Prognostic significance of clinical parameters and Epstein-Barr virus infection in non-endemic undifferentiated carcinoma of nasopharyngeal type: a Serbian report.

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is very rare tumour in Serbia, like in most of the countries of Europe, with incidence less than 0.5 per 100,000 people per year. The aim of this study was to assess the presence of Epstein-Barr virus (EBV) in the UCNT of a non-endemic population in Serbia and identify the main clinical parameters that interfere with patients' survival rate. This study included 102 patients with UCNT who were diagnosed between 1996 and 2003. Biopsies were analysed for EBV-encoded RNA (EBER) by in situ hybridization of tumour tissue microarray. Of 102 patients, 76 were men and 26 were women with ages ranging between 18 and 82 years (median 52.5, mean 53.0±14.1). Survival rates were 80, 39 and 31% for one, three and five years, respectively. Ninety-three of 102 cases were EBER positive (92%). Factors with unfavourable prognostic values were age over 50 years at the time of diagnosis, advanced clinical stage, therapy other than chemoradiotherapy and EBER negative status. In regard to the clinical data, EBER expression in UCNT was shown to be a strong independent predictor of overall and progression-free survival. To our knowledge, the current report constitutes the largest European non-endemic series of UCNT samples from a single institution with correlation between survival and clinical parameters/EBER status.

Computerized rhinomanometry: a study of total nasal resistance normal values.

Computerized rhinomanometry with the practical software programmes is used widely as a research tool to evaluate objectively nasal air flow and resistance parameters, while the increase of its clinical application may be facilitated by further standardization of the method. The aim of the study was to determine the total nasal resistance normal values in healthy adult population using a method of computerized rhinomanometry. A randomized sample of 108 white healthy adults (216 nasal cavities), both sexs with a mean age of 32 (20-45) years comprised the test group. Nasal patency was measured by active anterior rhinomanometry in non-decongested mucosa ("at rest") during 10 repetitive measurements at inspiratory and expiratory reference pressure of 150 Pa. Nasal resistance was measured and calculated according to the recommendations of the Committee on objective assessment of the nasal airway, International Rhinologic Society. The mean total nasal resistance in the sample was found to be 0.179 Pa/cm3/s with the confidant interval from 0,167 to 0,191 Pa/cm3/s at the probability level of 95%. Total nasal resistance was very significantly influenced by sex (t = -4.614), height (F=11.625) and weight (F=11.529) of the examinees. This paper provides additional information on total nasal resistance normal values in healthy adult population important for computirezed rhinomanometry normative parameters standardization.

[Postoperative histopathologic findings in sino-nasal polyposis].

INTRODUCTION: Sino-nasal polyposis is a frequent condition in clinical practice and various pathohistological features that they exhibit can be significant for clinical picture and prognosis of the illness. Aim of this research was to examine pathohistological characteristics of sino-nasal polyposis and according to references from literature to make a pathohistological classification. MATERIALAND METHOD: In the period from May to October 2009. we have analyzed pathohistological characteristics of sino-nasal polyposis in 25 patients. All patients were operated with funcional endoscopic surgery at the Institute of Otorhinolaryngology and Maxillofacial Surgery and pathohistologycal researches were done at the Institute of Pathology, University Medical School of Belgrade. RESULTS: Pathohistological findings in all operated patients confirmed sino-nasal polyposis and classification was establish in following pattern: 16 patients with edematous or eosinophilic polyps (64%), 6 patients with fibro-inflamatory polyps (24%) and 3 patients with hyperplasia of sero-mucous glands (12%). In 3 cases (12%) we have found atypical stromal cells but because of the rest of predominant pathohistological characteristics we did not separate these patients in additional group. CONCLUSION: Edematous or eosinophilic polyps represents predominant pathohistological type which is according to data from literature.

[Analyses of the results in the treatment of locally advanced hypopharyngeal carcinoma with different therapeutic approach].

