Skin cancer risk in BRCA1/2 mutation carriers.

Women with BRCA1/2 mutations have an elevated risk of breast and ovarian cancer. These patients and their clinicians are often concerned about their risk for other cancers, including skin cancer. Research evaluating the association between BRCA1/2 mutations and skin cancer is limited and has produced inconsistent results. Herein, we review the current literature on the risk of melanoma and nonmelanoma skin cancers in BRCA1/2 mutation carriers. No studies have shown a statistically significant risk of melanoma in BRCA1 families. BRCA2 mutations have been linked to melanoma in large breast and ovarian cancer families, though a statistically significant elevated risk was reported in only one study. Five additional studies have shown some association between BRCA2 mutations and melanoma, while four studies did not find any association. With respect to nonmelanoma skin cancers, studies have produced conflicting results. Given the current state of medical knowledge, there is insufficient evidence to warrant increased skin cancer surveillance of patients with a confirmed BRCA1/2 mutation or a family history of a BRCA1/2 mutation, in the absence of standard risk factors. Nonetheless, suspected BRCA1/2 mutation carriers should be counselled about skin cancer risks and may benefit from yearly full skin examinations.

Radiological anatomy - evaluation of integrative education in radiology.

PURPOSE: Evaluation and analysis of the integrative course "Radiological Anatomy" established since 2007 at the Medical School Hannover (MHH) in comparison with conventional education. MATERIALS AND METHODS: Anatomy and radiology are usually taught separately with a considerable time lag. Interdisciplinary teaching of these associated subjects seems logical for several reasons. Therefore, the integrative course "Radiological Anatomy" was established in the second year of medical education, combining these two closely related subjects. This interdisciplinary course was retrospectively evaluated by consideration of a student questionnaire and staff observations. The advantages and disadvantages of integrative teaching in medical education are discussed. RESULTS: The course ratings were excellent (median 1; mean 1.3 on a scale of 1 to 6). This is significantly (p < 0.001) better than the average of all evaluated courses in the respective term (grade 2.8). The course improved the anatomical comprehension (90 %) and the students stated that the topics were relevant for their future medical education (90 %). Furthermore, interest in the subject's anatomy and radiology increased during the course (88 %). According to the students' suggestions the course was enhanced by a visitation in the Department of Radiology and the additional topic central nervous system. CONCLUSION: Integrative teaching of anatomy and radiology was well received by the students. Both, anatomical and radiological comprehension and the motivation to learn were improved. However, it should be considered, that the amount of work and time required by the teaching staff is considerably increased compared to traditional teaching.

Genetic architecture of prostate cancer in the Ashkenazi Jewish population.

BACKGROUND: Recently, numerous prostate cancer risk loci have been identified, some of which show association in specific populations. No study has yet investigated whether these single nucleotide polymorphisms (SNPs) are associated with prostate cancer in the Ashkenazi Jewish (AJ) population. METHODS: A total of 29 known prostate cancer risk SNPs were genotyped in 963 prostate cancer cases and 613 controls of AJ ancestry. These data were combined with data from 1241 additional Ashkenazi controls and tested for association with prostate cancer. Correction for multiple testing was performed using the false discovery rate procedure. RESULTS: Ten of twenty-three SNPs that passed quality control procedures were associated with prostate cancer risk at a false discovery rate of 5%. Of these, nine were originally discovered in studies of individuals of European ancestry. Based on power calculations, the number of significant associations observed is not surprising. CONCLUSION: We see no convincing evidence that the genetic architecture of prostate cancer in the AJ population is substantively different from that observed in other populations of European ancestry.

Relative contributions of BRCA1 and BRCA2 mutations to "triple-negative" breast cancer in Ashkenazi Women.

