Use of Diffusion-Weighted Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Combined With Computed Tomography in the Response Assessment for (Chemo)radiotherapy in Head and Neck Squamous Cell Carcinoma.

AIMS: Our purpose was to assess the diagnostic accuracy and prognostic value of diffusion-weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) carried out 3-6 months after (chemo)radiotherapy in head and neck squamous cell carcinoma. MATERIALS AND METHODS: For this retrospective cohort study we included 82 patients with advanced-stage head and neck squamous cell carcinoma treated between 2012 and 2015. Primary tumours and lymph nodes were assessed separately. DWI was analysed qualitatively and quantitatively. 18F-FDG-PET/CT was evaluated using the Hopkins criteria. Dichotomous qualitative analysis was carried out for both modalities. Cox regression analysis was used for univariate analysis of recurrence-free survival (RFS). Significant univariate parameters were included in multivariate analysis. RESULTS: In 12 patients, locoregional recurrence occurred. With all imaging strategies, either single-modality or multi-modality, a high negative predictive value (NPV) was achieved (94.3-100%). In response evaluation of the primary site, the preferred strategy is 18F-FDG-PET/CT only, which resulted in a sensitivity of 85.7%, specificity of 86.5%, positive predictive value (PPV) of 37.5% and NPV of 98.5%. For response evaluation of the neck, the best results were obtained with a sequential approach only including the second modality in positive reads of the first modality. It did not matter which modality was assessed first. This strategy for lymph node assessment resulted in a sensitivity, specificity, PPV and NPV of 83.3%, 95.6%, 62.5%, and 98.5%, respectively. After correction for received treatment and human papillomavirus status, primary tumour (P = 0.009) or lymph node (P < 0.001) Hopkins score ≥4 on 18F-FDG-PET/CT remained significant predictors of RFS. CONCLUSION: For response evaluation of the primary tumour 18F-FDG-PET/CT only is the preferred strategy, whereas for the neck a sequential approach including both DWI and 18F-FDG-PET/CT resulted in the best diagnostic accuracy for follow-up after (chemo)radiotherapy. Qualitative analysis of 18F-FDG-PET/CT is a stronger predictor of RFS than DWI analysis.

The multilayered structure of the human corpus spongiosum.

PURPOSE: Urethral reconstruction is performed in patients with urethral strictures or for correction of congenital disorders. In the case of shortage of tissue, engineered tissue may enhance urethral reconstruction. As the corpus spongiosum (CS) is important in supporting the function of the urethra, tissue engineering of the urethra should be combined with reconstruction of a CS. For that purpose, detailed knowledge of the composition of the CS, more specifically its extracellular matrix (ECM) and vascularization is needed for scaffold design. The objective of this study is to analyze the microarchitecture of the CS through (immuno) histology and scanning electron microscopy (SEM). METHODS: The CS including the urethra of patients undergoing male-to-female genital confirming surgery was harvested. This CS was fixed and processed for either (immuno) histology or for SEM. RESULTS: Four layers could be distinguished in the CS; first a transition zone from urethra epithelium to a collagen rich layer, which was highly vascularized, followed by a second, elastin rich layer. The third layer was formed by veins, arteries and vascular spaces and the last layer showed the transition from this vascular rich region to the collagen rich tunica albuginea. In this layer collagen bundles intertwined with elastic fibres. In the CS different components of the ECM were visible and distinguishable. CONCLUSION: This study provides novel and detailed information on the microarchitecture of the CS and the distribution of vascularization, which is important for scaffold design in tissue engineering.

3D Orbital Reconstruction in a Patient with Microphthalmos and a Large Orbital Cyst-A Case Report.

