lines were found to have a limited capacity of repairing sublethal damage (SLD). Only 3 of them presented SLDR of significance. The effect of concurrent radiation and paclitaxel was clearly additive when the radiation dose was fractionated in most of the cell lines. In addition, 2 of the cell lines having SLDR exhibited a trend toward losing the repair capacity when paclitaxel was present during the irradiation. In addition, the survival curve of the UM-SCV-1A cell line gave the impression of a true paclitaxel effect on SLDR. Paclitaxel used concurrently with fractionated radiation showed effectiveness on vulvar carcinoma. The effect was at least additive and could even be expected to abrogate the SLDR during split-dose radiation.

Head and neck squamous cell carcinoma is highly sensitive to vinorelbine in Vitro.

The vinorelbine sensitivity of eight recently established head and neck squamous cell carcinoma (SCC) cell lines was tested using the 96-well plate clonogenic assay. The chemosensitivity of these head and neck SCC cell lines to vinorelbine expressed as IC50, corresponding to the drug concentration causing 50% inhibition in clonogenic survival, varied between 0.6 and 1.0 nM. The dose-dependent growth inhibition caused by vinorelbine was measured in three of these cell lines. A clear growth inhibition was observed at a concentration of 3 nM. The same cell lines were studied with flow cytometry. When exposed to 3 nM and 5 nM vinorelbine, an accumulation of the cells in the G2/M-phase was observed in all cultures after 12 hours. The morphological changes induced by 3 nM and 5 nM vinorelbine to the UT-SCC-33 cell line were analysed with time-lapse video microscopy. In the cultures treated with 5 nM vinorelbine, the cells stayed mitotically arrested for 2-32 hours and thereafter died morphologically by apoptosis. These results indicate that, in vitro, the head and neck SCC is consistently sensitive to vinorelbine, which blocks the cell cycle in G2/M, the most radiosensitive phase. These encouraging results suggest that vinorelbine may potentially be used in conjunction with radiotherapy in the treatment of head and neck SCC.