Results. One flap failed due to insufficiency of perforators, and two oped a seroma and minor wound rupture. None complained of developed major edge necrosis requiring revisions. Three others were donor site pain or functional problems, but most had some dog-ear re-explored, but salvaged. During the follow-up time one patient has died from the disease, and one is permanently hospitalized. All Conclusions. The anterolateral thigh flap is especially suitable for intra- others have been eligible for follow-up, 12 have reached 1 year. Three oral reconstruction due to its thinness and pliability. The donor morbid- have required minor revisions, debulking or intraoral scar release.
ity is minimal. In our practice, during the last two years, the ALT has All have resumed normal or soft diet. The donor site was closed mostly replaced the radial forearm flap in reconstructions of the head directly in all but one, which was skin grafted. One patient devel- Abstracts from the 17th Annual Meeting of theScandinavian Society for Head and Neck Oncology,Gothenburg, Sweden, 22–24 April 2005 Oral tongue cancer in Finland between 1995 and 1999 Risk Factors and Prognosis in Early Tongue Cancer Ma¨kitie, A.,* Koivunen, P.,† Keski-Sa¨ntti, H.,* Westerborn, A.,* Reizenstein, J.,† Karlsson, M.,‡ To¨rnwall, J.,* Pukkila, M.,‡ Laranne, J.,§ Luukkaa, M.,– ¨ rebro University Hospital, Department of Otorhinolaryngol- *Helsinki University Central Hospital, Helsinki,  Oulu University Hospital, Oulu, àKuopio University Hospital, Kuopio, §Tampere University Hospital, Tampere, and –Turku àO¨rebro University Hospital, Department of Pathology, O¨rebro, University Central Hospital, Turku, Finland Sweden, §Center of Head & Neck Oncology, O Introduction. Management of oral tongue cancer (OTC) remains a chal- lenging problem. The purpose of this study was to investigate the used Cancer of the oral tongue carries a bad prognosis with 30–40% local treatment approach and the outcome of OTC in a nationwide study.
and regional recurrencies even with T1–T2 tumours, Several different Methods. Retrospective clinicopathological data of all patients who were treatment strategies have been advocated without improving survival.
diagnosed for a cancer of the oral tongue between 1995 and 1999 at the Many studies have tried to find prognostic factors influencing outcome five University Hospitals in Finland with a population of 5.2 million inhabitants were reviewed. The mean follow-up time for the whole Method. 1988–2001 we treated 137 patients with cancer of the tongue; 88 patient series was at least 5 years.
patients with T1–T2 tumours are analyzed here. In 1994–95 we changed Results. A total of 235 patients (125 men, 110 women; mean age treatment pattern to do RT postoperatively instead of preoperatively.
61.6 years; range 24–90 years) were included. The T categories were as Surgery was the primary treatment in 43 cases (single treatment in 23 and follows: T1, n = 79; T2, n = 102; T3, n = 38; T4, n = 15. In the major- combined with RT in 20). TNM: T1 (n ¼ 24) and T2 (n ¼ 19). Three ity (77%) of the patients the tumour was located in the lateral border of patients were N+. Forty-five patients did not have primary surgery (40 ext the tongue. Fifty-nine (25.1%) patients presented with neck node meta- RT in combination with surg (n ¼ 21) and brachytherapy (n ¼ 18).
stases. Surgery of the primary tumour was performed in 218 (92.8%) TNM: T1 (n ¼ 8) and T2 (n ¼ 29). Nine patients were N+ (all T2).
patients and in 69 (29.4%) patients consisted of resection of the tumour Results. Forty-three patients had primary surgery (post op external RT with reconstruction of the surgical defect. An ipsilateral neck dissection in 17, brachytherapy in 5) with 11 recurrencies (4 local, 6 regional and was performed in 114 (48.5%) cases and a bilateral neck dissection in 1 locoregional). Forty-five patients were treated with ext RT (40) or nine (3.8%) cases. Pre- or postoperative radiation treatment was given brachytherapy (n ¼ 4) or neck(n ¼ 1). This was combined with to 131 (55.7%) patients. The rate for locoregional recurrences was brachytherapy (n ¼ 14) and surgery (n ¼ 2l). Eleven recurrencies (6 27.8%. Twenty-seven patients (18%) with N0 neck disease had regional local, 4 regional and 1 locoregional). Five patients were never free of recurrences. The 3- and 5-year disease-specific survival (DSS) rates for disease. In group l (surgery) recurrencerate was 26% and in group 2 the whole patient series were 74% and 64% respectively. The 3- and (ext RT) 38%. Of 88 patients 14 were <40 y (3 died of disease), 29 were 5-year DSS rates for stage 1 tumours were 88% and 74%, for stage 2 41–60 y (dod: 7) and 45 were >60 y (dod: 18). Of 29 reexams of surgi- tumours 74% and 62%, for stage 3 tumours 79% and 71% and for stage cal specimens the growth pattern graded 1–2 (n ¼ 21) and 3–4 4 tumours 33% and 33%, respectively.
(n ¼ 8). Grading according to Batsakis, 3–4 is less well delineated.