INTRODUCTION: treatment of locoregional advanced hypopharyngeal cancers of grades III and IV would be surgery and/or radiotherapy. An increasing number of authors has emphasized favorable effects of neoadjuvant chemotherapy and radiotherapy with potentiation. THE AIM: the authors presented therapeutical results of three-year survived patients with squamocellular cancers of the hypopharynx (SCC Hy), grades III and IV, in relation to specific modalities of therapeutical approach. METHODS: a series of 207 patients with grades III and IV of SCC Hy, treated in the period 1982 to 2002, was analyzed. Group I consisted of 131 patients who had surgery and postoperative radiotherapy (SUR-RT). Group II included 16 patients who underwent induction chemotherapy, surgery and postoperative radiotherapy (IC-SUR-RT). Group III consisted of 60 patients, who had primary radiotherapy (RT). Group IV involved 29 patients who were treated, in the period 2003-2006, by neoadjuvant chemotherapy followed by radiotherapy with potentiation (CHT-RT). RESULTS: three-year survival in Group I was 67.94%, Group II--50%, Group III--30%, and in Group IV was 51.72%. Five-year survival was analyzed only in group I-III. The longest survival was observed in Group I--33.59%. CONCLUSION: the best therapeutical results were achieved in patient group that was primarily operated on and then had postoperative radiotherapy, while the worst survival was recorded in patients who had primary radiotherapy.

[Fungal sinusitis diagnostic management and classification].

The aim of this paper is to present the current classification of fungal sinusitis and share our experiences in diagnostic procedures and treatment outcomes. The study includes 31 patients operated since 2000-2009 in whom some form of fungal infection had been dignosed. There were 10 patients with mycetoma, and 16 patients with chronic non-invasive fungal sinusitis, while in five patients allergic fungal sinusitis was proven. All patients were treated postoperatively with topical steroids and irrigation with saline solution, without use of fungicides. Characteristics of chronic non-invasive fungal sinusitis and mycetoma are CT with specific opacification and calcification with involement of maxillary sinus unilaterally or bilateral together with pathohistological finding of positive staining by Grocott with the identification of fungi from secret or tissue. Allergic fungal Sinusitis is characterized by eosinophilia, positive skin test to fungal allergens, elevated serum level of both specific IgE antibodies to causal fungus and total IgE, as well as, pathohistological finding of allergic mucus which include non-invasive hifa. Fungal sinusitis in immunocompetent patients is classified into the following categories: mycetoma, chronic non-invasive fungal sinusitis, chronic indolent sinusitis (which does not occur in our population) and allergic fungal sinusitis.

Overlooked nasal foreign body with a 48-year latent period.

Foreign bodies of the nose are relatively frequent in pediatric population, while in the adults, they are usually seen in disturbed persons. Overlooked nasal foreign bodies may be singled out as a special entity. They become rhinolites over time with latent period of several decades. Our paper illustrates an overlooked foreign body in the nose--i.e. encrusted plastic bead which, after the asymptomatic period of 48 years, induced the unilateral mucopurulent and ichorous secretion from the nose. Rhinolite should be suspected if radiological diagnostics detected calcified mass in the nose together with unilateral nasal symptomatology. Surgical removal of rhinolite results in complete management of such problem. This case indicates the significance of medical history data and examination of nasal cavity in any adult patient with unilateral nasal symptomatology which is refractory to conservative treatment. Computerized tomography of paranasal sinuses is an important adjunct diagnostic tool in indefinite cases. Nevertheless, it often happens that only the extraction of rhinolite indicates the diagnosis that is not usually suspected in adult persons.

[The role of functional sinus surgery for treatment of antrochoanal polyp].

