[Handheld Optical Coherence Tomography in Paediatric Ophthalmology: Experience of the Department of Ophthalmology in Giessen]. / Handgehaltene optische Kohärenztomografie in pädiatrischer Ophthalmologie: Erfahrung der Gießener Universitätsaugenklinik.

Introduction: Optical coherence tomography is an important tool for the imaging and analysis of retinal structures. The usability of conventional table-top devices is limited in children. We report on our experiences with a handheld Spectral Domain Optical Coherence Tomography (HH-SD-OCT, Bioptigen™) in infants and young children in our daily practice. Methods: Between October 2014 and April 2016, we investigated 259 patients. Indications and diagnoses were assessed. Individual examples are shown to demonstrate the advantages and disadvantages of the novel technique. Results: It was possible to examine 259 children of at least 7 weeks of age (median: 1.59 years; ± 1.32 SD) with a mean investigation time of 18.3 minutes (± 8.3 SD). The most frequent indication was retinal assessment in prematures (32.8 %). Nystagmus, retinal dystrophies, reduced visual acuity and albinism amounted to additional 37.4 % of all indications. Conclusions: Handheld OCT is a beneficial complement for diagnosis of diseases in paediatric ophthalmology. As a complement to established methods like wide-field fundus photography, HH-SD-OCT allows the physician to assess and follow-up new objective structural information. As the Bioptigen does not have an eye tracker, it is challenging to orient the scan in the posterior retinal pole, in particular in case of instable fixation. This complicates follow-up investigations, which can only be performed with additional high programming and analysis effort.

Redirection of doublecortin-positive cell migration by over-expression of the chemokines MCP-1, MIP-1α and GRO-α in the adult rat brain.

Inflammation-induced chemoattraction plays a major role in adult subventricular zone (SVZ)-derived precursor cell migration following neural cell loss, in particular through the release of chemokines by activated microglia and macrophages. We previously demonstrated that monocyte chemotactic protein-1 (MCP-1) (chemokine (c-c motif) ligand (CCL)2), macrophage inflammatory protein-1α (MIP-1α) (CCL3) and growth regulatory protein-α (GRO-α) (chemokine (c-x-c motif) ligand (CXCL)1) are up-regulated following neural cell loss in the adult striatum and act as potent chemoattractants for SVZ-derived precursor cells in vitro. Based on these observations, the current study aimed to examine the individual effect of MCP-1, MIP-1α and GRO-α on the migration of adult SVZ-derived neural precursor cells in vivo. To address this without the confounding effects of injury-induced chemotactic cues, adeno-associated viral (AAV)2-mediated in vivo gene transfer was used to ectopically express either MCP-1, MIP-1α or GRO-α, or the control red fluorescent protein (RFP) in the normal adult rat striatum. The extent of doublecortin (Dcx)-positive cell recruitment from the SVZ into the striatal parenchyma was then determined at 4 and 8weeks following AAV2 injection. Ectopic expression either of MCP-1 or MIP-1α in the normal adult rat brain significantly increased the number of Dcx-positive cells and the extent of their migration into the striatum at both 4 and 8weeks after vector injection but did not promote either precursor cell proliferation or neural differentiation. In contrast, while over-expression of GRO-α 4weeks after vector injection induced a significant increase in Dcx-positive cell migration compared to control, this effect was reduced to control levels by 8weeks post injection. Further, direct comparison between MCP-1, MIP-1α and GRO-α at both 4 and 8weeks post vector injection indicated that GRO-α may have a reduced effect in inducing Dcx-positive cell migration when compared to MCP-1. Combined, these results confirm that over-expression of the chemokines MCP-1, MIP-1α and GRO-α can override cues directing precursor cell migration along the rostral migratory stream (RMS) and provides a mechanism by which neural precursor cell migration can be redirected into a non-neurogenic region. Differences in the migratory effect observed between individual chemokine may be due to ligand-binding affinity and/or receptor expression on SVZ-derived precursor cells.

[Comparison of treatment expenses of naturopathic and orthopedic in-patient treatment]. / Kostenvergleichsuntersuchung zur naturheilkundlichen und konventionellen orthopädischen stationären Behandlung.

BACKGROUND: In health services research comparative studies between orthopaedics and naturopathy are necessary. They allow evidence based decisions between individual therapeutical alternatives as well as decisions on health politics, e.g. concerning allocation of resources. PATIENTS AND METHODS: A controlled prospective cohort study is presented. Conservatively treated patients were recruited for the study, if they needed in-patient treatment because of chronic back pain. The conservative orthopaedic treatment including Minimal invasive Therapy (MIT) was compared to in-patient naturopathic "complex"-treatment. The real costs to the public health insurance system are unknown--relating to both the individual patient and the physician. Hence an approximation was attempted on the basis of the billing of the concerned hospitals, the analysis of extensive patient interviews, randomly selected evaluation of in- and out-patient records, validated by an expert panel. RESULTS: Costs for medication decreased in the post stationary phase after orthopedic and naturopathic treatment. Rehabilitation measures and treatments at a health resort increased after orthopedic treatment, whereas the frequency of specialist consultation decreased in both cohorts indicating the efficacy of the in-patient treatment. Incidence of psychotherapy was highest in the naturopathic group before admission to hospital and decreased afterwards. The gathered data point to a reduction of the total outpatient treatment costs in both cohorts. There were treatment-specific differences when regarding single components. CONCLUSION: Naturopathic complex in-patient treatment is a cost-efficient complement of the conventional orthopedic treatment options.