Approximately 10% of Ashkenazi Jewish (AJ) women with breast cancer (BC) carry a founder mutation in BRCA1 or BRCA2. There is an association between BRCA1 mutations and "triple-negative" breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative]. We sought to determine the predictive value of the TNBC phenotype for the presence of a BRCA mutation in AJ women ascertained without respect to family history. DNA samples were collected between 8/2000 and 6/2004 from a prevalent cohort of unselected AJ women with breast cancer (median age at diagnosis 56 years). Samples (n = 451) were genotyped for AJ founder mutations. 352 (78.0%) cancers were ER positive, 254 (56.3%) PR positive, and 91 (20.2%) ER negative/PR negative. 63 (14.0%) cancers were HER2 positive (immunohistochemistry 3+ or FISH >2.2). TNBC was observed in 64 patients (14.2%). Founder mutations were detected in 48 samples (10.6%) including 25/64 TNBC (39.1%; 19 BRCA1, 6 BRCA2). Among TNBC patients with family history (FH) information, 6/15 (40%) mutations were found in women without breast or ovarian cancer in a close relative. The positive predictive value of TNBC for a BRCA1 mutation was 30% overall, 50% in women diagnosed<50 years, and 14% in women diagnosed ≥50. TNBC was significantly associated with detecting a mutation in either BRCA1 or BRCA2, but only 25/52 (48%) mutation-associated cancers were TNBC. The prevalence of BRCA founder mutations exceeds 50% in subsets of AJ women with TNBC. FH is an imperfect predictor of mutation status in this group. A significant number of mutation-associated TNBC are due to BRCA2.

Discriminatory accuracy and potential clinical utility of genomic profiling for breast cancer risk in BRCA-negative women.

Several single nucleotide polymorphisms (SNPs) are associated with an increased risk of breast cancer. The clinical utility of genotyping individuals at these loci is not known. Subjects were 519 unaffected women without BRCA mutations. Gail, Claus, and IBIS models were used to estimate absolute breast cancer risks. Subjects were then genotyped at 15 independent risk loci. Published per-allele and genotype-specific odds ratios were used to calculate the composite cumulative genomic risk (CGR) for each subject. Affected age- and ethnicity-matched BRCA mutation-negative women were also genotyped as a comparison group for the calculation of discriminatory accuracy. The CGR was used to adjust absolute breast cancer risks calculated by Gail, Claus and IBIS models to determine the proportion of subjects whose recommendations for chemoprevention or MRI screening might be altered (reclassified) by such adjustment. Mean lifetime breast cancer risks calculated using the Gail, Claus, and IBIS models were 19.4, 13.0, and 17.7%, respectively. CGR did not correlate with breast cancer risk as calculated using any model. CGR was significantly higher in affected women (mean 3.35 vs. 3.12, P = 0.009). The discriminatory accuracy of the CGR alone was 0.55 (SE 0.019; P = 0.006). CGR adjustment of model-derived absolute risk estimates would have altered clinical recommendations for chemoprevention in 11-19% of subjects and for MRI screening in 8-32%. CGR has limited discriminatory accuracy. However, the use of a genomic risk term to adjust model-derived estimates has the potential to alter individual recommendations. These observations warrant investigation to evaluate the calibration of adjusted risk estimates.

A bitter pill to swallow.

Foreign body aspiration can be a life-threatening emergency requiring immediate intervention. However, unlike in children, clinical presentation of foreign bodies in adults often varies with regard to symptoms and signs and occurs without asphyxia. We here describe the case of a 65-year-old man on maintenance hemodialysis who developed dyspnea and left chest aspiration pneumonia after swallowing one tablet of the phosphate binder sevelamer. This case illustrates that elderly patients with swallowing complaints should be taken serious when they complain about their subsequent frustration of ingestion of their pills.

[Suspicion of a newly appearing hypertrophic obstructive cardiomyopathy in a patient treated for hepatocellular carcinoma]. / Verdacht auf neu aufgetretene hypertrophe obstruktive Kardiomyopathie bei hepatozellulärem Karzinom.

HISTORY AND ADMISSION FINDINGS: A 42-year-old women presented with shortness of breath, tachycardia and weakness to our department. Five years ago she had been diagnosed with hepatocellular carcinoma for which an extended hemihepatectomy had been performed. INVESTIGATIONS, DIAGNOSIS AND TREATMENT: The clinical examination revealed a systolic murmur over the artic region. Echocardiography showed an hypertrophed interventricular septum with signs like those in hypertrophic obstructive cardiomyopathy. Ultrasound demonstrated a cystic mass in the pelvis highly suspicious of a metastasis of a hepatocellular carcinoma. Fine needle biopsy confirmed the diagnosis of a metastatic lesion of hepatocellular carcinoma. Computed tomography demonstrated metastase in the lung and a space-occupying in the interventricular septum. The patients underwent resection of the lung and pelvic metastasis and died a few weeks later. CONCLUSION: This case demonstrates the rare occurence of a metastasis to the heart, imitating obstructive cardiac myopathy, in a patient with hepatocellular carcinoma.

