Survival of non-Western first generations immigrants with stomach cancer in North East Netherlands.

BACKGROUND: Isolated groups, such as first generation non-Western immigrants, are at risk for suboptimal utilisation of the health care system resulting in a worse outcome. METHODS: From 1989 to 2007, all patients with stomach cancer were selected from the Comprehensive Cancer Centre North-East cancer registry. Associations between country of birth and patient, tumour and treatment characteristics were determined using χ(2) analysis. Relative survival analysis was used to estimate relative excess risk of dying according to country of birth (non-Western vs Western). RESULTS: After adjusting for confounding factors (patient, tumour and treatment related), the risk of dying was lower for first generation non-Western immigrants (relative excess risk 0.55, 95% confidence interval 0.43-0.70) compared with Western patients. CONCLUSION: Although the better survival of first generation non-Western immigrants with stomach cancer remains unexplained, it argues against accessibility problems within the Dutch health care system.

FDG-PET probe-guided surgery for recurrent retroperitoneal testicular tumor recurrences.

AIM: Tumor marker based recurrences of previously treated testicular cancer are generally detected with CT scan. They sometimes cannot be visualized with conventional morphologic imaging. FDG-PET has the ability to detect these recurrences. PET probe-guided surgery, may facilitate the extent of surgery and optimize the surgical resection. METHODS: Three patients with resectable 2nd or 3rd recurrent testicular cancer based on elevated tumor markers after previous various chemotherapy schedules and resections of residual retroperitoneal tumor masses were included in this study. A diagnostic FDG-PET was performed and a hotspot in previously operated area of the retroperitoneal space in all three patients was visualized. PET probe-guided surgery was performed using a high-energy gamma probe 3 h post-injection of 500 MBq FDG. RESULTS: All patients showed extended adhesions and scar tissue in the retroperitoneal area due to the previous surgeries. Pre-operative PET/CT scan showed a good correlation with intra-operative PET probe-guided detection of recurrent lesions. There was a high target to background ratio (TGB) of 5:1 during the procedure. In one patient, a 2 cm large lesion, which did not show on pre-operative FDG-PET scan, was detected with the PET probe. Histopathologic tissue evaluation demonstrated recurrent vital tumor in all PET probe positive lesions. CONCLUSIONS: PET probe-guided surgery seems to be a promising tool to localize FDG-PET positive lesion in recurrent testicular cancer in hardly accessible surgical locations. PET probe-guided surgery might be a useful technique in surgical oncology for recurrent testicular cancer and has the potential to be applied in surgery of other malignant diseases.

Effect of hospital characteristics on outcome of patients with gastric cancer: a population based study in North-East Netherlands.

BACKGROUND: Surgical resection is an important factor in the curative treatment of gastric cancer. However a variety of aspects of surgical treatment that potentially influence outcome are still not well defined. This study aims to assess the influence of hospital type, referral pattern and proximal or distal location of the tumour on the ultimate survival. METHODS: From January 1994 to January 2007, a total of 5245 patients were diagnosed with gastric adenocarcinoma in the region of the Comprehensive Cancer Centre North-East Netherlands. Hospitals in this region were categorized into three types: teaching university (TU), teaching non-university (TNU), and non-teaching hospitals (NT). The influence of hospital type, referral for surgery and location of the tumour on the relative survival of operated patients was studied. RESULTS: Of the 5245 patients, 2334 patients underwent surgery. For operated patients, the 5-year relative survival was 42.5% for the TU versus 34.0% and 35.5% for respectively TNU and NT hospitals (p = 0.064), with no difference (p = 0.38) in relative survival (25.6-31.9%) in the proximal tumours. A significant difference was found between the hospitals in the 5-year relative survival in the distal tumours; 59.7% in the TU versus 36.4% in the TNU and 36% in the NT (p = 0.03 univariate), however this was not confirmed in the multivariate analysis (p = 0.184). High referral centres did not perform better as far as survival is concerned than low referral hospitals. In conclusion the hospital type in our region did not significantly influence outcome of surgery for gastric cancer.

Skin capillary permeability in the diabetic foot with critical limb ischaemia: the effects of a phVEGF165 gene product.

