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Biomedical subjects

R Koole

Publications and source records attributed to R Koole.

At least 37 records · Page 2Linked to original sources

Preoperative evaluation of patients with primary head and neck cancer using dual-head 18fluorodeoxyglucose positron emission tomography.

OBJECTIVE: To evaluate the value of 18fluorodeoxyglucose (FDG) positron emission tomography (PET) in primary head and neck cancer. BACKGROUND DATA: Head and neck carcinomas tend to metastasize to regional lymph nodes rather than to spread hematogenously. With nodal metastases, cure rates decrease by approximately 50%. Moreover, in approximately 3% of the patients, a second primary tumor is found at initial presentation. METHODS: Fifty-four consecutive patients (31 men and 23 women; mean age 60 years, range 34-81 years) with previously untreated squamous cell carcinomas of the oral cavity or oropharynx were studied. Before surgery and within a period of 3 weeks, clinical examination, chest x-ray, computed tomography (CT), ultrasonography with fine-needle aspiration cytology (US/ FNAC), and FDG-PET were performed. All study results were scored per neck side and were also classified as 0 (no metastases), 1 (single metastasis), or 2 (multiple metastases). RESULTS: The sensitivity for the detection of lymph node metastases per neck side was 96%, 85%, and 64% for FDG-PET, CT, and US/FNAC, respectively. The specificity was 90%, 86%, and 100% for FDG-PET, CT, and US/FNAC, respectively. In terms of the classification, FDG-PET showed the best correlation with the histologic data. Finally, in nine patients (17%), a second primary tumor was detected by FDG-PET and confirmed by histologic evaluation. CONCLUSION: Because of the high prevalence of second primary tumors detected by FDG-PET and the decreased error rate in the assessment of lymph node involvement compared with CT and US, FDG-PET should be routinely performed in patients with primary head and neck cancer.

Carcinoma, Squamous Cell↗

[Annual chest X-ray in patients after treatment for laryngeal or oral cancer: only a limited number of second primary lung cancers detected].

OBJECTIVE: To evaluate the detection of second primary lung cancer in patients treated for laryngeal or oral cancer by means of the current annual chest radiography screening program. DESIGN: Retrospective follow-up. METHOD: In a source population of Utrecht University Hospital consisting of patients treated for laryngeal or oral cancer, the occurrence of non-simultaneous second primary lung cancer was analysed. The charts of the patients who developed second primary lung cancer were reviewed with respect to diagnosis (either by means of routine annual chest radiography or triggered by symptoms and signs) and treatment of lung cancer. A Kaplan-Meier survival analysis was performed for both routes of diagnosis and for each form of lung cancer treatment. RESULTS: The source population consisted of 2067 patients. Second primary lung cancer was diagnosed in 44 patients (37 with laryngeal and 7 with oral cancer). In 21 patients lung cancer was diagnosed by means of annual chest radiography (routine group). The remaining 23 patients presented with symptoms and signs (symptomatic group). In 13 patients, surgery with curative intent was performed. These patients had the best prognosis. Of the surgical cases, 12 out of 13 patients (27% of the total of 44) were in the routine group. Patients in the routine group had better survival than those in the symptomatic group. CONCLUSION: In view of the limited number of patients with second primary lung cancer and the small percentage of patients eligible for curative surgical treatment detected by annual radiography, screening in its present form is of little benefit.

Humans↗

Peutz-Jeghers syndrome: 78-year follow-up of the original family.

BACKGROUND: The association between heredity, gastrointestinal polyposis, and mucocutaneous pigmentation in Peutz-Jeghers syndrome (PJS) was first recognised in 1921 by Peutz in a Dutch family. This original family has now been followed-up for more than 78 years. We did mutation analysis in this family to test whether the recently identified LKB1 gene is indeed the PJS gene in this family. METHODS: The original family was retraced and the natural history of PJS was studied in six generations of this kindred by interview, physical examination, chart view, and histological review of tissue specimens. DNA-mutation analysis was done in all available descendants. FINDINGS: Clinical features in this family included gastrointestinal polyposis, mucocutaneous pigmentation, nasal polyposis, and rectal extrusion of polyps. Survival of affected family members was reduced by intestinal obstruction and by the development of malignant disease. A novel germline mutation in the LKB1 gene was found to cosegregate with the disease phenotype in the original family. The mutant LKB1 allele carried a T insertion at codon 66 in exon 1 resulting in frameshift and stop at codon 162 in exon 4. INTERPRETATION: The morbidity and mortality in this family suggest that PJS is not a benign disease. An inactivating germline mutation in the LKB1 gene is involved in the PJS phenotype in the original and oldest kindred known to be affected by PJS.