Conclusions. In the present study the surgical treatment approach seems Tumor thickness: <5 mm 5 pat, 5–9 mm 15 pat, >10 mm 10 pat.
effective in controlling early stage OTC but the frequent locoregional Conclusion. Generally older age groups present with more advanced recurrences and the modest survival, in spite of combined radiotherapy disease. The younger age group does better and usually present with and surgery, point out the need to consider new strategies in the man- less advanced disease. Results indicate that tumour thickness <5 mm is a favourable prognostic sign as is growth pattern 1–2. A reccurence Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400 rate of >40% in the group with tumour thickness 5–9 mm indicate dual ability of specific drugs to accumulate in tumour tissue and to that this group probably should receive more aggressive treatment, transfer light energy to oxygen in the normal triplet state so that it for a especially if combined with growth pattern 3–4. A good and represen- short time converts to highly toxic singlet oxygen.
tative biopsy is necessary for assessing prognosis and treatment Methods. Three different sensitizers were used including Hematoporphy- rin derivative, Porfimer sodium, and Temoporfin. The choice of sensi-tizer was mainly decided by availability. Most treatments were carriedout using a copper vapour pumped dye laser but lately we have used a Brachytherapy of oral tongue cancer: a review of the semiconductor laser, which has simplified the treatment significantly.
Results. Eighty-seven photodynamic treatments for malignant head and Mercke, C.,* Bjo¨rk-Eriksson, T.,* Nyman, J.,* neck tumours were carried out in 52 patients from 1987 to 2004. Sixty-seven treatments were carried out for recurrent or persistent cancer after Hammerlid, E.,† Edstro¨m, S.,† & Fagerberg-Molin, B.‡ radiation therapy failures and 20 were treatments for primary cancer.
*Department of Oncology, University of Gothenburg, Forty per cent of the PDT treatments accomplished a complete response Gothenburg,  Department of Oto-Rhino-Laryngology, (CR) for three months or longer. If treatments, that for any reason were University of Gothenburg, Gothenburg, Sweden, and not adequate are excluded the CR was higher. Patients treated for pri- àDepartment of Oral and Maxillofacial Surgery, University of mary tumours had a better outcome (CR = 65%) than those treated for recurrences. The largest treatment groups were nasopharyngeal cancer(n = 16) and laryngeal cancer (n = 12).
There are several reports of improved local control in patients with Conclusions. In appropriately selected cases PDT can achieve a CR in tumours of the oral tongue following treatment with brachytherapy otherwise untreatable tumours and it can be used to avoid the severe (BT), either alone or in combination with external radiation. The lar- handicap caused by resecting organs such as the soft palate. PDT can gest study of over 600 patients is from Institut Curie in Paris. Most also be used for treatment of recurrent small tumours of the hypophar- patients, who had T1 and T2 disease were treated with an implant ynx and larynx and the technique has a potential for becoming the pri- alone to a dose of 70 Gy over 6–9 days. Large T2 and T3 lesions mary treatment of choice for T1 vocal cord tumours.
received a combination of external radiotherapy and BT. Local controlfor T1, T2 and T3 tumours were 86%, 80% and 68% respectively.
These results are similar to those obtained by Spiro et al., who treatedall their T1, T2 and T3 lesions with partial glossectomy alone. Local Electroporation therapy for cancer in the head and control was in their report 85% for T1, 77% for T2 and 50% for T3 tumours. Another subgroup of patients who seem to have benefited from BT include those who have undergone surgery for small lesions, The Head and Neck Oncology Center, Orebro University yet found to have close pathologic margins, deep muscle involvement, perineural or lymphovascular invasion. When external radiotherapyand BT are combined at least two studies support the concept that in Objective. To review a new selective technique for local ablation of head early stage oral tongue cancer patients the greater the proportion of and neck tumours and to give an overview of the first clinical study in dose given with BT the higher the probability of local control. Most data with BT for oral tongue cancer are derived from treatment with Background. Electroporation, as a means of increasing the permeability low dose rate, LDR. Mostly for radiation protection reasons but also of cell membranes, has been used in basic science since it was discovered for patient convenience, studies with high dose rate, HDR and pulsed in 1974. Erythrocytes exposed to an electrical field started to leak hae- dose rate, PDR, the latter trying to mimic the biology of LDR, are moglobin. The major use today is to introduce genetic material into being performed. In three recent studies results are similar to HDR cells. It has been shown that certain chemotherapeutical agents also can when compared with LDR with respect to local control and morbidity.
be introduced into cells by means of exposing cells in vivo to an electri- In Gothenburg BT has been selected for patients with oral tongue can- cal field (electrochemotherapy). A clinical study has been initiated at the cer during 1995–1999 with the following characteristics: (i) T1-T2-T3 department of Otolaryngology at Orebro University Hospital in conjunc- tumours with insufficient or close margins after surgery = ‘barrier tion with several other hospitals in Europe.
brachytherapy’ and (ii) unresectable tumours, mostly T3-T4, together Method. Both primary and recurrent tumours with a maximum diameter with external radiotherapy and if possible, induction chemotherapy.
of 4 cm can be included in the study. Bleomycin is injected directly into Techniques and results will be described.
the tumour and surrounding normal tissue. After 8–10 min an applica-tor is introduced into the tumour and its surrounding and high voltagedirect current (400–1500 volt, 400 A, 10 ls) is applied between theapplicator needles. The tumour will demarcate from normal tissue after Photodynamic therapy for treatment of malignant about 3 weeks. The anticipated advantage is less damage or destruction of normal tissue and thus less loss of function of vital organs. We do not anticipate increased survival compared with other ablative methods.
