Early effects of different cytostatic protocols for head and neck cancer on oncogene activation in animal experiments.

In vivo investigations on oncogenes and onco-suppressor genes may provide new findings on the potential carcinogenic effects of various cytostatic protocols inducing secondary tumours of the head and neck. Further surgeries are often necessary due to regional recurrence after the Cisplatin-supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol in the treatment of human head and neck tumours. Our earlier studies have illustrated the carcinogenic and mutagenic potential of Cisplatin. The effect of Cisplatin on the alteration of different onco- and suppressor genes has also been proven. Our present study aimed at investigating the early effects of the BVM and the CFu (Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour suppressor gene expressions in mice. Body weight equivalent amounts of cytostatics were administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes were examined. The protocols caused detectable changes. A "short-term" in vivo test, the 24-hour examination of gene expression, is suitable for detecting early effects of carcinogen exposure. The alterations of gene expression, caused by the Cisplatin-containing protocol, draw attention to the probable role of Cisplatin in the development of regional recurrence and to the possibility of prevention.

Early effects of transplatin on oncogene activation in vivo.

The aim of the study was to investigate the early effect of Transplatin (the stereo-isomer of Cisplatin) on oncogenes in inbred CBA/Ca mice. Cisplatin is commonly used for the treatment of squamous cell carcinomas of the head and neck. Cisplatin has a strong oncogene activation effect compared to the structural analogue Transplatin. Body weight equivalent amounts of a human dose of Transplatin were administered intra-peritoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the expressions of c-myc, Ha-ras and p53 genes were examined. Investigation of early changes showed no significant overexpression compared to Cisplatin, which had a significant effect on oncogene expression in the "short-term" in vivo test system.

An effective combined therapy for advanced squamous cell carcinoma of the oral cavity: preoperative BVMM (bleomycin, vincristine, mitolactol plus methotrexate and leucovorin) chemotherapy followed by surgery.

Effects of preoperative chemotherapy with three courses of a combination of bleomycin, vincristine, mitolactol, prednisolone and methotrexate, with a leucovorin rescue, followed by surgery, were studied in 43 patients with advanced squamous cell carcinoma of the oral region. Prior to chemotherapy 32 patients (74%) had advanced T3 or T4 carcinomas whilst 11 patients had T2 lesions. All patients responded clinically to preoperative chemotherapy: 20 patients (46%) achieved clinically complete remission and 23 patients (54%) were judged as partial responders. Sideeffects of this combination chemotherapy were minimal and reversible. Between 15 and 22 days after the last course of chemotherapy the patients underwent surgery, after which 100% were judged to be disease-free. Wound healing complications did not occur. With a median follow-up of 23 months (range 8-45 months), 81% of patients are alive and 79% remain disease free. This combined therapy appears both safe and effective for advanced squamous cell carcinomas of the oral cavity.

A comparative study of preoperative B-V-M-M chemotherapy and irradiation in advanced squamous cell cancer of the oral cavity.

From January 1976, 50 patients with squamous cell cancer of the head and neck were treated with telecobalt preoperative irradiation followed by appropriate surgery. Another group of 50 patients, who matched in risk factors and stage of disease, were treated with preoperative chemotherapy and surgery. Chemotherapy consisted of bleomycin, vincristine, mitolactol and methotrexate. All patients received 3 courses. Surgery was performed 2-3 weeks post-chemotherapy or 4-6 weeks postradiotherapy. Forty-four percent of the patients in the radiotherapy group showed recurrences, while 30% of the patients had recurrence in the chemotherapy group. The overall 3-year survival rate was 66% in the chemotherapy group and 57% in the radiation therapy group, with no statistical difference.

Surgical closures of oropharyngocutaneous fistulas.

Of the 146 patients undergoing surgery for oropharyngeal cancer in our institution, 12 (8.2 percent) developed fistulas. As a first line of therapy, conservative measures were used, which consisted of debridement, Xeroform gauze packing, and nasogastric feeding. Seven fistulas closed after conservative treatment. Of the five patients who required surgery for fistula closure, three had large (more than 20 mm) and two had mid-size (5- to 20-mm) fistulas. In all cases, internal flaps were prepared from the healthy viable tissues surrounding the fistula, and sternocleidomastoid-trapezius-platysma myocutaneous flaps were used for external closure. None of the closures failed, and we obtained good functional and aesthetic results.

Closure of an oropharyngocutaneous fistula in an irradiated patient. A case report.

A case of oropharyngocutaneous fistula is presented in a preoperatively irradiated patient. A double-layer closure, using a modified Owens flap, was used to obtain a satisfactory result.

[Surgical management of oro-cutaneous and pharyngo-cutaneous fistulae]. / Orocutan és pharyngocutan fistulák mütéti megoldása.

Pharyngocutan- or orocutan fistulas have been observed in 8.2% of patients after cancer operations at author's clinic. As first therapy the authors used a conservative treatment, and observed a closure in 7 patients while the remaining 5 patients were operated on. From these 5 last cases 3 had large and 2 had mid size fistulas. Four surgically treated patients had radiotherapy, but after conservative treatment their fistulas showed reepithelisation and lack of inflammatory reaction. These fistulas were closed with internal- and external (double) flaps. In all cases the internal flaps were prepared from surrounding tissues of the fistulas while the sternocleidomastoid-, the trapezius- and platysma-myocutan flaps were used externally.