Adolescent↗

Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families.

The Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder in which gastrointestinal hamartomatous polyposis, mucocutaneous pigmentation, and a predisposition for developing cancer are transmitted in an autosomal dominant fashion. The recently identified LKB1/STK11 gene located at chromosome 19p13.3 is mutated in a number of PJS pedigrees. We performed mutation analysis in 19, predominantly Dutch, PJS families. In 12 of these families, we identified LKB1/STK11 mutations, none of which has been described before. These 12 novel LKB1/STK11 mutations consist of one nonsense mutation, three frameshift deletions, three frameshift insertions, two acceptor splice site mutations, and three missense mutations. In addition, we detected four polymorphisms in LKB1/STK11. In the remaining seven PJS families, we found no apparent abnormalities of the LKB1/STK1I gene, which could reflect the existence of locus heterogeneity in PJS. None of the mutations occurred in more than one family, and a number were demonstrated to have arisen de novo. The diverse array of mutations found, the apparent high mutation rate, as well as the existence of a possible second PJS locus, renders diagnostic or predictive genetic testing in individual patients difficult, although future identification of additional mutations or even gene(s) will help in increasing the yield of direct mutation analysis.

AMP-Activated Protein Kinase Kinases↗

Preradiation dental extraction decisions in patients with head and neck cancer.

OBJECTIVE: The first objectives of this international survey were to study how dental-related and radiotherapy-related risk factors influence clinicians' preradiation dental decision making in patients with head and neck cancer and to evaluate clinicians' degree of certainty in making such decisions. A further objective was to examine the correlation of clinicians' policies with a policy based on a model for dental decision support that was presented in an earlier article. STUDY DESIGN: A consensus questionnaire was mailed to 54 oral-maxillofacial surgeons and hospital-based dentists at a number of international locations. The responses were aggregated and anonymously analyzed through use of a multiple regression procedure. RESULTS: Forty-four clinicians returned the questionnaire (response rate, 81%). Nine clinicians (20%) were using printed clinical guidelines for preradiation dental screening. Eighty-eight percent of clinicians' preradiation decisions and 49% of their certainty could be explained by the studied risk factors. Not all risk factors were significant at P <.001. Clinicians' policies showed high correlation (.85) with the policy based on the model for dental decision support. CONCLUSIONS: The findings support our previous assumption that policies in this field seem to be based primarily on clinical experience and opinions rather than on evidence-based clinical guidelines. We conclude that the clinical usefulness and validity of the model for dental decision support should now be tested and that it could also serve as a training tool.

Australia↗

Treatment of central giant cell granuloma of the jaw with calcitonin.

Giant cell granuloma of the jaw is a benign lesion that may cause local destruction of bone and displacement of teeth. The common therapy is curettage or resection, which may be associated with loss of teeth and, in younger patients, loss of dental germs. An alternative treatment has recently been introduced, in which patients receive a daily dose of calcitonin. Four patients who have been treated with calcitonin in various concentrations for at least 1 year are reported. In all patients, complete remission of the giant cell granuloma was observed, without signs of recurrence. The working mechanism of calcitonin is discussed, as are length of treatment and optimal dose.

Adolescent↗

Sequencing analysis of RNA and DNA of exons 1 through 11 shows p53 gene alterations to be present in almost 100% of head and neck squamous cell cancers.