¨ rebro University Hospital, Head and Neck Oncology Center, There is a maximized dose of Bleomycin per treatment (80 000 IE) anda lifetime maximum dose of 400 000 IE in this study. Experience has shown that pain can be quite severe but usually does not occur until the Objective. To review a prospective series of patients treated with photo- fifth to seventh day after the treatment. Morphine is effective for pain dynamic therapy (PDT) for recurrent and in some cases primary and Metronidazole may be given to reduce smell from the necrotizing tumours of the head and neck during a period of 17 years.
Background. Photodynamic therapy is an evolving therapy for both pri- Conclusions. A new ablative technique presently is undergoing clinical mary and recurrent tumours of the head and neck. It is based on the Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400 Intensity modulated radiation therapy in the head and Results and conclusions. It was found in the planning study that the SIMT technique could reduce complications in several critical organs, Ba¨ck, A.,* Mercke, C.,† & Johansson, K.-A.* for example parotid glands, mandibles and oral cavity while still give thesame isoeffective doses to the target volumes with increased dose homo- *Department of Radiation Physics, and  Department of geneity compared with the doses created in a combination of external Oncology, Gothenburg University, Sahlgrenska University radiation and BT treatment. However, a clinical study is needed to Introduction. A great deal of experience with radiation therapy of headand neck cancers has demonstrated the need of a high absorbed doseto maximize the probability for local control and thereby cure. In spiteof the development of 3D dose planning it has so far been difficult to The neck diagnosis: diagnostic radiology with CT and protect normal tissue from unfavourable effects with external radiation techniques alone. Interstitial brachytherapy (BT) has good possibilities to accomplish a selectively high dose to the primary tumour but haslimitations, at least for advanced tumours, to be used only as a part of Department of Radiology, Sahlgrenska University Hospital, the treatment and then often as a boost treatment after external radio- therapy. Inverse treatment planning and intensity modulated radiation CT and MR are important in the assessment of head and neck cancer therapy (IMRT) is an alterative approach to the traditional iterative including regional lymph node metastases. Both imaging methods can method of treatment planning. IMRT makes is possible to shape the be used in level classification of pathological nodes. For clinically high dose region so that it conforms closely to the prescribed target known cervical metastases CT and MR can be helpful in demonstra- volume, even for target volumes with concave shapes, and hereby spare ting size, relationship to surrounding tissue, extranodal extension and organs at risk in complex treatment geometries. This leads to a possi- invasiveness. The challenge however is the clinically silent lymph node bility to escalate the absorbed dose to the tumour with minor effects metastases. Apart from identifying deeply sited metastases as in the on the dose to surrounding critical organs which in turn offers an retropharyngeal lymph nodes CT and MR are less successful. The most opportunity to improve local control and survival while at the same reliable imaging criteria of metastases in patients with a known pri- time reducing complications. IMRT also makes it possible to use mul- mary tumour is nodal non-homogeneity or necrosis. The sensitivity tiple target volumes with different prescribed doses for optimization of and specificity of detecting necrosis are approximately 90% in both the dose distribution in the same treatment plan. A planning study CT and MR. In homogeneous sharply outline nodes size is used as a with the purpose to evaluate the impact of the dose distribution of criteria, usually with a maximum allowed diameter of 1.5 cm in level I IMRT planning and treatment of tonsillar carcinoma using simulta- and II nodes and 1 cm in the rest of the neck. Size alone however is neous integrated multitarget treatment (SIMT) is performed. The inaccurate in approximately 25%. Using all imaging criteria, conven- objective is to reduce complications and increase the quality of life for tional CT is found to be slightly better than conventional MR in dem- onstrating cervical lymph node metastases. Imaging upstaging has been Material and methods. The idea with IMRT is to use modulated fluence reported with a wide variation. In order to improve the tissue charac- distribution of the incident beams. The optimal fluence distribution is terization different MR techniques have been attempted such as tissue usually determined using an automated optimization procedure some- specific MR contrast agent and functional imaging with varying times called inverse planning. The dynamic MLC (multi-leaf collimator) technique was used for delivering the fluence modulated beams in thisstudy. Two main advantages wit the IMRT-technique will be used forthe purpose of this study. First of all, the possibility to reduce complica-tions by reducing the dose to healthy tissue and organs at risk, specific-ally the parotid glands and the minor salivary glands in the oral cavity Ultrasound with FNAC and lymphscintigraphy in the and other critical tissues. Secondly, the high dose conformality of IMRT dose distributions will be used to create treatment plans that simulta- neously deliver different dose levels to well defined volumes to do SIMT.