AIMS: To measure capillary permeability, assessed by skin capillary sodium fluorescein (NaF) leakage, in patients with diabetes mellitus with critical limb ischaemia (DM-CLI) and to compare the effects of vascular endothelial growth factor (VEGF) with those of placebo. METHODS: NaF leakage was assessed in 17 patients with DM-CLI, in 24 diabetes mellitus (DM) patients without clinical signs of macrovascular disease or neuropathy (DM-C) and in 22 healthy control subjects. The 17 DM-CLI patients were randomized to receive phVEGF165 gene product (n = 11) or placebo (n = 6). Measurements were repeated after 28 days. RESULTS: DM-CLI patients had a longer dye arrival time (DAT), but NaF leakage was similar to control subjects, while capillary permeability was increased in DM-C compared with control subjects. Leakage curve rose in patients receiving VEGF and fell in those receiving placebo, 28 days after administration. The decrease in DAT in the VEGF group was not significant, whilst DAT rose in the placebo group. Perfusion pressures were similar in the two groups. CONCLUSION: No increase in capillary leakage in DM-CLI was found, probably because an increased capillary filtration coefficient is counterbalanced by a marked fall in perfusion pressures. Increased capillary leakage may be one explanation for oedema formation after VEGF treatment.

Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients.

Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related infections were seen in 28.3% of patients (11 infections per 1000 catheter-days). Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures (56%). No systemic fungal infections occurred. Cox regression analysis showed that duration of neutropenia >10 days (P=0.04), using the catheter for both stem-cell apheresis and high-dose chemotherapy (P= <0.01), and use of total parenteral nutrition (TPN, P=0.04) were predictive for catheter-related infections. In conclusion, a high incidence of catheter-related infections after high-dose chemotherapy was seen related to duration of neutropenia, use of the catheter for both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective use and choice of catheters could lead to a substantial reduction of catheter-related infectious complications.

Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial.

Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF165 (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n=27) treated with placebo versus phVEGF165-treated patients (n=27) the following results were found: 6 amputations versus 3 (p=not significant [NS]); hemodynamic improvement in 1 versus 7 (p=0.05); improvement in skin ulcers, 0 versus 7 (p=0.01); decrease in pain, 2 versus 5 (p=NS); and overall, 3 versus 14 responding patients (p=0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF165-containing plasmid. There were no substantial adverse events.

Randomised Phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer.

BACKGROUND: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer. PATIENTS AND METHODS: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-infusion, FA 200 mg/m(2), 1-h infusion. 5-FU 2600 mg/m(2), 24-h infusion day 1, q 2 wk. The primary endpoint was response rate (RR). RESULTS: The median follow-up is 31.8 months, 90.4% of the patients have died. Confirmed RR, progression free survival (PFS; months) and median overall survival (OS; months) in 5FU/LV versus 5FU/LV/oxaliplatin were respectively 18.5% versus (vs) 33.8% (P = 0.004), 5.6 vs 6.7 (P = 0.016) and 13.3 vs 13.8 (P = 0.619). In the 5FU/LV/oxaliplatin arm less grade (3/4) toxicity was measured for diarrhoea, stomatitis, an increase in idiosyncratic side effects and neurosensory events compared with 5FU/LV. The quality of life (QOL) was equal in both arms. Second line treatment was given in 62% of the patients, crossover of 5FU/LV to 5FU/LV/oxaliplatin occurred in 14%. CONCLUSIONS: Oxaliplatin in the first-line resulted in an increased RR and PFS with less grade 3/4 mucositis/diarrhoea compared with 5FU/LV alone. Idiosyncratic side effects deserve attention with oxaliplatin. Despite a low treatment cross over rate, OS in both groups was comparable.

Antagonism of HSV-tk transfection and ganciclovir treatment on chemotherapeutic drug sensitivity.

Our study focused on the influence of herpes simplex virus thymidine kinase (HSV-tk) expression and ganciclovir (GCV) treatment on the sensitivity of C6 glioma cells to frequently used chemotherapeutic drugs, i.e. adriamycin (ADR), cisplatin (CDDP), 5-fluorouracil (5-FU), and methotrexate (MTX). Transfection with HSV-tk revealed an increased sensitivity to GCV and CDDP and a decreased sensitivity to ADR and MTX. No significant differences were found in sensitivity to 5-FU. Combined treatment in a HSV-tk negative cell line revealed an additive effect when GCV was combined with ADR, whereas an antagonistic effect was found when GCV was combined with CDDP, 5-FU, or MTX. Comparable results were obtained in an HSV-tk positive cell line, apart from CDDP, which showed an additive effect. In conclusion, both HSV-tk transfection and subsequent GCV treatment can influence the sensitivity of tumor cells to various chemotherapeutic drugs in an antagonistic manner. Therefore, combining HSV-tk/GCV gene therapy with chemotherapy might not always be beneficial.