BACKGROUND: Orbital cysts are rare developmental anomalies that can occur in microphthalmic and anophthalmic patients. Such cysts can promote orbital growth and subsequently markedly increase the size of the orbit, which is commonly underdeveloped in these patients. Cyst removal is therefore generally dissuaded (at least) in the first 5 years. CLINICAL CASE: A 6-year-old boy with a microphthalmos and a cyst developed protrusion of his prosthetic eye and a swelling of the lower eyelid. MRI showed a large cyst causing distortion of the right orbit. Due to the expansive orbital growth and subsequent misfitting of the prosthesis, cystectomy and orbital floor reconstruction was performed using 3D technology. CONCLUSION: 3D imaging and printing enables exact delineation of orbital cysts and the adjacent bony structures. Furthermore it offers the possibility to plan an individual surgical approach and to design and fabricate a custom fit orbital floor implant.

Quantitative diffusion-weighted MRI parameters and human papillomavirus status in oropharyngeal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus-negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC may also provide prognostic information. We explored whether human papillomavirus status and ADC values are independent tumor characteristics. MATERIALS AND METHODS: Forty-four patients with oropharyngeal squamous cell carcinomas underwent pretreatment DWI. ADC values for the primary tumors were determined by using 3 b-values in an ROI containing the largest area of solid tumor on a single section of an axial DWI image. Human papillomavirus status was determined with p16 immunostaining, followed by high-risk human papillomavirus DNA detection on the p16-positive cases. RESULTS: Twenty-two patients were human papillomavirus-positive (50.0%). ADC values were not significantly different between human papillomavirus-negative (ADC(mean) = 1.56 [1.18-2.18] × 10(3) mm(2)/s) and human papillomavirus-positive tumors (ADC(mean) = 1.46 [1.07-2.16] × 10(3) mm(2)/s). CONCLUSIONS: No significant association between ADC and human papillomavirus status was found in oropharyngeal squamous cell carcinomas. In our study population, differences in genetic and histologic features between human papillomavirus-positive and human papillomavirus-negative oropharyngeal squamous cell carcinomas did not translate into different ADC values. Long-term follow-up studies are needed to establish whether ADC has prognostic value and whether this is independent of the human papillomavirus status.

Diffusion-weighted imaging of the head and neck in healthy subjects: reproducibility of ADC values in different MRI systems and repeat sessions.

BACKGROUND AND PURPOSE: DWI is typically performed with EPI sequences in single-center studies. The purpose of this study was to determine the reproducibility of ADC values in the head and neck region in healthy subjects. In addition, the reproducibility of ADC values in different tissues was assessed to identify the most suitable reference tissue. MATERIALS AND METHODS: We prospectively studied 7 healthy subjects, with EPI and TSE sequences, on 5 MR imaging systems at 3 time points in 2 institutions. ADC maps of EPI (with 2 b-values and 6 b-values) and TSE sequences were compared. Mean ADC values for different tissues (submandibular gland, sternocleidomastoid muscle, spinal cord, subdigastric lymph node, and tonsil) were used to evaluate intra- and intersubject, intersystem, and intersequence variability by using a linear mixed model. RESULTS: On 97% of images, a region of interest could be placed on the spinal cord, compared with 87% in the tonsil. ADC values derived from EPI-DWI with 2 b-values and calculated EPI-DWI with 2 b-values extracted from EPI-DWI with 6 b-values did not differ significantly. The standard error of ADC measurement was the smallest for the tonsil and spinal cord (standard error of measurement = 151.2 × 10(-6) mm/s(2) and 190.1 × 10(-6) mm/s(2), respectively). The intersystem difference for mean ADC values and the influence of the MR imaging system on ADC values among the subjects were statistically significant (P < .001). The mean difference among examinations was negligible (ie, <10 × 10(-6) mm/s(2)). CONCLUSIONS: In this study, the spinal cord was the most appropriate reference tissue and EPI-DWI with 6 b-values was the most reproducible sequence. ADC values were more precise if subjects were measured on the same MR imaging system and with the same sequence. ADC values differed significantly between MR imaging systems and sequences.

Detection of calcifications in retinoblastoma using gradient-echo MR imaging sequences: comparative study between in vivo MR imaging and ex vivo high-resolution CT.