Department of Head and Neck Surgery, Karolinska University We have a long experience in our clinic of combined induction chemo- therapy, external radiation and BT for tonsil cancer patients with goodresults regarding tumour control. However, the frequency of complica- Presence of lymph node metastases is the single most important prog- tions for these patients is high with, for example, xerostomia and in nostic factor in head and neck cancer. If lymphatic tumour spread in some patients’ tissue necrosis. In this study the radiation therapy part of the neck cannot be ruled out, the neck has to be treated. Palpation the treatment will be optimized using the SIMT technique with the alone has a sensitivity of about 50%. With CT and MRI the sensitivity objective to reduce complications and increase the quality of life for the is higher, but even with advanced radiological techniques, 30% of the patients. The aims are (i) to investigate the possibilities of replacing a N+ patients are inappropriately staged as N0 pre-treatment. Ultrasound combined external treatment and a BT treatment with one single IMRT guided fine needle aspiration cytology (Ug-FNAC) has the highest sen- session and (ii) to create a dose gradient around the gross tumour vol- sitivity. In experienced hands the sensitivity is over 70% but this figure ume (GTV) with a specific slope to mimic the differences in radiation varies considerably down to less than 50%. The main reason for our sensitivity and decrease in tumour cell density around the GTV. The difficulties to accurately detect occult metastases of the neck pre-treat- dose gradient was created by defining several target volumes around the ment is that about 25% of the neck metastases are micro-metastases, GTV and delivering prescribed dose levels to those volumes. New target identified only with histopathology after neck-dissection, and they volumes and fractionated schedules for tonsil cancer treatments with the don’t change the structure of the lymph node (impossible to detect SIMT technique were designed using isoeffective dose calculations.
with radiological techniques or to catch with cytology). Another, more Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400 recent prospect to detect occult lymphatic tumour dissemination is Impact on organ preservation, local control and based on growing evidence that metastastic spread is not random but survival with neo-adjuvant/concomitant chemotherapy, a stepwise process. The tumour cells initially propagate to one or two pre-operative radiotherapy and limited surgery for lymph nodes, the sentinel nodes, which primary drain the tumour patients with advanced malignant tumours of the area, and subsequently to other nodes of the neck. Using lymph scin- paranasal sinuses and nasal fossa (MTPSNF) tigraphy, the sentinel node can be identified and biopsied. The resultof the histopathological examination of this node represents the status Bjo¨rk-Erlksson, T.,* Petruson, B.,† Ekholm, S.,‡ Mercke, C.* of the rest of the nodes in 98% of the patients with breast cancer and *Department of Oncology,  Department of Otorhinolaryngo- malignant melanoma where this technique is widely used. In head and logy, and àRadiology, Sahlgrenska University Hospital, neck cancer the sensitivity and specificity of the sentinel node tech- nique is still uncertain. The possible therapeutic implication on bothsurgery and radiotherapy of the neck using the sentinel node technique Introduction. Radical treatment with surgery or radiotherapy (RT) of pa- and individual lymph scintigraphy mapping will be discussed. The tients with advanced MTPSNF is often associated with serious side-effects scientific problem of comparing different patients materials or studies with cosmetic or functional loss. This is a presentation of the impact on that are using different modalities for staging such as palpation only, organ preservation, local control and long term survival with the addition advanced radiological techniques or Ug-FNAC and sentinel node of neo-adjuvant/concomitant chemotherapy (CHT), to pre-operative radiotherapy and limited surgery for patients with advanced MTPSNF.
Methods. From November 1986 to January 2002, 64 patients with meanage 62.3 years (range 21–85) and advanced MTPSNF were scheduled fortreatment with neo-adjuvant/concomitant chemotherapy i.e. cisplatin(100 mg/m2) day 1 + 5-FU (1000 mg/m2) day 1–5, pre-operative radio-therapy (mean dose ¼ 47.9 Gy, range 40, 8–51) and, in responding patients,limited surgery clearing the paranasal sinuses and nasal fossa. Patients New techniques in head- and neck radiotherapy were evaluated with physical examination and CT at regular intervals.
Results. 59 patients completed the intended treatment protocol, one University of Gothenburg, Department of Oncology, patient was Inoperable even at radical dose, one patient interrupted treat- ment due to alcohol abuse and 3 patients died during the treatment inmyocardial infarction, WHO grade 3 and 4 toxicity were seen in ten more Today there is a rapid development of radiotherapy (RT) in the Scandi- patients mainly nausea, infections and renal toxicity. Local recurrence-free navian countries. This development of RT aims at improving the efficacy survival and overall survival at 60 months were 65% and 55% respectively.
i.e. an increased therapeutic gain through both improved definitions of Conclusion. Neo-adjuvant/concomitant chemotherapy with cisplatin + the target volumes and increased conformity/avoidance of normal tissue 5-FU in combination with preoperative RT and limited surgery in and organs at risk (OAR:s). The distinct areas where the development is patients with advanced MTPSNF has resulted in a high rate of organ preservation, local control and survival.
• Imaging for target definition for radiotherapy; CT, MRI, PET, SPECT, Mannose receptor and clever-1 direct the traffic of • RT verification; electronic portal image devices (EPID) cancer cells on the lymph vessel endothelium • RT planning and delivery; CT based dose planning 3 dimensional Irjala, H.,* Alanen, K.,† Gre´nman, R.,* Heikkila¨, P.,‡ conformal RT (3D-CRT), stereotactic radiosurgery (SRS, c-knife- or linear accelerator based), stereotactic conformal radiotherapy (SCRT), *Department of Otorhinolaryngology - Head and Neck surgery, intensity modulated RT (IMRT) 4 dimensional RT (4D-CRT; gating Turku University Central Hospital, Turku,  Department and tumour tracking) and so on and so forth.
of Pathology, Turku University Central Hospital, Turku, • ‘‘New’’ particles; protons and heavier charged particles.