[New oncolytic agents and immunomodulators and their application]. / Nieuwe oncolytica en immunomodulantia en hun toepassing.

After a long period without change, colorectal oncology has in recent years entered the frontline of progress in cancer treatment and research. Improved diagnostic techniques have brought forward the diagnosis of metastatic disease, enabling potential curative surgery in the case of liver metastases. Due to both the earlier start of systemic treatment and the increase in number of active drugs, survival of patients with metastatic disease has increased to a median of approximately 18 months. Two important cytotoxic drugs, oxaliplatin and irinotecan, have contributed to this progress. Recently, it was demonstrated that addition ofa monoclonal antibody against vascular endothelial growth factor, bevacizumab, led to an increase in survival comparable to the effects of both cytotoxic agents. Increase in survival, as a hallmark for drug efficacy, is an endpoint that patients and the medical community seem to agree on. The financial consequences of these combinations for the hospital budget are considerable, but their share in the total drug economy is still small. Oxaliplatin has also emerged as a useful drug in the adjuvant setting, after surgery for primary colon cancer.

Relevance of high-dose chemotherapy in solid tumours.

Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.

Closed system generation of dendritic cells from a single blood volume for clinical application in immunotherapy.

Dendritic cells (DC) used for clinical trials should be processed on a large scale conforming to current good manufacturing practice (cGMP) guidelines. The aim of this study was to develop a protocol for clinical grade generation of immature DC in a closed-system. Aphereses were performed with the Cobe Spectra continuous flow cell separator and material was derived from one volume of blood processed. Optimisation of a 3-phase collection autoPBSC technique significantly improved the quality of the initial mononuclear cell (MNC) product. Monocytes were then enriched from MNC by immunomagnetic depletion of CD19+ B cells and CD2+ T cells and partial depletion of NK cells using the Isolex 300I Magnetic cell selector. The quality of the initial mononuclear cell product was found to determine the outcome of monocyte enrichment. Enriched monocytes were cultured in Opticyte gas-permeable containers using CellGro serum-free medium supplemented with GM-CSF and IL-4 to generate immature DC. A seeding concentration of 1 x 10(6) was found optimal in terms of DC phenotype expression, monocyte percentage in culture, and cell viability. The differentiation pattern favours day 7 for harvest of immature DC. DC recovery, viability, as well as phenotype expression after cryopreservation of immature DC was considered in this study. DC were induced to maturation and evaluated in FACS analysis for phenotype expression and proliferation assays. Mature DC were able to generate an allogeneic T-cell response as well as an anti-CMV response as detected by proliferation assays. These data indicate that the described large-scale GMP-compatible system results in the generation of stable DC derived from one volume of blood processed, which are qualitatively and quantitatively sufficient for clinical application in immunotherapeutic protocols.

[18F]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis.

Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial. Subtle brain infections with HSV may be causally related to neuropsychiatric disorders such as Alzheimer's dementia. We investigated the feasibility of a noninvasive positron emission tomography (PET) imaging technique using [(18)F]FHPG as a tracer for the detection of HSE. For this purpose, rats received HSV-1 (infected group) or phosphate-buffered saline (control group) by intranasal application, and dynamic PET scans were acquired. In addition, the distribution of tracer accumulation in specific brain areas was studied with phosphor storage imaging. The PET images revealed that the overall brain uptake of [(18)F]FHPG was significantly higher for the infected group than for control animals. Phosphor storage images showed an enhanced accumulation of [(18)F]FHPG in regions known to be affected after intranasal infection with HSV. High-performance liquid chromatography metabolite analysis showed phosphorylated metabolites of [(18)F]FHPG in infected brains, proving that the increased [(18)F]FHPG uptake in infected brains was due to HSV thymidine kinase-mediated trapping. Freeze lesion experiments showed that damage to the blood-brain barrier could in principle induce elevated [(18)F]FHPG uptake, but this nonspecific tracer uptake could easily be discriminated from HSE-derived uptake by differences in the tracer kinetics. Our results show that [(18)F]FHPG PET is a promising tool for the detection of HSV encephalitis.