UNLABELLED: Antrochoanal polyp (ACP) is a benign lesion which arises from the mucosa of maxillary sinus, fills it and expands through natural ostium towards choana protruding in the epipharynx. OBJECTIVE: to present our experience in endoscopic surgery of ACP. MATERIAL AND METHODS: prospective study included 24 patients operated at the Institute of Otorinolaryngology and Maxillofacial surgery, Clinical Center of Serbia, Belgrade, in the period 2002-2004. Subjective symptoms, endoscopic and CT findings were evaluated postoperatively, following up the patients in the period 12-20 months. Subjective difficulties of patients were tested by 100mm-analogue scale, while endoscopic and CT findings were demonstrated by three-stage scale from 0 to 2. Applying the technique of ACP extraction in Trendelenburg's position and approaching the part which protrudes in the epipharynx, we successfully removed the endonasal part by means of curved forceps for epipharyngeal biopsy. By endoscopic middle meatotomy, the natural ostium of maxillary sinus was expanded and pathological process from the very sinus was successfully removed. RESULTS: only one female patient had the majority of symptoms after the operation, while all others had no complaints. Endoscopic and CT findings were normal in all patients at the latest control, without any signs of ACP recurrence. There were no intraoperative or postoperative complications. CONCLUSION: minimal damage to sinus mucosa due to forceps is lesser problem than complications developed upon creating even the miniature opening in the canine fossa. Using this technique, a dexterous surgeon may successfully extract patho-logical process with minimal incidence of recurrence, and, more important, with no complications and maximally fast recovery of patients.

[Variations in the surgical treatment of maxillary sinusitis].

From September 2001. to February 2004. in the Institute for ENT and Maxillofacial Surgery were investigated 107 patients with the inflammatory diseases of the maxillary sinuses. Patients with sinusitis were separated into group of patients with rhinogenic (72) and patients with odontogenic maxillary sinusitis (35). We found that the etiology of odontogenic sinusitis was mostly artificial caused after some dental surgery (88%), what is totally opposite to the spontaneous etiology of rhinogenic sinusitis. Surgical treatment of rhinogenic sinusitis mostly was endonasal polypectomy with operation by Caldwell-Luc or FESS. Odontogenic sinusitises were mostly treated by FESS and surgical "closing" of oral-antral fistula by local mucogingival flap (51%).

Patient with double cancer--successfully treated.

INTRODUCTION: Etiology of thrombosis in malignant diseases is multifactorial, and mechanisms that lead to thrombosis include release of the procoagulants from tumor cells (PC), factor related to bed rest, infections, as well as oncological therapy --chemotherapy, hormones, radiotherapy and surgical treatment. Thrombocytosis has frequently been found to be associated with various malignancies. CASE REPORT: 53 years old female patient hospitalised because of hypopharingeal cancer with metastasis in the left neck. Her state was complicated with deep leg vein trombosis and pseudomonas infection. Persistent thrombocitosis in laboratory monitoring indicated more adequate diagnostic procedures, which led to discovering of Chorioidal Malignant Mellanoma as a second cancer. She was treated: surgically, with antibiotics, with anticoagulants and radiotherapy. Patient was discharged from the hospital in good health condition, free of any other symptom of the malignant disease. CONCLUSION: Presense of thrombocytosis and idiopatic thrombosis can suggest occult malignancy. It would be prudent to further evaluate the relationship of trombotic events, trombocitosis and head and neck tumors. We suggest anticoagulants to prevent thromboembolic complications, affect the angiogenesis and prevent development of metastatic disease. It may lead to lower mortality rate.

A comparative study of undifferentiated nasopharyngeal carcinoma treated with radiotherapy or combined treatment with zorubicin-cisplatin and radiotherapy.

Undifferentiated nasopharyngeal carcinoma has been related to the Epstein-Barr virus. These tumors are known to be radiosensitive and chemosensitive. While radiotherapy (RT) allows for a high rate of local control, 80% of all patients die from or with metastatic spread. This study analyzed 61 patients treated with RT alone and 28 treated with zorubicin (ZRB)-cisplatin (CDDP) and RT between 1977 and 1990. All patients treated with RT received 60-74 Gy in 6-7 weeks. Patients treated with combined therapy received ZRB 250 mg/m2 on the 1st day and CDDP 30 mg/m2 from the 2nd to 5th day. The interval between cycles was 4 weeks. Following treatment with chemotherapy patients were then given RT. The 5-year survival rate was 20% for patients with T1 and T2 tumors when treated with RT alone and 54% when treated with chemotherapy (CT). This was 25% for T3 and T4 lesions with RT only and 27% for RT with CT. Survival of patients with N0 and N1 lesions was 41% after RT and 60% after RT with CT. This decreased to 10% for N2 and N3 lesions treated with RT and 30% with RT and CT.