Data on p53 alterations in human cancers are mainly based on studies restricted to the core domain (exons 5-9), because mutations outside this region are assumed to be rare. To test this assumption, we studied 25 consecutive patients with primary, untreated head and neck squamous cell carcinoma (HNSCC) with a p53 mutation analysis strategy that consists of sequencing all 11 p53 exons and the complete p53 mRNA. With this method, we encountered p53 mutations in 91% of patients; 33% of these were located outside the core domain. Overexpression of the p53 protein was assessed with staining with antibody Bp 53-12-1. Protein overexpression was found in 64%. In one case, p53 overexpression occurred without p53 gene mutations. Analysis of tumor tissue from two autopsied patients with multiple lesions in the head and neck and at distant sites allowed analysis of the clonal relationship of the different tumor foci. In one patient, the head and neck lesion had a mutation different from the one observed at the distant sites, suggesting two different primary tumors, one of them leading to widespread metastastic disease. In all lesions from the second patient, the same mutation was found, suggesting one primary that had metastatized. It appears that sequencing of all exons of the p53 gene is vital for assessment of the real incidence of p53 mutations in HNSCC, because 33% of all mutations are located outside the core domain, leading to a mutation frequency of almost 100% in HNSCC. In 96% of cases, either presence or absence of p53 protein expression could be explained by the type of p53 gene mutation. When only analyzing the p53 core domain, the incidence of p53 mutations in HNSCC is underestimated.

Amino Acid Sequence↗

[Botulinum toxin type A treatment of cosmetically disturbing masseteric hypertrophy].

Two patients, a woman aged 21 and a man aged 29, with asymmetrical swellings of both mandibular angles and a painful, heavy sensation in the masticatory muscles (and in the woman also round the maxillary joint), were diagnosed as having hypertrophy of the masseter muscles. Both had the habit of jaw clenching and tooth grinding. Treatment consisted not of the traditional surgical debulking which also allows correction of overdeveloped osseous mandibular angles, but of injections with botulinum toxin type A. Injection of 40-60 IU (product: Botox) per muscle was followed by some atrophy; cosmetically satisfactory results were achieved after repetition of the treatment a few months later. Reduction of muscle volume was confirmed by a quantitative volumetric assessment of MRI scans. In the female patient, the pain also abated.

Adult↗

An image analysis study on nuclear morphology in metastasized and non-metastasized squamous cell carcinomas of the tongue.

In a retrospective case-control study on 46 metastasized and 34 non-metastasized primary tongue carcinomas, the nuclear morphology and chromatin pattern were assessed in 3 microns thick, formalin-fixed, paraffin-embedded, and Feulgen-stained tissue sections of surgical resection specimens, by means of high-resolution computer-assisted image analysis. The aim of this study was to disclose differences in karyometric features, such as nuclear size-, shape-, and chromatin-pattern features, between these groups, with a view to developing a discriminant function that can predict the occurrence of metastasis for the individual patient. In addition, the lymph node metastases of 31 patients and the normal tongue epithelium of 21 patients were also assessed, to study the possible differences between these two groups and primary tumours. In the metastasized tumours, the chromatin was significantly more condensed (P = 0.01) and exhibited significantly less variation in chromatin condensation (P < 0.001) than in the group of non-metastasized carcinomas. Comparison of lymph node metastases with their primary tumours disclosed only minor differences in chromatin pattern. These findings suggest that only minor genetic differences exist between primary tongue carcinomas and their metastases. Tumour cells of tongue carcinomas showed highly significant differences from cells of normal tongue mucosa for most karyometric features. Logistic regression analysis resulted in a classifier, based on the circularity of the nucleus (CIRC) and the standard deviation of the chromatin condensation (SD COND), to predict the occurrence of lymph node metastases. After cross-validation, the percentages of correct classifications in the group of metastasized and non-metastasized tumours were 72 and 62 per cent, respectively. These results are comparable to the classification results obtained from a classifier based on the clinical T-stage, but our karyometric classification results show a much more equal distribution between the sensitivity and specificity. Karyometric features appeared to be more appropriate to predict metastases than biomarkers such as p53, bcl-2, and Ki-67.