àHelsinki University Central Hospital, Pathology, Helsinki, In head- and neck RT there are well known difficulties to satisfactory §Department of Oncology, Helsinki University Central cover the planning target volumes (PTV) to eradicate the tumour and Hospital, Helsinki, and –Medicity Research Laboratory, avoid dose to the o OAR:s aiming for the best possible quality of life.
These challenging situations include eg 1) a primary tumour in combi- National Public Health Institute, Turku, Finland nation with bilateral neck node (NN) metastases 2) a large pharyngeal Background. Although approximately 50% of cancers give rise to meta- primary tumour in combination with ipsilateral metastatic NN/-s 3) stases via the lymphatic system, the mechanisms mediating this process NN metastases in different levels of the neck and 4) tumours in close vicinity to OARs. Many of the improvements are of particular interest Methods. We investigated the role of two lymphatic endothelial mole- in head- and neck RT since they might help to improve the dose distri- cules, the mannose receptor (MR) and CLEVER-1 in adhesion of malig- bution in situations exemplified above. It is of importance to perform nant cells to the lymphatic endothelium, and analysed their expression randomised studies even when new techniques are introduced in RT.
in two clinical series consisting of squamous cell cancers of the head and However there are relatively few randomised studies of the effect of the neck (n = 17) and breast cancers (n = 72).
introduction of new techniques in RT compared to the introduction of Results. Affinity of the tested head and neck cancer cell lines to the lym- new drugs in medicine. This talk will therefore focus more upon phatic endothelium varied greatly, but adhesion of all cell lines was describing and illustrate some of the new techniques and their potential dependent on both the MR and CLEVER-1. Almost all cancer specimens benefit to the treatment of the neck and finally identify any possible contained peritumoral vessels that expressed CLEVER-1 and the MR, and also the intratumoral lymph vessels often expressed them in both tumour Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400 types. However, only intratumoral expression of these molecules seems to using tumour cell fragment-spheroids as a vector of tumour cells. L-leu- be essential for metastatic spread to the regional lymph nodes. Only eight cine-methylester (LLME), a substance selectively diminishing the secre- (22%) of the 36 axillary node-negative breast carcinomas expressed the tion from TAM in tissue, was added to HNSCC tissue. We were able to MR on the intratumoral lymph vessels when compared with 16 (50%) of establish fragment F-spheroids from malignant and benign tissue from the 32 node-positive carcinomas (P = 0.017), and all eight head and neck HNSCC patients with and without LLME pre-treatment.
carcinoma patients with regional lymph node metastases at diagnosis had Results. F-spheroids treated with LLME showed a significantly decrease in tumours that expressed CLEVER-1 on the intratumoral lymph vessels.
IL-6 production. LLME showed no toxic side effects on the non-TAM cells.
Conclusion. These data suggest an important role for both the MR and Conclusion. TAM is an important factor in the production of IL-6 in CLEVER-1 in directing the traffic of cancer cells within the lymphatic HNSCC and seems to play a supporting role in tumour growth and development. This could have implications for future (immuno-)therapy for HNSCC.
Radiotherapy response in oral squamous cell carcinoma;the importance of apoptotic proteins as prognostic Effects of low-dose cisplatin on Fas (CD95) expression and apoptosis induction in oral cancer cells in vitro Sundelin, K.,* Roberg, K.,† & Ha˚kansson, L.‡ Division of Oto-Rhino-Laryngology, University Hospital, *Otorhinolaryngology, Gothenburg,  Otorhinolaryn- gology, Linko¨ping, and àOncology, Linko¨ping, Sweden Background. Radiotherapy is a primary mode of treatment of squamous Background. New treatment modalities including chemoradiotherapy, im- cell carcinoma (SCC) of the head and neck. Radioresistance and local munotherapy and treatment with selective monoclonal antibodies are recurrence are significant problems following radiotherapy and therefore intensively evaluated for advanced HNSCC. Besides being a potent cyto- it is a paramount need for predictive markers. Loss of growth control toxic drug, cisplatin has interesting immunomodulatory effects. The objec- and a marked resistance to apoptosis are probably major mechanisms tive in the present investigation was to study effects of cisplatin at non- driving tumour progression. Apoptosis is thought to be a critical factor toxic levels on a therapeutically interesting Fas-receptor in oral cancer in radiation-induced cell death, and therefore the importance of apopto- cells, and furthermore, investigate whether apoptosis induction is affected.
sis and apoptotic proteins was studied.
Methods. Two oral squamous cell carcinoma cell lines (UT-SCC-24A and Methods. Cultures from oral tumour biopsies and oral SCC cell lines UT-SCC-20A) were studied. Cisplatin was added to cell cultures at a low were treated with ionizing radiation (15 Gy/3 days). Proliferation and concentration (0.5 lg/mL) and 48 h later Fas expression was studied by cell death were studied by cell counting, apoptosis by detection of immunohistochemical and ELISA techniques. Apoptosis was induced by caspase-3 activity and protein expression by Western blot analysis.
an agonistic Fas-antibody (CH11) and caspase-3 activity was measured.
