Gert Jan Hordijk

Treatment failure and margin status in head and neck cancer. A critical view on the potential value of molecular pathology

Molecular pathology may demonstrate tumour cells not detected by histology. The idea has emerged that these cells influence the prognosis negatively and that their detection will lead to more appropriate treatment and improved patient survival. We theorized that tumour cells at surgical margins overlooked by the pathologist should demonstrate their clinical significance by causing recurrences at the primary site in the patients reported to have tumour-free margins by histology. To assess this assumption, we investigated the prognostic influence of the histologically determined status of the surgical margins. The material that formed the basis of this study consisted of 394 patients that underwent resection for their primary tumour during the years 1990-1995. In 207 patients, initial treatment was complete as assessed by conventional histopathological examination of the surgical specimen. In 187 patients, initial treatment was incomplete, defined as tumour in or close to the margin, or mild, moderate or severe dysplasia or in situ cancer at the margin. Causes for treatment failure were recorded for both groups separately. In the group with tumour-free margins, 16.9% had a second primary head and neck cancer, 8.2% had a second tumour in the lung, 10.6% had recurrent disease in the neck, 2.9% had distant metastasis, and 3.9% had local recurrence at the same site as the primary cancer. For the group without tumour-free margins, these figures were the following: second primary in the head and neck area: 17.1%, second primary in the lung: 7.0%, recurrent disease in the neck: 11.8%, distant metastasis: 8.0% and local recurrence at the primary site: 21.9%. Local recurrences were rare in patients in which the pathologist reported the resection to be complete. Although there may be tumour cells in surgical margins that evade histological detection, their clinical impact appears to be almost negligible.

Current indications for (adeno)tonsillectomy in children: a survey in The Netherlands.

OBJECTIVEnDespite the fact that (adeno)tonsillectomy is one of the procedures most frequently performed on children, studies of current indications are scarce. The purpose of this study is to determine the indications for (adeno)tonsillectomy in children younger than 15 years of age according to Dutch ENT surgeons and general practitioners (GPs).nnnMETHODSnDuring a period of 8 months, 18 ENT surgeons in seven ENT practices and 210 referring GPs filled out standard questionnaires for 349 children listed for tonsil surgery.nnnRESULTSnApart from recurrent tonsillitis (ENT: 40%, GP: 35%), findings such as enlarged tonsils (ENT: 42%, GP: 24%) and tonsillar crypt debris (ENT: 29%, GP: 17%) and non-specific symptoms such as listlessness (ENT: 28%, GP: 19%) and poor appetite (ENT: 28%, GP: 16%) were considered important criteria for surgery. Symptoms of obstructive sleep apnea were present in 25% (ENT) and 6% (GP) of patients but were considered indicative for surgery in only 11% (ENT) and 4% (GP). In contrast to ENT surgeons, GPs considered otitis media and hearing loss relatively important for (adeno)tonsillectomy.nnnCONCLUSIONSnApart from the generally accepted indications such as recurrent tonsillitis and obstructive sleep apnea, other indications play an equally important role in the decision to perform tonsil surgery in The Netherlands.

Nasal discharge and obstruction as presenting symptoms of Wegener's granulomatosis in childhood

A case with nasal manifestations as presenting symptoms of Wegeners granulomatosis in childhood is discussed. The diagnostic and treatment modalities are reviewed with emphasis on the specific problems concerning the side effects of treatment on the child.

Clinical relevance of protein-tyrosine (de-)phosphorylation in head and neck cancer

Previous studies have shown that protein tyrosine (de)phosphorylation plays an important role in head and neck cancer. Protein‐tyrosine kinases (PTK) and protein‐tyrosine phosphatases (PTPase) activities in the cytosol of tumor tissue were significantly increased compared to normal tissue of cancer patients as well as controls. Additionally, the enzyme activities in normal tissue of tumor patients were significantly higher than enzyme activities in normal tissue of the control group. In this paper, we have correlated the cytosolic and membranous PTK and PTPase activity of tumor and nontumor tissue with several clinical and histological parameters known to influence the clinical outcome. Furthermore, we have analyzed the value of the enzyme activities as an independent predictor of clinical behavior and occurrence of second primary tumors. We confirmed our earlier observations that cytosolic and membranous PTK activities and cytosolic PTPase activities in tumor tissues are increased compared to activities in nontumor tissues and controls. Moreover, we also confirmed the findings of increased enzyme activities in nontumor tissues compared to findings in control tissues. This finding in histologically proven healthy mucosa is highly interesting because it indicates that these biochemical changes are obviously not (yet) translated into morphological changes. Significant differences were found in membranous PTK activity when the patients were grouped by sex, tumor localization, lymph node metastasis, and previous radiotherapy. During the follow‐up period, no relation could be found between enzyme activities in tumor and/or nontumor tissues and disease‐free interval or occurrence of second primary tumors.