Accuracy of navigated surgery of the pelvis after surface matching with an a-mode ultrasound probe.

Computer-aided surgery (CAS) allows for real-time intraoperative feedback resulting in increased accuracy, while reducing intraoperative radiation. CAS is especially useful for the treatment of certain pelvic ring fractures, which necessitate the precise placement of screws. Flouroscopy-based CAS modules have been developed for many orthopedic applications. The integration of the isocentric flouroscope even enables navigation using intraoperatively acquired three-dimensional (3D) data, though the scan volume and imaging quality are limited. Complicated and comprehensive pathologies in regions like the pelvis can necessitate a CT-based navigation system because of its larger field of view. To be accurate, the patient's anatomy must be registered and matched with the virtual object (CT data). The actual precision within the region of interest depends on the area of the bone where surface matching is performed. Conventional surface matching with a solid pointer requires extensive soft tissue dissection. This contradicts the primary purpose of CAS as a minimally invasive alternative to conventional surgical techniques. We therefore integrated an a-mode ultrasound pointer into the process of surface matching for pelvic surgery and compared it to the conventional method. Accuracy measurements were made in two pelvic models: a foam model submerged in water and one with attached porcine muscle tissue. Three different tissue depths were selected based on CT scans of 30 human pelves. The ultrasound pointer allowed for registration of virtually any point on the pelvis. This method of surface matching could be successfully integrated into CAS of the pelvis.

[A-mode ultrasonic pointer for navigated pelvic surgery]. / A-Mode-Ultraschall-Pointer für die navigierte Beckenchirurgie.

Surgical navigation has proven to be a minimally invasive procedure that enables precise surgical interventions with reduced exposure to irradiation for patient and personnel. Fluoroscopy-based modules have prevailed on the market. For certain operations of the pelvis computed tomography is necessary with its high imaging quality and considerably larger scan volume. To enable navigation in these cases, matching of the CT data set and the patient's real pelvic bone is essential. The common pair point-matching algorithm is complemented by the surface-matching algorithm to achieve an even higher overall precision of the system. For conventional surface matching with a solid pointer, the bone has to be exposed from soft tissue quite extensively, using a solid pointer. This conflicts with the claim of computer-assisted surgery to be minimally invasive. We integrated an A-mode ultrasonic pointer with the intention to perform extended surface matching on the pelvic bone noninvasively. Related to the conventional method, comparable and to some extent even improved precision conditions could be established.

Making sense of muscle fatigue and liver lesions.

Muscle weakness is a common complaint in clinical practice. If this symptom is combined with focal liver lesions there is a broad spectrum of differential diagnoses for the gastroenterologist to consider. Tumors of neuroendocrine origin such as small-cell lung carcinoma (SCLC) produce a wide array of peptide hormones and are common causes of paraneoplastic syndromes. We report on a 68-year-old woman who presented with progressing muscle fatigue and multiple liver lesions on ultrasonography. Hypertension, hyperglycemia, hypokalemia and metabolic alkalosis prompted consideration of underlying hypercortisolism. Further work-up demonstrated an acute ectopic ACTH syndrome as paraneoplastic manifestation of a small cell lung carcinoma. The woman deteriorated rapidly and finally died from intracranial tumor spread and septic complications. This case stresses the diagnostic and therapeutic difficulties of acute ectopic ACTH syndrome in the setting of SCLC.

[Anterior column fracture of the acetabulum with dorsal impression. Operative management by means of surgical dislocation of the hip]. / Vordere Pfeilerfraktur des Acetabulums mit dorsaler Impression. Operatives Management mittels chirurgischer Hüftluxation.