Results. In cell cultures sensitive for radiotherapy an increase in cell Results. Cisplatin stimulation enhanced expression of membrane-bound death and caspase-3 activity were measured. In tumour cells not sensi- and cytoplasmic Fas in both cell lines as studied by immunohistochemi- tive for radiotherapy three anti-apoptotic proteins, Bcl-XL, survivin and cal staining. However, the total amount of cell-bound receptor was EGFR were expressed in a higher degree compared with cells sensitive enhanced only in UT-SCC-20A according to ELISA results. Furthermore, for radiotherapy. Moreover, the expression of pro- and anti-apoptotic the apoptosis induction was not enhanced by cisplatin in UT-SCC-20A members of the Bcl-2 family differed between the cell lines as well as the whereas in the other cell line (UT-SCC-24A), an enhanced caspase-3 expression of p53 and hsp70 (heat shock protein).
activity was observed after cisplatin stimulation.
Conclusion. Our results suggest that apoptosis and several pro- and anti- Conclusion. Low-dose cisplatin has modulating effects on Fas expression apoptotic proteins play an important role for the radiosensitivity in oral in both cell lines. The results indicate that cisplatin can contribute to re-distribution of cell-bound Fas and thereby enhance susceptibility toapoptosis. Still, other mechanisms, such as p53 status, can play animportant role in cisplatin sensitivity.
Tumour associated macrophages secrete IL-6 withinHNSCC tissueKross, K.W.,* Olsnes, C.,† Heimdal, J.H.,* Olofsson, J.,* & The impact of brachytherapy on quality of life in patients with oral and oropharyngeal cancer *Otolaryngology/Head and Neck Surgery, Haukeland Petruson, K.,* Mercke, C.,† & Hammerlid, E.* University Hospital, Bergen,  Otolaryngology/Head and Neck *Department of Otorhinolaryngology, Head and Neck Surgery, Surgery, University in Bergen, Bergen, Norway Gothenburg, and  Department of Oncology, Gothenburg,Sweden Background. Tumour associated macrophages (TAM) probably play animportant role during tumour establishment, growth, as well as develop- Background. Brachytherapy (BT) is used at Sahlgrenska University Hospi- ment of metastases. It has been shown that the amount of TAM is asso- tal for many tumour sites in head and neck region. BT is most often ciated with a worsened survival rate and neo-angiogenesis. IL-6 is a delivered as a boost after external radiotherapy (ERT) with or without pleiotropic cytokine that modulates a variety of physiological events and preceding surgery or chemotherapy using an interstitial implant with can have a stimulatory function in cancer. IL-6 is a macrophage prod- Ir 192. The possibility to give a higher local dose together with the uct, but is also secreted from head and neck squamous cell carcinoma radiobiologically short treatment time, could well increase patient cure.
(HNSCC) cells. We aimed at determining the source of the IL-6 secreted However, the higher dose and the dose distribution could create side-effects both acute and late, affecting health related quality of life Methods. We have studied the interaction between mononuclear phago- (HRQL). In this prospective longitudinal 3-year study HRQL in patients cytes and autologous head and neck squamous cell carcinoma cells, by with oral and oropharyngeal cancer treated with BT was studied.
Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400 Methods. Two groups of patients were included in the study: 30 patients were taken into account in the TCP analysis. Based on above data, with oral tongue cancer (67% male, mean age 54 years) and 60 patients SIMT–IMRT technique seems to be a better treatment option than with base of tongue or tonsil cancer (79% male, mean age 57 years).
3DCRT + BT for locally advanced nasopharyngeal carcinoma.
Patients’ HRQL was assessed using the European Organization forResearch and Treatment of Cancer Quality of Life Core Questionnaire(EORTC QLQ-C30), and the Head and Neck cancer module (EORTC Screening and rehabilitation of olfaction after total QLQ-H&N35). HRQL was measured at diagnosis and 3, 12 and laryngectomy in Swedish patients: results from an 36 months after the start of treatment. HRQL scores were correlated to intervention study using the nasal airflow- inducing the characteristics of the BT: dose, dose rate, tumour target volume (cm3) receiving doses of 150% and 200%.
Results. After treatment the patients reported statistically and clinically Finizia, C.,* Risberg-Berlin, B.,† & Ylitalo, R.‡ significant problems with pain, problems with swallowing and dry *Department of Otolaryngology, Sa¨rskilda spec. Sahlgrenska mouth. Three years after treatment the oral tongue cancer patients still University Hospital, Mo¨lndal,  Division of Logopedics and reported statistically increased problems with dry mouth. Patients with Phoniatrics, Sa¨rskilda spec. Sahlgrenska University Hospital, base of tongue or tonsil cancer reported statistically increased problems Gothenburg, and àDepartment of Logopedics and Phoniatrics, with dry mouth, eating solid food and problems with choking when swallowing. When correlating HRQL with the BT characteristics onlysingle random correlations were found.
Objective. To examine the olfactory function in Swedish laryngectomized Conclusions. Three years after treatment there still was an impact on patients and to assess the results of the NAIM odour-rehabilitation tech- HRQL, i.e. some treatment related side-effects still persisted.
nique using the validated Scandinavian Odor-Identification Test (SOIT).
Methods. Twenty-four laryngectomized patients, 21 males and threefemales (mean age 68 years) answered olfaction and gustation and qual- 3DCRT combined with brachy-boost contra simulta- ity of life questionnaires and were tested with SOIT before and after four neous integrated multi-target IMRT for nasopharyngeal NAIM rehabilitation sessions.