BACKGROUND AND PURPOSE: Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is considered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard. MATERIALS AND METHODS: Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1-71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated. RESULTS: All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor. Areas of nodular signal-intensity voids correlated with calcifications in 92% (24/26), and linear signal-intensity voids correlated with hemorrhage in 67% (6/9) of cases. The correlation of signal-intensity voids on SWI was better in 4 of 5 tumors compared with T2*WI. CONCLUSIONS: Signal-intensity voids on in vivo T2*WI correlate well with calcifications on ex vivo high-resolution CT in retinoblastoma. Gradient-echo sequences may be helpful in the differential diagnosis of retinoblastoma. The combination of funduscopy, sonography, and high-resolution MR imaging with gradient-echo sequences should become the standard diagnostic approach for retinoblastoma.

Recurrent Optic Perineuritis after Intranasal Cocaine Abuse.

Recurrent optic perineuritis can be related to orbital inflammation. Here we present the case of a 46-year-old male patient in whom recurrent episodes of optic perineuritis were related to chronic osteolytic sinusitis following intranasal cocaine abuse. Magnetic resonance imaging (MRI) demonstrated optic perineuritis adjacent to a soft tissue mass that intruded the orbit from the nasal cavity. Computed tomography (CT) confirmed destruction of the medial orbital wall. Staphylococcus aureus was cultured and biopsy showed granulomatous tissue. Visual outcome was poor. We review the literature and discuss the diagnostic pitfalls and management implications in relation to optic (peri)neuritis originating from the nasal sinuses.

Nutritional support in patients with GVHD of the digestive tract: state of the art.

An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD-DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B12 and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies.

Retinoblastoma: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis.

BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ(5min) and κ(17min), respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1. RESULTS: The median value of κ(5min) was 1.28 (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median value of κ(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ(5min) and 0.91 for κ(17min). CONCLUSIONS: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

Single-shot turbo spin-echo diffusion-weighted imaging for retinoblastoma: initial experience.

BACKGROUND AND PURPOSE: Retinoblastoma may exhibit variable hyperintensities on DWI, resulting in different values in the ADC maps, depending on their histology and cellularity. However, EP-based DWI has susceptibility artifacts and image distortions, which make DWI of the orbit a challenging technique. The aim of this study was to investigate the feasibility of single-shot turbo spin-echo (HASTE) DWI in the evaluation of children with retinoblastoma and to assess the value of ADC maps in differentiating viable and necrotic tumor tissue. MATERIALS AND METHODS: Two radiologists assessed conventional MR images, DWI, and ADC maps of 17 patients with retinoblastoma (n = 17 eyes). Non-EP DWI was performed by using a HASTE sequence with b-values of 0 and 1000 s/mm(2). ADC values were measured for enhancing and nonenhancing tumor tissue. ADC maps were compared with histopathologic findings regarding tumor differentiation and viability. RESULTS: On DWI, vital tumor tissue showed hyperintensity with negligible intensity of surrounding vitreous. The difference in mean (range) ADC values between enhancing (1.03 [0.72-1.22] × 10(-3) mm(2) s(-1)) and nonenhancing (1.47 [0.99-1.80] × 10(-3) mm(2) s(-1)) parts of retinoblastoma was statistically significant (P < .0005). Nonenhancing tumor parts showed a significantly lower ADC compared with vitreous (2.67 [2.24-3.20]×10(-3) mm(2) s(-1)) (P < .0005) and subretinal fluid (2.20 [1.76-2.96] × 10(-3) mm(2) s(-1)) (P < .0005). Histopathologically, low ADC values (enhancing tumor part) correlated to viable tumor tissue, whereas intermediate ADC values (nonenhancing tumor parts) correlated to necrotic tumor tissue. CONCLUSIONS: HASTE DWI allowed adequate characterization of retinoblastoma, and ADC is a helpful tool to differentiate viable and necrotic tumor tissue and might be valuable in monitoring the response to eye-preserving therapies.

Results of surgery for perforated gastroduodenal ulcers in a Dutch population.