[Respiratory insufficiency and lipomatosis of the neck (Madelung's neck)]. / Respiratorna insuficijencija i lipomatoza vrata ("Madelungov vrat").

A case of Madelungs neck is reported. After two operations in three years the patient developed respiratory insufficiency and transferred to our hospital in state of severe suffocation for tracheotomy. The factors leading to suffocation, such as inspiratory dyspnea, factors influencing the patient to undergo an operation and therapy, and difficulties encountered by an ENT surgeon in managing a respiratory crisis by tracheotomy are highlighted. The reported case illustrates an emergency tracheotomy in a very advanced stage of the disease.

Neck dissection in the management of regional metastases in patients with undifferentiated nasopharyngeal carcinomas.

Residual regional disease after the primary treatment of nasopharyngeal carcinoma is still considered to be a therapeutic problem. The limitations of prophylactic radical radiation, further doses of irradiation as a useful salvage procedure, and the effects on vital structures were the reasons that we employed a therapeutic protocol consisting of radical neck dissection after 40 Gy of radiotherapy and a full tumor dose after surgery. The initial treatment consisted of chemotherapy. Between 1977 and 1991 surgical removal of residual neck metastases was performed in 44 patients with undifferentiated nasopharyngeal carcinomas who had regional metastases at the time of diagnosis. Fourteen patients (group A) had radical neck dissections after initial chemotherapy (using doxorubicin, etoposide, bleomycin and/or 5-fluouracil) and between two courses of locoregional radiotherapy. The remaining 30 patients (group B) were operated on after finishing chemotherapy and locoregional radiotherapy (group B 1) or receiving only full-dose locoregional radiotherapy (group B 2). All patients had histopathologically proven complete remission of primary tumors before neck surgery. The five-year survival rates for group A were 78%, 40% for group B 1 and 27% for group B 2. There were statistically significant differences between groups A and B (P < 0. 01), but not between groups B 1 and B 2. In group A one patient died from subsequent distant metastases and two from local tumor recurrences. Twenty patients died in group B, regional relapses occurred in 40% of the patients in group B 1 and 33% in group B 2, while distant metastases developed in 40% of group B 2. These findings again showed that radical neck dissection was an effective approach for controlling neck disease. When performed after initial chemotherapy and between two courses of radiotherapy, surgery significantly improves the prognosis of patients with positive regional lymph nodes at the time of diagnosis.

[Surgery treatment of laryngeal carcinoma T1]. / Hirursko lecenje T1 karcinoma glasnica.

The early stage cancer of the glottis, including Tis, T1a and T1b stages, are the most common forms with the incidence rates ranging from 25% to 85%. The therapy of early glottic cancer is usually successful for two reasons. First, true glottic cancer produces early symptoms and it is relatively easy to remove. Second, glottis is rather poor with lymph pathways so the regional metastases are rare, less than 1%. Due to role of the larynx in phonation, respiration and swallowing, the cancer of this region and its treatment has a great impact to the quality of life. Retrospective study involved ten-year period, from January 1990 to January 2004. At the Institute for Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, 858 surgical and 54 endoscopic CO2 laser-assisted resections were performed for glottic cancers of larynx of Tis-T2 stages. Glottic tumors were treated by Types III, IV and Va chordectomies according to classificaiton of endoscopic chordectomy defined by the European Laryngological Society. Analyzing the operated patients, as well as the type of the applied surgery, that is, endoscopic-laser and classic surgery, the authors attempted to clarify the dilemmas relating to the indications for one or another type of surgical intervention. The patients who had undergone primary radiotherapy were excluded from the analysis.