Monitoring HSVtk suicide gene therapy: the role of [(18)F]FHPG membrane transport.

Favourable pharmacokinetics of the prodrug are essential for successful HSVtk/ganciclovir (GCV) suicide gene therapy. [(18)F]FHPG PET might be a suitable technique to assess the pharmacokinetics of the prodrug GCV noninvasively, provided that [(18)F]FHPG mimics the behaviour of GCV. Since membrane transport is an important aspect of the pharmacokinetics of the prodrug, we investigated the cellular uptake mechanism of [(18)F]FHPG in an HSVtk expressing C6 rat glioma cell line and in tumour-bearing rats. The nucleoside transport inhibitors dipyridamol, NBMPR and 2-chloroadenosine did not significantly affect the [(18)F]FHPG uptake in vitro. Thymidine and uridine significantly decreased [(18)F]FHPG uptake by 84 and 58%, respectively, but an enzyme assay revealed that this decline was due to inhibition of the HSVtk enzyme rather than membrane transport. Nucleobase transport inhibitors, thymine and adenine, caused a 58 and 55% decline in tracer uptake, respectively. In vivo, the ratio of [(18)F]FHPG uptake in C6tk and C6 tumours decreased from 3.0+/-0.5 to 1.0+/-0.2 after infusion of adenine. Thus, in our tumour model, [(18)F]FHPG transport exclusively occurred via purine nucleobase transport. In this respect, FHPG does not resemble GCV, which is predominantly taken up via the nucleoside transporter, but rather acyclovir, which is also taken up via the purine nucleobase carrier.

Developments in treatment of primary irresectable rectal cancer.

Abstract The treatment options for primary irresectable rectal cancers are discussed. Assessment of tumour stage is the first step for an appropriate choice of treatment. Following a diagnosis of rectal cancer, a vast array of diagnostic procedures is available to determine its stage, and thereby its best treatment options. From the many (new) diagnostic options the merits and drawbacks are discussed. If a diagnosis of irresectability is made, further treatment options should include radiotherapy in most cases, some aspects of timing and application, i.e. intra-operative treatment are discussed. Chemotherapy options are manifold, the results are discussed and some new options are explored.

Treatment of locally recurrent rectal cancer, results and prognostic factors.

PURPOSE: Assessment of the results and prognostic factors in patients with locally recurrent rectal cancer treated with curative intent. PATIENTS AND METHODS: Forty patients with an isolated pelvic recurrence of rectal cancer were studied retrospectively. The treatment consisted of radiotherapy alone or combined with chemotherapy and/or surgery performed between January 1992 and July 2001. Radiotherapy was given with a 3-4 fields technique (6-15 MV), five times a week. The median radiation dose was 50 Gy (range 25-66.6 Gy). Twenty-five patients underwent salvage surgery. Five patients were treated with concomitant chemotherapy (5-fluoro-uracil/leucovorin) (5FU/LV) during the 1st and 5th week of radiotherapy. RESULTS: Twenty-two of the 40 patients were male. The local recurrence free survival after 3 and 5 years, respectively, was 49 and 39%. Male gender was the only independent factor associated with failure of local control. The 3 and 5-year overall survival of the total group was 36 and 19%, respectively, with a median survival of 26 months. CONCLUSION: In a selection of patients in the treatment of locally recurrent rectal cancer valuable local palliation if not cure, can be reached. A multimodality approach seems to offer the best chances in this threatening situation.

The happy destiny of frozen haematopoietic stem cells: from immature stem cells to mature applications.

Forty years ago, van Putten described in the European Journal of Cancer (see this issue) quantitative studies on the optimal storage techniques of mouse and monkey bone marrow suspensions. Survival of the animals after irradiation following injection with stored bone marrow cell suspensions was the endpoint. He observed some species differences, but based on the data obtained considered a careful trial of the glycerol-polyvinylpyrrolide (PVP) combination for storage of marrow in man was indicated. In spite of this, dimethyl sulphoxide has become the 'standard' cryopreservant for human marrow stem cells. Over the last 40 years, there has been a tremendous increase in knowledge about haematopoietic stem cells and their use in the clinic. Haematopoietic stem cells are now known to travel between the bone marrow and peripheral blood and are the best-characterised adult stem cells. These cells are currently widely used for transplantations in the clinic and are obtained from a wide variety of sources. These include the bone marrow, peripheral blood, cord blood, autologous as well as allogeneic stem cells from related or unrelated donors. Increasingly, data has become available that adult haematopoietic stem cells can generate differentiated cells belonging to other cell types, a process called "developmental plasticity". Thus, they may contribute to non-haematopoietic tissue repair in multiple organ systems. This has created a whole new potential therapeutic armamentarium for the application of haematopoietic stem cells outside of the area of malignancies and haematopoietic disorders.