OBJECTIVE: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment. PATIENTS AND METHODS: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality. RESULTS: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class. CONCLUSIONS: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment.

Intra-operative parathyroid hormone measurements - experience of a non-academic hospital.

BACKGROUND: Surgery is the treatment of choice for symptomatic primary hyperparathyroidism. The majority of research concerning intra-operative parathyroid hormone (ioPTH) measurements is conducted in university hospitals. Whether ioPTH measurements are feasible and useful in predicting the presence of remaining hyperfunctioning parathyroid tissue in a non-academic hospital remains uncertain. METHODS: Data were collected on all patients with biochemically proven and surgically treated primary hyperparathyroidism treated at the Reinier de Graaf Hospital from August 2002 to December 2007. RESULTS: Sixty-five patients were included. The mean pre-operative serum calcium level was 2.78 mmol/l (range 2.28 - 3.80 mmol/l, normal range 2.20 - 2.65 mmol/l) and the mean serum parathyroid hormone level 17.0 pmol/l (range 4.0 - 90.3 pmol/l, normal range 1.0 - 5.5 pmol/l). All patients were operated on for primary hyperparathyroidism, using ioPTH measurements during their first operation. Sensitivity and specificity rates of ioPTH measurements were 98% and 89%, respectively. The ioPTH test accurately indicated incomplete removal of all hyperfunctioning parathyroid tissue in 8 patients (12%). Five patients (8%) were re-explored immediately, of whom 4 were successfully treated in this single operative session. One patient was operated on successfully the next day. Two patients were operated on with a successful result during a second admission. In all the ioPTH measurements there was 1 false-positive result (1.5%) and 1 false-negative result (1.5%). The mean postoperative calcium value for the successfully treated patients was 2.34 mmol/l (range 2.14 - 2.71 mmol/l, normal range 2.20 - 2.65 mmol/l). The mean postoperative PTH level for the successfully treated patients was 3.76 pmol/l (range 0.40 - 7.1 pmol/l). CONCLUSION: Our data suggest that ioPTH measurements are feasible and useful in a non-academic hospital.

Surgeon-performed ultrasound as preoperative localization study in patients with primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy is the treatment of choice for single-gland primary hyperparathyroidism. However, the exact location of the abnormal gland has to be established. Sestamibi scintigraphy, computed tomography and ultrasound (US) are commonly used modalities. We describe our experience in a non-academic center with surgeon-performed US (S-US) of the neck as preoperative localization study in patients with primary hyperparathyroidism (PHPT). METHODS: Patients with a biochemically proven diagnosis of PHPT and preoperative S-US were included. Data were recorded prospectively. Perioperative gland location was compared to the preoperative S-US to determine sensitivity, specificity and accuracy rates. RESULTS: Two of the 50 patients who underwent S-US were not subjected to surgery. In 85% of the patients analyzed by S-US, the appropriate abnormal gland(s) were identified. In 11%, no gland was identified, but abnormal glands were found during surgery. Sensitivity of S-US in our hospital is 85%, with a positive predictive value of 97%. CONCLUSIONS: We achieved a satisfactory sensitivity rate. S-US provides anatomic information to the surgeon which enables a more detailed operation planning, and it is a valuable diagnostic modality for patients with PHPT in our opinion. We hope that our data encourage other centers to implement this technique as well.

Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy.