An unusual case of an anterior column fracture of the acetabulum with extended marginal impaction at the posterior column is presented. Fracture fixation was primarily performed by an ilioinguinal approach followed by a posterior approach with surgical dislocation of the hip to reduce the impacted fragments.

Accuracy of BRCA1 and BRCA2 founder mutation analysis in formalin-fixed and paraffin-embedded (FFPE) tissue.

BACKGROUND: A major limitation in counseling unaffected women from families with inherited breast and ovarian cancer is that a "true-negative" interpretation of wild type BRCA analysis of the proband cannot be inferred in the absence of demonstration of a BRCA mutation segregating in the kindred. Documentation of familial BRCA mutations from paraffin-derived DNA of deceased patients has been limited due to reports of technical complications leading to lack of reproducibility of BRCA testing of archival material. METHODS: DNA was extracted from formalin-fixed paraffin-embedded (FFPE) morphologically normal tissue of 161 blinded, coded samples from women previously genotyped for the three Ashkenazi Jewish BRCA founder mutations from lymphocyte-derived DNA. Multiplex PCR followed by denaturing polyacrylamide gel electrophoresis was performed for the three founder mutations to determine if analysis on FFPE tissue could produce results concordant with those of the lymphocyte-derived DNA. RESULTS: After disclosure of the sample codes, the results were compared with the original lymphocyte-derived DNA genotypes. Excluding one sample unevaluable due to PCR failure, there was 100% concordance of 160 genotypes (120 mutation samples) derived from DNA from archival FFPE tissue compared to peripheral lymphocytes. CONCLUSIONS: The method described reliably detected BRCA founder mutations in archival DNA derived from FFPE tissue. These results suggests that this technique may be useful in clinical settings to inform wild type BRCA results of unaffected probands, leading to avoidance of unnecessary intensified surveillance or risk-reducing surgery. With further validation this approach can also be applied to other populations where founder mutations are observed.

Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.

AIMS: Transarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). METHODS: Seventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600-1200 mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100 mg/m2) and doxorubicin (60 mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. RESULTS: Tumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). CONCLUSION: TACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

[Laser measuring device for phonation]. / Geschwindigkeitsmessung der stimmlippenbewegung.

INTRODUCTION: Clinical examinations with short-interval, color-filtered double-flash stroboscopy enable us to estimate the movements of the vocal fold edges during phonation. So-called 'displacement bands' show the degree of the vibratory amplitude in these images. Using the two-point light projection method the displacement bands can be measured with very high accuracy. A combination of these two methods was used for velocity measurements of the vocal fold movements within the phonatory cycle. The aim of the study was to explore the influence of change in sound pressure level (SPL) and fundamental frequency (F0) on the velocity of the horizontal amplitude of the vocal folds during phonation. MATERIAL AND METHODS: 40 healthy volunteers (31 women, 9 men, average age 24.8 years) were examined. During the special videostroboscopy with short-interval, color-filtered double flashes laser spots were projected onto the vocal folds by an endoscopic two-point light projection device. The subjects had to change their SPL and F0 following a test protocol. During phonation they had to produce tones in low, middle and high chest voice as well as in falsetto register. Each subject was asked to do this in a soft, a modal, a loud and a very loud manner. Images of the phonatory cycle showing the vocal folds immediately before collision were measured separately at three different positions. About 15,000 single measurements were evaluated. RESULTS: The measured velocity of the horizontal amplitude during the closing phase of the vocal folds in chest voice was 30-160 cm/s. An increase in SPL resulted in an increasing velocity of the displacement bands. A change in F0 did not lead to statistically relevant changes in the measured velocity. CONCLUSION: A combination of short-interval, color-filtered double-flash stroboscopy and a two-point light projection method enables measurements of the velocity of vocal fold movements. The SPL is the important factor for the velocity change within the phonatory cycle. F0 seems not to covary with the velocity of the horizontal amplitude during the closing phase of the phonatory cycle.

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child-Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received.

[Clinical application of the endolaryngeal laser measurement technique]. / Klinischer Einsatz der endolaryngealen Laservermessungstechnik.