[Occult metastases of oral cavity cancers]. / Okultne metastaze karcinoma usne duplje.

Despite new approaches to treatment and lower mortality, malignant tumors of the head and neck, including the malignant tumors of the oral cavity, still represent significant oncological problem because long-term survival has not been significantly prolonged. The growth of tumors of this localization is fast and infiltrative, while early metastases of regional lymph nodes are rather frequent. Malignant tumors of the oral cavity account for 1.1% of population in our community (Dimitrijvic, 2001). The objective of the study was to analyze regional metastases of the cancers of the tongue and the floor of mouth in 101 patients with planocellular cancers treated in the period 1991 to 1995. Clinically positive regional lymph nodes were found in 67.3% of patients, while the most commonly involved regions were submandibular (47.4%) and upper jugular region (46.1%). They were more frequent in localization of the floor of mouth than in case of tongue cancer. Three types of neck dissections were used for surgical treatment of patients. In the group of patients with clinically negative results of the neck (N0) who underwent neck dissection, occult metastases of regional lymph nodes were verified pathohistologically in 19.2% of the time. Malignant tumors of the oral cavity are always the indication for neck dissection, even in N0 category, on account of high proportion of occult metastases.

[Extended supra glottic laryngectomies]. / Prosirene supraglotisne laringektomije.

In the period 1976-1998, 408 patients with supraglottic laryngeal cancer were primarily treated by surgery using the method of supraglottic laryngectomy. Classical supraglottic laryngectomy was performed in 355 patients, while 53 underwent extended supraglottic laryngectomy. The objective of the study was to analyze the success of the extended supraglottic laryngectomy in relation to classical supraglottic laryngectomy in indicated cases. T1 tumor was found in 171 (42%) patients, T2 in 212 (52%), while T3 was found in 25 (6%) cases. Local recurrence developed in 3 out of 53 patients operated by the extended supraglottic laryngectomy technique, and in 17 out of 355 operated by classical supraglottic laryngectomy (chi2=0.075, DF=1, p=0.784; Yates=0.00, p=1.00). Five-year survival of patients operated by the extended supraglottic laryngectomy was reported in 40 out of 53 patients, while survival of patients operated by classical supraglottic laryngectomy was noted in 270 out of 355 cases (chi2=0.004, DF=1, p=0.926; Yates=0.00, p=1.00). There was no significant difference of local recurrence and five-year survival between patients treated by classical and extended supraglottic laryngectomy.

[Modern diagnostic procedures of nasopharyngeal carcinoma]. / Savremene dijagnosticke procedure karcinoma nazofarinksa.

The aim of this study is a research of single photon emission tomography (SPET) values with talium 201 and tehnetium 99m MIBI, comparing it with other methods CT, MRI and ultrasonography. In our investigation there were two groups of patients 24 treated with T1-201 and 17 with Tc-99m-MIBI. Before the therapy 7 patients had been tested with T1 201 and was 100% proved the sensibility, specificity, sensitivity and also 6 patients as really positive TP and 1 patient really negative TN. The same result was gotten in the group where TC 99m was used, where 3 of them were really positive and 1 negative. All discoveries were confirmed pathohistologically and leaning on this we determined the status of really positive and really negative patients. After the therapy there were 7 positive and 7 negative patients, and also one positive, and 2 negatives that were false, who were treated by thalium. On the basis of formula of sensibility these findings show that 77,8%, if it observed only a group of patients who were being tested after the therapy, while all sensibility of methode is 86.7%, where in the analise was included a group of patients at whom was registred the primary tumor. The specificity of the method for this group of patients after the therapy is 87.5%, and the whole 88.9% where the accuarsy is 82.4% in the group after therapy and the whole is 87.5%.

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). TOXICITY: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). TOXICITY: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.