BACKGROUND AND PURPOSE: 5-aminosalicylate (5-ASA) raises levels of 6-thioguanine nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN - 6-thioguanosine mono-, di- and triphosphate (6-TGMP, 6-TGDP, 6-TGTP) - and of 6-methylmercaptopurine ribonucleotides (6-MMPR) after 5-ASA are not known. EXPERIMENTAL APPROACH: Effects of increasing 5-ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4-week study periods. Patients started with 2 g 5-ASA daily, and then were increased to 4 g daily and followed by a washout period. Thiopurine doses remained unchanged throughout the entire study. Levels of 6-TGMP, 6-TGDP, 6-TGTP and 6-MMPR as well as of 5-ASA and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) were determined each study period. KEY RESULTS: Median baseline levels in 17 patients of 6-TGDP, 6-TGTP and 6-MMPR were 52, 319 and 1676 pmol per 8 x 10(8) red blood cells respectively. After co-administration of 2 g 5-ASA daily, median 6-TGDP and 6-TGTP levels increased but median 6-MMPR levels were unchanged. Increasing 5-ASA to 4 g daily did not affect median 6-TGDP and 6-TGTP levels, but median 6-MMPR levels decreased. After discontinuation of 5-ASA, both 6-TGDP and 6-TGTP levels decreased and median 6-MMPR levels increased. The 6-TGTP/(6-TGDP+6-TGTP)-ratio did not change during the study, but 6-MMPR/6-TGN ratios decreased. CONCLUSIONS AND IMPLICATIONS: Individual 6-TGN metabolites increased after addition of 5-ASA, but 6-MMPR-levels and the 6-MMPR/6-TGN ratios decreased. Further studies are needed to decide whether this pharmacokinetic interaction would result in improvement of efficacy and/or increased risk of toxicity of AZA.

Limited stability of thiopurine metabolites in blood samples: relevant in research and clinical practise.

BACKGROUND: Monitoring of thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) is used to assess compliance and explain adverse reactions in IBD-patients. Correlations between dosage, metabolite concentrations and therapeutic efficacy or toxicity are contradictive. Research is complicated by analytical problems as matrices analyzed and analytical procedures vary widely. Moreover, stability of thiopurine metabolites is not well documented, yet pivotal for interpretation of analytical outcomes. Therefore, we prospectively investigated metabolite stability in blood samples under standard storage conditions. METHODS: Stability at room temperature and refrigeration (22 degrees C, 4 degrees C) was investigated during 1 week and frozen samples (-20 degrees C, -80 degrees C) were analyzed during 6 months storage. Ten patient samples were analyzed for each study period. RESULTS: Median 6-TGN concentrations on day 7 decreased significantly to 53% and 90% during storage at ambient temperature or refrigeration. Median 6-MMP concentrations on day 7 decreased significantly to 55% and 86%, respectively. Samples stored at -20 degrees C also showed significant decreases in both 6-TGN and 6-MMP in comparison with baseline values. At -80 degrees C, only 6-MMP showed a significant decrease in values compared to baseline. CONCLUSION: The stability of thiopurine metabolites is clearly a limiting factor in studies investigating utilisation of TDM and correlations with therapeutic outcome in IBD-patients. This has to be accounted for in clinical practice and (multi-center) trials investigating thiopurine drugs.

Brain abnormalities on MR imaging in patients with retinoblastoma.

BACKGROUND AND PURPOSE: Although pineoblastoma is the main brain abnormality associated with hereditary retinoblastoma, recent studies suggest an association with pineal cysts. This association is important because some pineoblastomas mimic pineal cysts. If there is a relationship, then radiologists should be aware of it because diagnostic confusion is possible. Mental retardation and congenital brain anomalies are also reported in patients with retinoblastoma, mostly in combination with 13q deletion syndrome. In this retrospective study, the presence of brain abnormalities on MR images in a large group of consecutive patients with retinoblastoma is evaluated. MATERIALS AND METHODS: Brain MR images of 168 patients with retinoblastoma from 1989 to 2009 were evaluated by 2 radiologists for tumors, structural anomalies, myelinization, and coincidental findings. Clinical records were reviewed for laterality, heredity, and the presence of the 13q deletion syndrome. RESULTS: The hereditary group (patients with bilateral and unilateral proved RB1-germline mutation) included 90 (54%) of 168 patients. Seven patients had 13q deletion syndrome. Normal findings on brain MR images were seen in 150 (89%) patients. Five pineoblastomas were detected, all in patients with hereditary retinoblastoma (5.5% in the hereditary subgroup). Nine pineal cysts were detected (2.2% in the hereditary subgroup). Corpus callosum agenesis was found in 1 patient and a Dandy-Walker variant in 1 patient, both in combination with 13q deletion syndrome. CONCLUSIONS: Pineoblastoma is associated with hereditary retinoblastoma, and structural brain abnormalities are restricted to patients with the 13q deletion syndrome. The incidence of pineal cysts in patients with retinoblastomas is similar to that in healthy children and is not associated with hereditary retinoblastoma.