5FU and oxaliplatin-containing chemotherapy in two dihydropyrimidine dehydrogenase-deficient patients.

Patients with a germline mutation leading to a deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme are at risk from developing severe toxicity on the administration of 5FU-containing chemotherapy. We report on the implications of this inborn genetic error in two patients who received 5FU and oxaliplatin. A possible co-medication effect of oxaliplatin is considered, as are the consequences of screening for DPD deficiency.

Factors influencing haematological recovery following high-dose chemotherapy and peripheral stem-cell transplantation for haematological malignancies; 1-year analysis.

Peripheral blood counts and factors influencing haematological recovery in 98 patients with a relapse-free survival of > or =1 year treated with high-dose chemotherapy (HDC) and peripheral stem-cell transplantation (PSCT) for haematological malignancies were analysed. One year after PSCT full haematological recovery was demonstrated for haemoglobin (Hb) in 47% of patients, for the white blood cell count (WBC) in 94%, and for platelets in 64%; 39% had a trilineage recovery. In the multivariate analysis, recovery was influenced by age (P=0.002), number of reinfused CD34+ cells (P=0.016), Hb at start of HDC (P=0.001), and platelets at start of HDC (P=0.008). One year following PSCT, 61% of patients still have subnormal values in one or more haematopoietic cell lineage, suggesting a limited bone-marrow reserve. Long-term recovery is highly dependent on age, blood counts at start of HDC and number of reinfused CD34+ cells without a threshold, all reflecting the residual function of bone marrow before HDC. Reinfusing more CD34+ cells can accelerate long-term haematological recovery.

Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study.

PURPOSE: To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically proven NSCLC, performance score <2, weight loss <10%, and normal organ functions were randomized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone (both 60 Gy). Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria (NCI CTC) and the Radiation Therapy Oncology Group (RTOG) criteria. Quality of life was measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/LC13 questionnaires. RESULTS: One-hundred and sixty patients were included. Pathologically confirmed persistent tumor was present in 53% of patients in the combination arm versus 58% in the radiotherapy alone arm (P=0.5). Median survival in the combination arm was 11.8 [95% confidence interval (CI) 9.3-14.2] months and in the radiotherapy alone arm 11.7 (95% CI 8.1-15.5) months; progression-free survival was not different between arms [6.8 and 7.5 months, respectively (P=0.28)]. Acute toxicity was mild, late toxicity was radiation-induced cardiomyopathy (three patients) and pulmonary fibrosis (five patients). Quality of life was not different between arms, but in all measured patients cough and dyspnea improved, pain became less, and slight paresthesia developed 3 months after treatment. CONCLUSION: Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival.

Screening for infectious foci in breast cancer patients prior to high-dose chemotherapy and stem cell transplantation.

UNLABELLED: Cancer patients treated with high-dose chemotherapy (HDC) followed by peripheral stem cell transplantation are at risk for infections during neutropenia. Our standard policy was to screen for potential infectious foci prior to HDC. Screening for infectious foci consisted of chest and sinus roentgenograms and a visit to the ear-nose-throat surgeon (ENT surgeon) and the dentist. The purpose of this study was to evaluate this approach. Between 1993 and 2000, 73 breast cancer patients received HDC. RESULTS: All chest roentgenograms were normal. ENT screening yielded in three (symptomatic) patients a potential infectious focus. In 32 patients (44%) a potential dental infectious focus was diagnosed and treated. During neutropenia after HDC clinical infections occurred in 15 patients (21%). In only 5 patients (7%) the infection focus was probably the upper respiratory tract. CONCLUSION: Potential ENT infectious foci were infrequent and all were symptomatic. Potential dental infectious foci were seen quite often; whether they would have had clinical impact if left untreated remains speculative.