INTRODUCTION: Laser projection techniques have made morphometric measurement of laryngeal structures possible. The clinical application of a new laser measurement technique that uses a double reflecting mirror for laser beam duplication is discussed. MATERIAL AND METHODS: Endolaryngeal measurement with a new two-point laser light projection method was carried out on 25 patients with ten different organic lesions of the vocal folds. The laser measurement tool can be clipped onto the shaft of a rigid endoscope. A special software program enables quick and precise measurements of distances and areas that are in the same horizontal plane as the laser spots. FINDINGS: Using this new system, a clinical examination of the size of organic lesions of the vocal folds is possible, with a precise measurement of endolaryngeal structures being possible in all cases. The findings are easily documented, and the examinations can take place during routine laryngoscopic investigations. CONCLUSION: Systems for endolaryngeal measurements enable morphometric measurements within the larynx. Quantitative examinations have become possible in laryngology.

[Transcutaneous perianal ultrasound (PAUS) for the imaging of fistulas and abscesses in Crohn's disease]. / Aktuelle Sonographie: Transkutaner, perianaler Ultraschall (PAUS) zur Diagnostik von Fisteln und Abszessen bei M. Crohn.

Pelvic MRI and transanal ultrasound constitute the gold standard for the imaging of perianal inflammatory lesions in Crohn's disease. Perianal ultrasound (PAUS), however, is rarely considered in recent literature. In contrast to the established methods, perianal ultrasound represents an easy, cost-effective and at the same time sensitive method for the imaging of perianal abscesses and fistulas. This article illustrates the performance of perianal ultrasound and shows typical images of pathological findings such as abscesses and fistulas. PAUS is especially useful for acute diagnostics to rule out perianal abscesses and for follow-up evaluation of fistula treatment. For example, complications such as abscesses can be detected in a timely manner.

[Intraarterial calcium stimulation (ASVS) for pancreatic insulinoma: comparison of preoperative localization procedures]. / Der Kalziumstimulationstest (ASVS) bei Insulinomen des Pankreas: Vergleich mit der bildgebenden Lokalisationsdiagnostik.

PURPOSE: Evaluation of clinical relevance of the arterial stimulation procedure with venous sampling (ASVS) in the preoperative localization of insulinoma. METHODS: Thirteen patients with endogenous hyperinsulinism underwent preoperative transabdominal ultrasound (US), helical CT (CT), MRI, endoscopic ultrasound (EUS), and angiography (DSA) in conjunction with the ASVS-test for the detection of insulinoma. The results were compared with intraoperative findings, intraoperative ultrasound (IOUS) and histology. RESULTS: Sensitivity was as follows: US 8%, MRI 27%, CT 46%, EUS 50%,DSA 69%,and ASVS 92%. Intraoperative palpation and IOUS yielded a sensitivity of 77%. In 3 patients the tumors were neither palpable nor detectable by IOUS, the mode of resection was based on preoperative diagnostics. The ASVS procedure as a functional test was superior to all other modalities for the preoperative tumor detection. CONCLUSION: The ASVS was the most sensitive diagnostic modality. It should especially be considered in terms of health economical aspects when CT or MRI do not yield conclusive results.

[Physical and technical elements of short-interval, color-filtered double strobe flash-stroboscopy]. / Technisch-physikalische Grundlagen der Doppelbelichtungsstroboskopie.

INTRODUCTION: Quantitative measurement of vocal fold movements can be done either with high-speed imaging or with short interval, color-filtered double strobe flash-stroboscopy. The physical and technical elements of this new technique are described. METHODS: Two special strobe units (KAY Elemetrics RLS 9100) are used in a master-slave configuration. In this way an adjustable interval of 0.1-2.0 ms between flashes is introduced. The strobe flashes are color filtered and are separated by a brief interval. By this means a double exposure is created in each video frame.Real-time visualization of opening and closing velocities over the entire length of the vocal fold from anterior to posterior is possible. Quantification is possible off-line after image calibration. CONCLUSION: Short-interval, color-filtered double-strobe flash stroboscopy allows quantitative measurement of the velocity of vocal fold movements during vibration at different pitches and sound pressure levels (SPL). Images gained with this new technique provide information about a dynamic property (velocity) of the vocal fold within a single image.Therefore, its use could be helpful from the aspect of clinical documentation.