Contrast-enhancement of the anterior eye segment in patients with retinoblastoma: correlation between clinical, MR imaging, and histopathologic findings.

BACKGROUND AND PURPOSE: AES contrast-enhancement is recognized in a substantial number of retinoblastoma-affected eyes. We retrospectively investigated the histopathologic basis of AES contrast-enhancement on MR images in retinoblastoma. MATERIALS AND METHODS: Pretreatment contrast-enhanced MR images were obtained from 42 children with retinoblastoma. Forty-two enucleated eyes were included in this study, AES enhancement was evaluated by using a 3-point score, and these data were correlated with clinical, MR imaging, and histopathologic findings. Additionally, 14 specimens were immunohistochemically analyzed for CD31, VEGF, and Flt-1 expression. Statistical correlations with AES enhancement were assessed by using a linear-by-linear association test and univariate and multivariate ordinal regressions. RESULTS: The degree of abnormal AES enhancement was moderate in 15 (36%) eyes and strong in 14 (33%) eyes, whereas 13 (31%) eyes showed normal AES enhancement. In multivariate analysis, the degree of AES enhancement showed statistically significant correlations with iris surface-vessel count (P = .05) and optic nerve invasion (P = .04) in the enucleated eye and with tumor volume (P = .02) as detected on MR imaging. No significant associations between AES enhancement and VEGF expression in the iris were observed. Flt-1 (P = .04) staining in iris stroma and IA as detected with CD31 staining (P = .009) both yielded a statistically significant positive correlation with abnormal AES enhancement. CONCLUSIONS: The degree of abnormal AES enhancement on MR imaging in retinoblastoma reflects angiogenesis in the iris. AES enhancement is also a hallmark of advanced retinoblastoma because its degree correlates with tumor volume and optic nerve invasion.

Validation of 70-gene prognosis signature in node-negative breast cancer.

PURPOSE: The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530-536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. METHODS: We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). RESULTS: The 5-year OS was 82 +/- 5% in poor (48%) and 97 +/- 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P = 0.021). The 5-years DMFP was 78 +/- 6% in poor and 98 +/- 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 +/- 5% and 94 +/- 3% (HR 10.7; 95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 +/- 6% in poor and 86 +/- 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. CONCLUSION: The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.

Helicobacter genotyping and detection in peroperative lavage fluid in patients with perforated peptic ulcer.

INTRODUCTION AND OBJECTIVES: Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are present in patients with PPU and which genotype is dominant in this population. The secondary aim was to study the possibility of determining the H. pylori status in a way other than by biopsy. MATERIALS AND METHODS: Serum samples, gastric tissue biopsies, lavage fluid, and fluid from the nasogastric tube were collected from patients operated upon for PPU. By means of PCR, DEIA, and LIPA the presence of the "cytotoxin associated gene" (cagA) and the genotype of the "vacuolating cytotoxin gene" were determined. RESULTS: Fluid from the nasogastric tube was obtained from 25 patients, lavage fluid from 26 patients, serum samples from 20 patients and biopsies from 18 patients. Several genotypes were found, of which the vacA s1 cagA positive strains were predominant. Additionally, a correlation was found between the H. pylori presence in biopsy and its presence in lavage fluid (p=0.015), rendering the latter as an alternative for biopsy. Sensitivity and specificity of lavage fluid analysis were 100% and 67%, respectively. CONCLUSION: This study shows the vacA s1 cagA positive strain is predominant in a PPU population. The correlation found between the H. pylori presence in biopsy and its presence in lavage fluid suggests that analysis of the lavage fluid is sufficient to determine the H. pylori presence. Risks associated with biopsy taking may be avoided.