Carcinoma, Squamous Cell↗

Information on infraorbital nerve damage from multitesting of sensory function.

Sensory disturbance following orbitozygomatic complex fractures was studied in 65 patients from 4 treatment groups which represented potentially varying degrees of sensory disturbance. The fracture-type-dependent treatments were: no surgical intervention (n = 20), closed reduction with or without wire fixation (n = 17), open reduction with miniplate fixation (n = 15) and/or reconstruction of the orbital floor (n = 13). In order to assess the sensory function of different classes of afferent fibres, several methods of sensory testing were applied. On average 6.3 months after treatment, the patient's report was obtained, and tests regarding touch, two methods of two-point discrimination, and cold were applied on the cheek and upper lip. The degree of sensory disturbance was method-dependent. In patients who underwent closed reduction, pronounced levels of positive correlation occurred between results from different tests or from both test sites. The levels of these correlations were, in general, low for all other treatments. These findings suggest that afferent fibres of both large and small diameter tended to be permanently damaged in the patient group with closed reduction. In contrast, the types of sensory afferent fibres that were involved in the trauma and/or their recovery were highly variable within patients and sites for all other treatment groups.

Adolescent↗

Infraorbital nerve function following treatment of orbitozygomatic complex fractures. A multitest approach.

Sensory disturbance following orbitozygomatic complex fractures was studied in 65 patients in relation to type of fracture and method of treatment. The fracture-type-dependent treatments were: no surgical intervention (n = 20), closed reduction with or without wire fixation (n = 17), open reduction with miniplate fixation (n = 15) and/or reconstruction of the orbital floor (n = 13). Several methods were applied to assess sensory function, on average 6.3 months after treatment, i.e. the patient's report and tests regarding touch, two methods of two-point discrimination, and cold, all applied on the cheek and upper lip. The various examinations indicated that, on average, the long-term sensory disturbance was most pronounced and severe in patients who underwent closed reduction without miniplate fixation. As the sensory disturbance of patients with open reduction and miniplate fixation approached the base-line level of patients for whom surgical intervention was not indicated, open reduction with miniplate fixation can be recommended as treatment for frontozygomatic suture fractures. The degree of sensory disturbance of patients who underwent orbital floor reconstruction was intermediate compared to patients with closed and open reduction respectively.

Adolescent↗

Pretherapy dental decisions in patients with head and neck cancer. A proposed model for dental decision support.

OBJECTIVE: The proposed model was designed to function as a tool for the development and testing of evidence-based clinical guidelines for the pretherapy oral screening and dental management of patients with head and neck cancer. STUDY DESIGN: Methods of clinical decision analysis were used to analyze the decision dilemma and construct a decision algorithm and decision tree. The robustness of the model was tested by means of a probabilistic sensitivity analysis with second-order Monte Carlo simulations (n = 10.000). RESULTS: Clinical criteria for evaluating dental pathologic conditions and malignancy- and patient-related conditions were transformed in probability estimates. The tradeoffs between the benefits and drawbacks of the dental intervention were integrated into the model to identify the optimal option for dental intervention. The calculation process of "folding back and averaging out" the decision tree enabled the identification of the optimal options for dental intervention in four different pretherapy risk conditions. CONCLUSIONS: A priori testing of the proposed model with 95% confidence intervals suggests that it has a great potential for solving clinical dilemmas associated with pretherapy dental decision-making. In addition, it seems a useful tool for the development of evidence-based clinical guidelines. A posteriori clinical testing should further validate the model before its assimilation into clinical practice takes place.

Algorithms↗

[Calcitonin therapy in large or recurrent central giant cell granulomas of the lower jaw].

In three patients, boys aged 4 and 3 years and a woman aged 18 years, central giant cell granuloma of the mandible was diagnosed. As an alternative to mutilating surgery all three patients were treated with calcitonin, the second one when he was 16 years old and after the tumour had recurred 5 times following extirpation. After an average therapy of 14 months, no recurrences were encountered. Mean follow-up was 8 months. In local biopsies mature bone tissue was seen during the first 3 months of therapy, slight changes of the levels of procollagen peptide type 1, parathormone and hydroxyproline in 24-hour urine were noticed, all within the normal limits. During and after termination of therapy serum calcium, phosphate and parathormone stayed within the normal range. Side effects consisted of flushes, nausea and vomiting. Calcitonin is still an experimental therapy for central giant cell granuloma, but may be a good alternative to mutilating surgery in case of large or multiple recurring tumours.