Results. 72% of the patients with anosmia or hyposmia at baseline carcinoma: comparison of dose distribution and tumour improved during intervention with the NAIM technique according to SOIT results. Before treatment 10 patients were categorized as smellers Taheri-Kadkhoda, Z.,* Pettersson, N.,† Ba¨ck, A.,† while 14 patients were non-smellers, i.e. having anosmia according to Bjo¨rk-Eriksson, T.,* Mercke, C.,* & Johansson, K.-A.† SOIT. Post-inventory, the patients’ with anosmia improved their olfac- *Jubileumskliniken, Department of Radiotherapy, Sahlgrenska tion significantly according to SOIT and their self-estimation of olfac- University Hospital, Gothenburg, and  Department of Radio- tion, gustation and quality of life improved.
physics, Sahlgrenska University Hospital, Gothenburg, Sweden Conclusion. The SOIT odour-differentiation test is an effective and sim-ple test for the assessment of olfaction acuity after laryngectomy in Scan- Objectives. Forty patients with nasopharyngeal cancer (NPC) were trea- dinavian patients. The NAIM rehabilitation method is easy to learn and ted at our centre with a combination of 3DCRT (60–68 Gy/30–34 fr gives rapid and excellent results in improved smell, taste and quality of life. We recommend that olfactory and gustatory rehabilitation accord- (6–12 Gy) ± CHT during 1991–2002. None of patients with T1 tumour ing to the NAIM technique should be incorporated into routine rehabil- (13), developed local recurrence while nine patients (22.5%) of 27 itation program for laryngectomees in Scandinavia.
remaining patients with T2–T4 tumours developed persistent tumour/local recurrence (median follow-up of 45 versus 49 ms) suggesting inad-equate dose distribution using 3DCRT + BT for tumour coverage in loc- Clinical outcome following radiotherapy and planned ally advanced tumours. Through a modelling study, we have evaluated neck dissection in N+ head and neck patients. Is a neck dose distribution advantages of simultaneous integrated multitarget IMRT (SIMT) technique and its impact on TCP of nasopharyngeal Lagerlund, M.,* Ahlberg, A.,† Lundgren, J.,† Lewin, F.,‡ carcinoma compared with combined 3DCRT + BT-boost.
Material and methods. Four patients with following stages (T1N0M0, T1N1M0, T2N2M0, T4N1M0) were chosen for our preliminary analysis.
*Department of Oncology, Karolinska University Hospital, GTV (defined by MRI) and three sets of PTVs as well as 10 different Stockholm,  Department of Otorhinolaryngology, Karolinska organs at risk were delineated and taken into account in the optimiza- University Hospital, Stockholm, àDepartment of Oncology, tion process. For each patient, SIMT–IMRT and 3DCRT plans including Karolinska Universiyt Hospital/St Olavs Hospital, Stockholm/ the dose distribution from the brachytherapy were made. Dose prescrip- tions in SIMT–IMRT for GTV, PTV-T and PTV-N were 72.6, 69.3 and52.8 Gy in 33 fr versus 74 Gy (including HDR-BT 3Gyx2), 68 Gy/34 fr Background. A planned neck dissection (ND) following radiotherapy (RT) is standard procedure in patients with N+ head and neck cancer at Results. Comparing with 3DCRT + BT, SIMT–IMRT plans provided bet- our institutions. In many other centres this is not the case. The aim of ter GTV coverage (V95 = 64–68% versus 98.6–100%) and increased the this retrospective study is to evaluate if unnecessary ND are performed.
TCP for all patients. However, the increase of TCP was dependent on It is a follow-up of our presentation last year in Oulu.
Methods. A review of the medical records in Stockholm between 1998 Conclusions. In this study SIMT–IMRT was superior to 3DCRT + BT in and 2002 was performed. Patients with squamous cell carcinoma of the terms of tumour coverage and increase in TCP. Modest increase in dose head and neck with regional metastases receiving primary RT (60 Gy or per fraction and decreasing the overall treatment time of the tumour more) followed by ND, were included. The follow-up time was between with SIMT–IMRT technique were radiobiological advantages which Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400 Results. A total of 156 patients were included in the study. Recurrence dissection adequate treatment for node positive disease and how high is was found in 29% of the patients. The overall survival was 62% and the disease-free survival 76%. No relation between the palpatory findings in Methods. Since 1988 the Head and Neck Oncology Center at the O the neck after radiotherapy and the clinical outcome was found. Patients University Hospital has a register for head and neck cancer. N+ patients with viable malignant cells in the neck specimen (33%) relapsed in 52% with primary tumours of the oral cavity, pharynx, larynx and salivary compared with 18% if no malignant cells were seen in the neck speci- glands were collected from 1988 to 2001. The data includes surgery, men. Disease-free survival was 48% in the group with malignant cells in radiotherapy, chemotherapy and a follow-up 2004 for recurrences and the neck specimen and 89% in the group with no malignant cells.
Conclusions. In our study ND relieves one-third of the patients from Results. 1058 primary cancers of the oral cavity, pharynx, larynx and viable malignant cells and almost half of these patients survive their salivary glands were classified as N+ in 398 patients. 243 of these N+ head and neck cancer disease. Our clinical examination cannot be used patients had a neck dissection. The follow-up showed 16 patients with as a tool to decide if a ND should be performed or not. Viable malig- recurrence (6.6% ). Six of these patients had a recurrence on the contra- nant cells in the neck specimen after radiotherapy seem to be a strong lateral side of the neck. The other 10 patients are discussed in detail.
negative prognostic factor. Further focus has to be put on this group of Discussion. The overall N-recurrence rate of 6.6% and a side-specific patients. Until further knowledge or better methods for preoperative recurrence of 4% corresponds to the large cancer centres. In the most evaluation are available we do not intend to change our present policy patients we could not find anything indicating that a more radical neck dissection should have been carried out. A scheme for selective neck dis-section is discussed.
