Nuclear texture features for classifying benign vs. dysplastic or malignant squamous epithelium of the larynx.

OBJECTIVE: To search for nuclear features and feature combinations able to assess malignancy and premalignant changes on tissue sections of laryngeal squamous epithelium. STUDY DESIGN: A total of 139 lesions of benign changes (BC) (n = 44), epithelial dysplasias (ED) (n = 50) and invasive laryngeal cancer (LC) (n = 45) were retrieved from archival pathology specimens. The goal of this study was to identify the best features or feature combinations that discriminate BC from LC and also reflect the degree of ED. In order to verify the results on independent data, the groups were split into two separate subgroups, one for training and one for testing. RESULTS: On the test set of slides, the overall correct classification of BC vs. LC cases was 82% using only one feature, fractal2_area. This classification rate could be increased to 91% when a discriminant function based on 10 features was used. However, this gain was not significant. CONCLUSION: Fractal texture features can be used to assess malignancy on tissue sections as an alternative to DNA measurement. In this study feature combinations did not significantly improve classification rates.

Tracheal rupture caused by blunt chest trauma: radiological and clinical features.

The aim of this study was to assess radiomorphologic and clinical features of tracheal rupture due to blunt chest trauma. From 1992 until 1998 the radiomorphologic and clinical key findings of all consecutive tracheal ruptures were retrospectively analyzed. The study included ten patients (7 men and 3 women; mean age 35 years); all had pneumothoraces which were persistent despite suction drainage. Seven patients developed a pneumomediastinum as well as a subcutaneous emphysema on conventional chest X-rays. In five patients, one major hint leading to the diagnosis was a cervical emphysema, discovered on the lateral cervical spine view. Contrast-media-enhanced thoracic CT was obtained in all ten cases and showed additional injuries (atelectasis n = 5; lung contusion n = 4; lung laceration n = 2; hematothorax n = 2 and hematomediastinum n = 4). The definite diagnosis of tracheal rupture was made by bronchoscopy, which was obtained in all patients. Tracheal rupture due to blunt chest trauma occurs rarely. Key findings were all provided by conventional chest X-ray. Tracheal rupture is suspected in front of a pneumothorax, a pneumomediastinum, or a subcutaneous emphysema on lateral cervical spine and chest films. Routine thoracic CT could also demonstrate these findings but could not confirm the definite diagnosis of an tracheal rupture except in one case; in the other 9 cases this was done by bronchoscopy. Thus, bronchoscopy should be mandatory in all suspicious cases of tracheal rupture and remains the gold standard.

Specific changes of chromatin structure in nuclei of normal epithelium adjacent to laryngeal squamous cell carcinoma. A preliminary study of 82 cases.

The aim of this study was to confirm the existence of specific nuclear texture feature alterations of histologically normal epithelial borders nearby invasive laryngeal cancer (NC). Paraffin sections of NC and of chronic inflammations unrelated to cancer (CI) were analysed for nuclear texture and for integrated optical density (IOD-index) and were compared to normal epithelium of patients without evidence of cancer (NE). Several discriminant functions based on nuclear texture features were trained to separate different subgroups. As the most important result, specific nuclear texture feature shifts were only found in NC with high-density lymphocytic stroma infiltrate (NC+). Classification of nuclei of NE versus NC+ was correct in 70%. The same classifier was correct in only 58% when nuclei of NE were classified versus CI. We also found lower values of IOD-Index within the NC+ group when compared to NE (p < 0.001).

[Multiple carcinomas in the upper aerodigestive tract. 1. Oral cavity and oropharynx]. / Mehrfachkarzinome im oberen Aerodigestivtrakt. Teil 1: Mundhöhle und Oropharynx.

BACKGROUND: During the last years an absolute increase of tumour incidence of squamous cell carcinoma as well as an increase in the occurrence of synchronous and metachronous multiple primaries in the upper aerodigestive tract can be observed. This study analyses the so-called "multi-centric cancerization" in patients with primary carcinoma of the oral cavity and the oropharynx. METHODS: During 2 observation periods of 5 years each, from 1985 to 1994, we retrospectively analyzed 235 patients with squamous cell carcinoma of the oral cavity and 232 patients with tumour localisation in the oropharynx. Besides age, sex, tumour localization, TNM-stage and grading, the risk factors tobacco and alcohol were added as causes for the development of multiple primaries. RESULTS: In the primary localisation of the oral cavity synchronous and metachronous double tumours increased from 7% to 17% besides the absolute increase in tumour incidence. In the oropharynx a total increase of second carcinomas from 3% to 20% was found. At the same time a growing abuse of tobacco and alcohol could be observed. CONCLUSIONS: Panendoscopy during pre-therapeutical staging should be obligatory. Regular oncological controls are mandatory, especially for younger patients with smaller tumours and good prognosis, but a high risk of second primaries. In the long run, prevention has to play a decisive role in the fight against second primary tumors of the upper aerodigestive tract. Possible improvements of early diagnosis, genetical examinations, information campaigns as well as research of carcinogenic environmental pollutants are of foremost interest to the clinician.

Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.

PURPOSE: A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION: Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.

[The pT-classification of primary vocal cord carcinomas and its significance for T-classification]. / Die pT-Klassifikation von primären Stimmlippenkarzinomen und ihre Bedeutung für die T-Klassifikation.

Since the pretherapeutic T and pT classification of vocal cord cancer according to the UICC has often been found to fail in a high percentage of cases, frequently resulting in an insufficient separation of the different T categories, the pT classification proposed by Glanz was applied in order to obtain a more exact and better reproducible pretreatment system. In a histopathological investigation of 223 previously untreated carcinomas of the vocal cord dating from 1978 to 1988, specimens from total and partial laryngectomies were examined by subserial sectionings. The extension of each lesion was ascertained by measuring tumor in three dimensions per millimeter and determining affected histopathological structures. Neck lymph nodes were also examined for metastases. The different tumor stages were then evaluated with the UICC T/pT classification of Glanz's pT classification. The survival rates and recurrence-free rates of both classification systems were compared. Our evaluation showed that 24% of all the vocal cord cancers studied had to be classified to a higher tumor stage. The pT classification developed by Glanz was better able to separate the different tumor categories than the UICC T/pT classification. Glanz's pT classification system, staging a glottic cancer according to its exact size and laryngeal structures involved, is a significant improvement on the UICC T and pT classification used to date.

Grading of precancerous laryngeal lesions by multiparameter image analysis at separate epithelial layers.

In order to detect early precancerous changes which do not involve the whole thickness of the epithelium, we used a novel image analysing program based on an IBAS system (Kontron, Germany) to determine nuclear DNA content (NC) as well as average nuclear area (NA) and variation of nuclear area (VA), in the entire epithelium and in three sublayers, parabasal, intermediate, and superficial. DNA aneuploidy was found in only half of the cases classified as 'high-grade' (HG) lesions, comprising carcinoma in situ (CIS) and severe epithelial dysplasias (EDIII), and was chiefly demonstrable in the parabasal third of the epithelium. The other lesions were DNA euploid. HG lesions showed highly significant increases of NA and VA at the lower levels of the epithelium when compared with 'low-grade' (LG) lesions comprising moderate and mild epithelial dysplasias (EDII and EDI). Our data show that the combination of multiparameter image analysis with conventional morphology assists in the objective grading of precancerous lesions and permits the reliable detection of high-grade lesions.

[Further development in TNM classification of laryngeal cancers]. / Weiterentwicklung der TNM-Klassifikation der Larynxkarzinome.

To prepare an improved TN classification of laryngeal carcinomas, a great number of serial sections of laryngeal cancers and neck dissection specimens has been investigated and corresponding studies of clinical relevance were performed. Our proposals have been accepted in the 1993 supplement of the TNM-UICC classification and will be tested within the frame of so-called ramification studies. The authors propose that the T-category of laryngeal carcinomas should no longer be determined by anatomical areas of different sizes, but by millimetres only (up to 15 mm T1, 15-25 mm T2 a, 25 mm and more without impaired mobility T2 b, to impaired mobility or fixation of vocal cords T3, or T4 if the tumour extends beyond the larynx. The pT categories correspond to the T categories. A histological depth of or less than 5 mm is pT 1 or 2. It is proposed that the differentiation into glottic and subglottic tumours of the larynx should be abandoned. In lymph node metastases, the size, number, level and extranodular spread are considered. N1 and N2 are metastases in the upper two thirds of the neck without fixation (extranodal spread). N1 are one or two ipsilateral metastases of 2 cm or less in diameter, N2 are metastases of more than 2 cm diameter or bilateral metastases. N3 are fixed metastases or metastases in the lower third of the neck. Our proposals are presented in tables, ramification tables, conversion tables and a documentation sheet.