Moderators of the response to a nurse-led psychosocial intervention to reduce depressive symptoms in head and neck cancer patients

PurposeLittle is known about the variables that moderate the response to psychosocial interventions to decrease depressive symptoms in cancer patients. The purpose of this study was to determine whether variables associated with depressive symptoms in cancer patients in general moderate the response to a nurse-led psychosocial intervention in patients with head and neck cancer.MethodsThis study is a secondary analysis of a randomized controlled trial evaluating the effect of the nurse counseling and after intervention (NUCAI) on depressive symptoms 12xa0months after cancer treatment in patients with head and neck cancer. Of 205 patients, 103 received the NUCAI and 102 care as usual. Twenty-one variables were selected for analysis and a linear regression analyses including interaction terms was performed for each variable separately. Significant moderators were post hoc probed.ResultsFour moderators were found: marital status, global quality of life, emotional functioning, and social functioning. Patients who were married/living together or had low scores for global quality of life, and emotional or social functioning at baseline benefited more from the NUCAI than patients who were single or with high scores for global quality of life and emotional or social functioning.ConclusionsMarital status, global quality of life, and emotional and social functioning of head and neck cancer patients should be evaluated to determine whether they might benefit from a psychosocial intervention to combat depressive symptoms. Further research is necessary to replicate results and to contribute to the knowledge needed to make screening and personalized patient care possible.

25 Keel-, neus- en oorheelkunde

Samenvatting Bovensteluchtweginfecties, recidiverende middenoorontstekingen en tonsillitiden behoren tot de meest frequent voorkomende ziektebeelden bij kinderen. Mede door het veranderde beloop, de verminderde morbiditeit en vernieuwde inzichten zijn de behandelstrategieën de afgelopen jaren veranderd. Een afwachtend beleid, watchful waiting, lijkt nu veelal aangewezen.

DNA ploidy of primary and recurrent irradiated laryngeal tumors

Purpose: Radiosensitivity of diploid laryngeal cancers, as compared with that of aneuploid ones, appears to be increased. However, non conclusive data exist. If a causal relationship exists, then recurrent laryngeal cancer after irradiation should predominantly be characterized by aneuploidy.nn Patients and Methods: To test this hypothesis we compared ploidy of 24 primarily irradiated laryngeal cancers and their subsequent recurrences. T and N stages were assessed in accordance with the TNM classification system of the UICC. With flow cytometry DNA ploidy was assessed.nn Results: 1. Ploidy of 16 locally recurrent tumors did not differ from those of primary tumors, i. e. ten and six recurrences of diploid and aneuploid primary tumors, respectively, remained unchanged, 2. recurrences of four aneuploid primary tumors showed diploidy, 3. recurrences of four diploid primary tumors showed aneuploidy.nn Conclusions: The results of our study do not support the hypothesis that recurrent laryngeal cancer after irradiation of the primary tumor is characterized by aneuploidy.Ziel: Die Radiosensibilität diploider Larynxkarzinomzellen scheint höher zu sein als in aneuploiden Zellen. Es gibt dazu jedoch keine gesicherten Daten. Falls eine Kausalität besteht, sollten Larynxkarzinomrezidive nach Radiotherapie vorwiegend aneuploide Zellen aufweisen.nn Material und Methodik: Um diese Hypothese zu prüfen, wurde die DNA-Ploidie von 24 primär bestrahlten Larynxkarzinomen mit dem ihrer Rezidive verglichen. Die T- und N-Stadien der Malignome wurden nach dem TNM-Klassifikationssystem der UICC ermittelt. Der DNA-Gehalt wurde durchflusszytometrisch bestimmt.nn Ergebnisse: 1. Die DNA-Ploidie von 16 Lokalrezidiven unterschied sich nicht von der der Primärtumoren, d. h., zehn bzw. sechs Rezidive diploider und aneuploider Primärtumoren waren unverändert. 2. Die Rezidive von vier aneuploiden Primärtumoren waren diploid. 3. Die Rezidive von vier diploiden Primärtumoren waren aneuploid.nn Schlussfolgerung: Die Ergebnisse unserer Untersuchung sprechen gegen die Hypothese, dass für Larynxkarzinomrezidive nach Bestrahlung der Primärtumoren Aneuploide charakteristisch ist.