Adolescent↗

Osteosarcoma of the jaw bones. Long-term follow up of 48 cases.

To evaluate the incidence and treatment results of osteosarcoma of the jaw (OSJ) in the Netherlands, data from 48 patients with a histologically proven diagnosis of osteogenic sarcoma of the maxilla or mandible were retrospectively analysed. Patient files, covering the period from 1964 to 1992, were obtained from all university hospitals in the Netherlands and the Netherlands Cancer Institute. The incidence of OSJ in the Netherlands is estimated to be at least 0.14 per 1,000,000. The overall 10-year survival was 59%. Distant metastasis occurred in 21% and local recurrences in 31% of the cases. Survival was significantly better in case of radical surgery and small tumours. Long-term survival after treatment of OSJ was good if complete surgical excision was achieved. Radiotherapy should only be considered to prevent local recurrence if surgery is not complete. The possible benefit of current chemotherapy in preventing metastatic disease is still questionable. Since other malignant neoplasms associated with OSJ occurred in 17% of the cases, lifelong follow up is mandatory for the detection of these second primary malignancies.

Adolescent↗

Osteochondroma of the mandibular condyle. A case report.

Osteochondroma of the mandibular condyle is extremely rare and may cause signs and symptoms like those seen in patients with temporomandibular joint dysfunction. Differentiation between osteochondroma and condylar hyperplasia is not possible on histologic grounds alone, but the radiographic and intraoperative findings together are usually sufficient to establish a definite diagnosis.

Adult↗

Polyactive as a bone-filler in a beagle dog model.

Calcification is a crucial step in the bone-bonding mechanism of PEO/PBT hydrogel copolymers (Polyactive, a new generation of bone-fillers. A beagle dog study was conducted to determine whether the preoperative presence of a calcium phosphate layer (precalcification) on a PEO/PBT 80/20 copolymer would further increase the bone-bonding rate. Standard bone cavities were filled with either precalcified or nonprecalcified porous cylindric PEO/PBT 80/20 implants, or hydroxyapatite granules held together with PEO/PBT 70/30, or were left unfilled. A significantly higher percentage of mineralized component was present in the cavities filled with the precalcified PEO/PBT 80/20 copolymer than in the control defects. As a result of swelling by fluid-uptake, the press-fit inserted copolymer implants showed a significant reduction in pore size, thus preventing optimal bone ingrowth. Both precalcification of the copolymer and underfilling of the defect, to create space for the copolymer to increase in diameter, stimulate postoperative calcification and bone ingrowth in PEO/PBT 80/20 copolymers.

Alveolectomy↗

Autopsy findings in patients with head and neck squamous cell cancer and their therapeutic relevance.

A series of 63 autopsied patients with a history of head and neck squamous cell cancer (HNSCC) is reported with emphasis on the importance of locoregional disease (LRD) versus distant metastasis (DM) in the terminal course of the disease. There were 49 males and 14 females; mean age 64.9 years (range 35-94 years). Locoregional disease was present in 39 patients (62%), in 25 (40%) without tumour at other body sites outside the head and neck region. Distant metastasis was observed in 15 patients (24%); in 12 (19%), it occurred with concomitant LRD. Second primary tumours (SPT) were observed in 20 patients (32%). They occurred in the head and neck region (n = 7; 11%), the lung (n = 9; 14%) and at miscellaneous other sites (n = 4; 6%). Of the 13 patients with SPT outside the head and neck region, 2 had concomitant LRD. 11 patients (17%) died due to other causes, no tumour being found at autopsy. These figures indicate that still a major part of HNSCC patients die with LRD as the single tumour manifestation, which means that improvement of local tumour control will result in a significant therapeutic gain.

Adult↗