[Double flap reconstruction of extended facial defects]. / Kiterjedt facialis defektusok kettós lebenyes rekonstrukciója.

The authors report the reconstruction of large facial defects remaining after resection of two advanced facial cancer cases. In both cases double flap closures were carried out. In the first case the internal flap was created from the remaining part of the oral mucosa membrane, while in the second a forearm fascio-cutan free flap was used. For external closure in both cases platysma based transpositional flaps were used, prepared from the neck. On the basis of excellent aesthetic results and safe applicability the authors recommend the more frequent use of this method.

[Comparative study of preoperative chemotherapy and radiotherapy in squamous cell carcinoma of the oral cavity]. / Szájüregi laphámrákok praeoperativ chemotherapiájának és sugártherapiájának összehasonlító vizsgálata.

The results of the preoperative Co 60 irradiation and BVMM (bleomycin, vincristine, mitolactol, methotrexate) chemotherapy were compared. Both treatments were used in 50-50 advanced squamous cell cancer of the oral cavity. The general condition, size of lesion and age of the patients were similar. Surgery in the irradiated group was significantly more radical at the primary sites. Local recurrences during a three-year follow-up period were diagnosed in 36% from the radiotherapy group, whilst 8% such recurrences diagnosed in the chemotherapy group. There was no significant difference in the radicality of lymph node surgery. Lymph node recurrences occurred in 8% from the irradiated group, whilst 22% was diagnosed in the chemotherapy group. The main opinion is that BVMM chemotherapy and irradiation can be used to support one another in the interest of better result, like preoperative chemo- and postoperative radiotherapy.

[Randomized study of cisplatin-based combination chemotherapy for the treatment of planocellular cancer of the head and neck region]. / Kombinált cisplatin-tartalmú kemoterápia randomizált vizsgálata a fej-nyak régióban lévó planocellularis rákok kezelésében.

Between January 1996 and November 1998 38 patients were treated with induction chemotherapy. Patients were distributed in two randomized groups, 19-19 patients in each, receiving (group N) either bleomycin, vincristine and methotrexate (BVM) or the previous medication plus cisplatin (BVCM) chemotherapy (group C). Side effects were low and reversible during the treatments. The clinical regression rate (RR) of the cases was 87% including complete regression 24%. There was no difference between the two groups. There was no difference in the pathological macroscopic regression, however group C was better in microscopic regression. During the 27.5 months of average follow-up time, group N had a significantly better result in the tumor-free survival, with a lower rate of metastatic recidives (N/C = 2/9). There was no significant difference in the overall survival rate, due to the radical neck dissections of recidive metastases. According to our experience we recommend the use of cisplatin in conjunction with neck radiotherapy.

[Incidence of cylindroma in rural dental practice]. / Cylindroma a vidéki fogászati gyakorlatban.

In connection with a case that was misdiagnosed and has been mistreated for 1.5 years, the authors warn that behind a long, uncertain inflammation there might be a tumour as well. They strongly emphasize that each dental examination should be an oncological one at the same time thus helping the dentist in the early recognition of the tumorous disease. The relevant national and international literature is also described in connection with the actual case.

[Etiology of tumors of the oral cavity]. / Szájüregi daganatok etiológiai vizsgálata.

The profession, habit, oral hygiene, residence, sex and age of 100 patients with malignant tumors of the oral cavity are compared with those of 100 control patients. The male, rural population of low culture, smoking habit and regular consumption of alcohol was found to be the most endangered group. A regular check up and enlightenment of this social group is therefore suggested.

[5-year results of combines (radiation and surgical) treatment of intraoral squamous cell carcinoma]. / Szájüregi laphámrákok kombinált (sugaras és sebészi) kezelésének eredményei 5 éves beteganyagon.

Results of the combined (irradiation + surgical) treatment of 33 patients, in great majority with advanced mouth cavity flattened epithelium are reported on. With 45% of the patients a 3 years survival could be obtained. The mainly radical surgical interventions were carried out after big dose preoperative irradiation treatment (Co. 60).

[Lethal complication of an odontogenic infection developing after tooth extraction in a patient with untreated diabetes. Case report]. / Odontogén fertózés foghúzás után kialakult halálos szövódménye egy kezeletlen diabeteses betegben (Esetismertetés).

The extraction of a tooth led to the acute exacerbation of existing chronic osteomyelitis then phlegmon, and sepsis as a result. Persisting coma developed after three reanimations of the patient, on account of septic shock. Finally, in more than two weeks following the extraction the patient died due to multiorgan failure. This case description wishes to call attention to the risks of complications of diabetes, to summarize the relevant documents of diagnosis and treatment of osteomyelitis and phlegmon and the data of mortality. Hopefully we offer some useful advice to the general dentist about patients with immunosuppressive diseases.