Prognostic role of the neck metastasis in patients with Conclusion. Our results compare well with those of others indicating thata more selective and modified approach is safe under the following con- tonsillar carcinoma treated with irradiation ditions. The localization of the primary, the T-classification and the level Aziz, L.,* Grunditz, T.,* Mercke, C.,† Edstro¨m, Staffan* and classification of N+ must be considered before a selective and modi- *Otorhinolaryngology, Head and Neck Surgery, Gothenburg, and  Department of Oncology, Gothenburg, Sweden Background. Tonsillar carcinoma is primarily treated with external radi-ation and brachytherapy in most institutions. Adjuvant neck dissection Malignant mixed tumour of the parotid gland may be performed as well. However, the clinical significance of neck dis- Kontaxis, A.,* Alborno, T.,* Habermann, W.,* section is not secured. The aim of this study was to determine the prog- Salzwimmer, M.,* Beham, A.,† & Rant, B.* nostic significance of lymph node metastasis in patients with tonsillarcarcinoma subsequently treated with irradiation and/or chemotherapy.
*ENT, and  Department of Pathology University Hospital Patients and methods. Ninety-seven patients with carcinoma of the tonsil region confirmed by biopsy from the tumour were treated between 1988 Introduction. Malignant mixed tumours of the salivary gland are and 2000 and followed up at least 3 years at Sahlgrenska University Hos- very rare, representing only 0.2% of all salivary gland malignancies.
pital. All patients were treated with external radiotherapy (final dose 40– Three subtypes of malignant mixed tumours are described: 60 Gy) completed with interstitial irradiation. Sixty patients in this noma ex-pleomorphic adenoma. Carcinosarcoma: this true biphasic group received also chemotherapy before radiotherapy. Thirteen patients cancer consists of malignant epithelial and malignant mesenchymal were subsequently treated with salvage neck surgery when persisting elements. This rare tumour is highly lethal, with a mean patient sur- vival of 3.6 years. Rarest of all is the so-called benign metastasizing Results. Mean age was 61 years. Seventy-six per cent were males and 24% were females. The 3-year survivals in those patients who treated with Case report. We report three cases of carcinosarcoma of the parotid radiotherapy and/or chemotherapy in T stage were T1 87% (n = 11), T2 gland, occurring at our hospital in the last 5 years. Due to this diagnose 89% (n = 28), T3 50% (n = 33) and T4 57% (n = 25). In N stage survi- these patients underwent radical surgery followed by radiotherapy. One val rate was N0 60% (n = 27), N1 70% (n = 11), N2 73% (n = 41) and died in the third postoperative year with extensive local recurrence, one N3 66% (n = 18) respectively. The 3-year survival rates in stage II, III died in the first postoperative year with central nervous system metasta- and IV were 78% (n = 10), 64% (n = 14) and 66% (n = 71). (n = ori- sis, and one is alive and well since 5 years.
ginal number of patients). Survival rates were significantly influenced by Discussion. Carcinosarcoma of salivary gland usually occur in preexisting T stage rather than by other variables (P < 0.01).
pleomorphic adenomas. Tumour spread is characteristically haematogen- Conclusion. This study shows that the survival rate was significantly ous. Tumors metastasize especially to the lung, followed by hilar and influenced by T stage in patients treated with irradiation/chemotherapy.
cervical lymph nodes. Distant metastases were also rarely found in var- As N-state did not have any prognostic significance, we conclude that ious soft tissue sites, bones, liver and the central nervous system.
neck dissection was not justified as an adjuvant therapeutic procedure in Patients were treated with various forms of surgery and occasionally with radiation therapy and/ or chemotherapy. In literature radical surgi-cal excision together with radiation therapy and a neck dissection in case Are neck recurrences more common today when neck of nodal involvement is recommended. The adjuvant role of chemother- dissections are largely selective and modified apy needs to be further evaluated because of the high rate of distant Gertze´n, H.O. & Adamsson, G.-B.
metastasis with these tumours.
Conclusion. Clinical experience of carcinosarcoma of the salivary glands is very poor due to the low incidence of this lesion. This tumour typic- Background. In the literature there has been a lot of discussion about a ally has an aggressive and often rapidly fatal progression. For this reason less radical approach to neck dissection: Is selective and modified neck it is important to keep this patients in a rigid follow up.
Ó 2005 Blackwell Publishing Limited, Clinical Otolaryngology, 30, 384–400


Dilantin kapseals [ipl]

PHENYTOIN DILANTIN 50 MG/mL SOLUTION FOR INJECTION (IM/IV) 1.0 TRADENAME(S) OF THE PRODUCT Dilantin 50 mg/mL Solution for Injection (IM/IV) 2.0 DESCRIPTION Dilantin (phenytoin sodium injection, USP) is a ready-mixed solution of phenytoin sodium in a vehicle containing 40% propylene glycol and 10% alcohol in water for injection, adjusted to pH 12 with a sodium hydroxide. Ph

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