Darkening of third molar roots on panoramic radiographs: is it really predominantly thinning of the lingual cortex?

This study investigated the exact intra-alveolar aetiology of a panoramic high-risk sign, darkening of the third molar roots. 83 mandibular third molar surgical removals demonstrating dark bands on the third molar roots in preoperative radiographs were included in this prospective study. Exposure of the inferior alveolar nerve (IAN), the root morphology of the third molar (e.g. groove or hook) and the integrity of the mandibular canal or lingual cortical wall were observed. Differences between single (increased radiolucency alone) and multiple darkening cases (increased radiolucency with accompanying 'high risk' signs) and between IAN exposure and groove formation were analysed. In 38 cases (45.8%), the IAN was visible during the operation. Groove was present in 37.4% of cases. 26.5% of the cases showed lingual cortical thinning, while specious root conformation explained the formation of darkening on the radiographic images of an additional 9.6% of the cases. IAN exposure (P<0.001) and groove formation (P<0.001) were significantly more frequent in multiple darkening cases than in single darkening cases. According to these findings, darkening of the third molar roots is more often the result of fenestration of the inferior alveolar canal wall or groove formation of the root than lingual cortical thinning.

Quantitative pixel grey measurement of the "high-risk" sign, darkening of third molar roots: a pilot study.

OBJECTIVES: Our aim was to examine the panoramic darkening of the root, which is a "high-risk" sign, using quantitative measurements of pixel grey values to determine different aetiological backgrounds, namely inferior alveolar nerve (IAN) exposure with or without groove formation of the third molar roots or thinning/fenestration of the lingual cortex (LCTF). METHODS: 38 impacted third molars that had been surgically removed and had darkened roots on panoramic radiographs were included in this retrospective case-control study. 15 IAN exposure cases were selected for the case group, and 23 cases with proven lingual cortical thinning or fenestration were chosen for the control group. The mean pixel grey values of selected areas in the dark band (D) and control areas within the same roots (R) were determined with the ImageTool (University of Texas Health Science Center, San Antonio, TX) software. The differences in pixel values (R-D) of the IAN and LCTF groups were analysed using the Mann-Whitney U-test and Pearson's χ(2) test. RESULTS: The medians of the R-D pixel values were 45.7 in the IAN group and 34.3 in the LCTF group, whereas the interquartile ranges were 12.0 (IAN) and 18.3 (LCTF) (p < 0.001). The R-D critical value at which the outcomes differed significantly was 38. If the differences in pixel grey values (R-D) were higher than 38, the chance of IAN exposure was approximately 32 times higher than the chance of LCTF (χ(2) test, p < 0.001; odds ratio, 32.0; 95% confidence interval, 3.5-293.1). CONCLUSIONS: The pre-operative prediction of IAN exposure or lingual cortical thinning in cases with "darkening" is possible based on pixel grey measurements of digital panoramic radiographs.

Transgingival lag-screw osteosynthesis of alveolar process fracture.

Fracture of the alveolar process is a common injury. In some cases, traditional fixation may not be possible. The teeth needed for splinting or mandibulo-maxillary fixation may be missing. The fracture line and soft tissue injury may jeopardize the blood supply of the broken bone. In these extreme and rare situations, the best rehabilitation is needed to avoid the loss of hard and soft tissues, and a secondary reconstruction is required. Between January 2003 and December 2006, of 468 cranio-facial trauma patients studied, alveolar process fracture was reported in 28 (6%) cases. In six (1%) cases, the anatomy of the fracture lines, and the position and number of the remaining teeth made splinting and mandibulo-maxillary fixation impossible. Patients were treated with a transgingival lag-screw (TLS) osteosynthesis. All patients healed well with no complications. There was no bone or tooth loss in the surgical area, and broken fragments were not absorbed. The TLS technique is recommended for alveolar fractures when the blood supply is jeopardized and dental splinting or mandibulo-maxillary fixation is not possible. There is no need for flap reflection.

Haemophagocytic sinus histiocytosis with massive lymphadenopathy: early lesions, progression and involution.

In a 26-year-old male suffering from haemophagocytic sinus histiocytosis with massive lymphadenopathy (SHML) five biopsies were performed during a period of 60 months. It seemed that the first change in SHML is the appearance of foamy histiocytes in the subcapsular sinuses at a time when accumulation of and haemophagocytosis by the histiocytes in the intermediary and medullary sinuses are not conspicuous. Progression of the lesions is indicated by the accumulation of haemophagocytic histiocytes in all sinuses and by the development of subcapsular xanthofibrous tissue areas, first focal, later confluent. Regression of the lymphadenomegaly may be due to gradual obliteration of the lymph node parenchyma by the subcapsular xanthofibrous tissue and by scarring. Even in the early phases of the disease the paracortical areas were underdeveloped. The immunophenotype of the foamy histiocytes populating the sinuses and the xanthofibrous areas is S-100+, Leu-M3+, VIM-13+ (CD 14), MAC 387+ N-PNA+, OKIa+, Leu-M1- (CD 15) and OKM1- (CD 11).