[DiaPat urine test for prostate cancer. Predictive value for results of transrectal ultrasound-guided prostate biopsies]. / DiaPat-Prostatakarzinom-Urintest. Vorhersagekraft für das Ergebnis transrektal-sonographisch gesteuerter Prostatabiopsien.

BACKGROUND: A novel urine test for early detection of prostate cancer (PCA), distributed and marketed by the company DiaPat, is advertised by the statement "correct analysis in 9 of 10 cases." PATIENTS AND METHODS: The test separates urinary polypeptides by means of capillary electrophoresis and characterizes the peptides in a time-of-flight mass spectrometer. The DiaPat test was performed on the urine of 18 men prior to multiple ultrasound-guided prostate biopsies. RESULTS: Sixteen of the 18 samples met the requirements for sample quality as established by the manufacturer. Eight of these 16 urine samples had been collected from patients in whom biopsies consecutively detected PCA; the remaining eight patients had benign biopsy results. Among the eight patients with detected PCA, the urine test yielded a low probability for PCA in three cases and a high probability in five. Within the group of eight patients with benign biopsy results, the urine test predicted a high probability for PCA in five men and a low probability in three. For the given PCA incidence of 50% within the investigated population, the DiaPat test correctly predicted biopsy results in one half of the population, whereas prediction in the remaining half was incorrect. CONCLUSION: Unless reliable validation of the DiaPat urine test for PCA is available, no clinical consequences should be drawn from the test results.

Impact of comorbidities on post-prostatectomy incontinence.

INTRODUCTION: The aim of this retrospective study was to evaluate various factors that may influence post-prostatectomy incontinence (PPI). PATIENTS AND METHODS: 1,088 men with prostate cancer underwent radical retropubic prostatectomy. 742 patients were evaluable for analysis. Continence was defined as usage of no or one pad daily. Mean follow-up was 45 months (12-143). RESULTS: Based on protective pad requirement 100% and 76% of men were continent at baseline and at the time of questionnaire evaluation (at least 12 months), respectively. Univariate analysis was performed to identify factors that may influence the return of continence. Age, body mass index (BMI), previous TUR-P, smoking, hypertension, diabetes and attempted nerve sparing did not predict postoperative continence status. CONCLUSIONS: In contrast to several reports, our analysis revealed that age, BMI, previous TUR-P, smoking, hypertension and diabetes do not have a statistically significant impact on continence after radical retropubic prostatectomy and are therefore not useful as predictors for PPI.

Intussusception of bladder neck improves early continence after radical prostatectomy: results of a prospective trial.

OBJECTIVES: To evaluate the impact of intussusception of the bladder neck on post-radical prostatectomy incontinence. METHODS: A total of 272 men with organ-confined prostate cancer who had undergone radical retropubic prostatectomy were studied. Of the 272 men, 139 underwent bladder neck intussusception and 133 did not. Patients completed validated questionnaires IIQ-7 and a symptom inventory. Continence was defined as the use of no or only one pad daily. RESULTS: Of the 272 men, 100%, 98.5%, and 96% answered the questionnaire and urinary symptom inventory at baseline and 3 and 12 months postoperatively, respectively. According to the protective pad requirement, 100%, 60%, and 86% of patients without intussusception and 100%, 77%, and 83% of the patients with intussusception were continent at baseline and 3 and 12 months postoperatively, respectively. Univariate logistic regression analysis revealed a statistically significant impact of intussusception on postprostatectomy incontinence at 3 months (P = 0.009), although continence at 12 months did not differ significantly (P = 0.5). CONCLUSIONS: Intussusception of the bladder neck had a significant effect on regaining continence at 3 months, although continence at 12 months was not affected.

Serum DNA and urine DNA alterations of urinary transitional cell bladder carcinoma detected by fluorescent microsatellite analysis.

There are no reliable serologic tumor markers for transitional cell carcinoma (TCC) of the urinary bladder and noninvasive urine investigations are inadequate. We used fluorescent microsatellite analysis (MSA) to detect serum DNA and urine-sediment DNA alterations in patients with bladder cancer and prospectively collected fresh tumor, peripheral blood, serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. Fluorescent MSA was performed with 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q in the 39 cancer patients and in 10 healthy controls. Serum DNA alterations were identified in 84.5% (33 of 39 patients) and tumor-specific urine DNA alterations indicating the diagnosis were present in 72% (27 of 39 patients) of cases. None of the healthy controls displayed serum DNA alterations. The highest frequency of serum DNA aberrations (56%) was detected for chromosomal region 8p. The most frequent alterations in urine-sediment DNA, 36% and 26%, were detected in chromosomal regions 8p and 9p, respectively. Identification of serum DNA and urine-sediment DNA alterations was not related to stage of disease or grade of tumor (p > 0.05). Thus, MSA offers a highly sensitive and specific method for serum- and urine-bound diagnosis of bladder TCC.

Current status of cytotoxic chemotherapy in hormone refractory prostate cancer.

Adenocarcinoma of the prostate is the most prevalent neoplastic disease in men and continues to be a major cause of morbidity and mortality. Death from prostate cancer is associated with objective and biochemical progression following hormonal manipulations often described as hormone refractory prostate cancer (HRPCA). Therapy for HRPCA is primarily palliative and therapeutic efficacy has to be balanced against potential treatment-related side effects. Therapeutic efficacy may be assessed by evaluating the percentage of patients obtaining a PSA decline of > 50%, evaluating the response of bidimensionally measurable disease or by improvements in quality of life assessments. The most effective cytotoxic therapies at the present time seem to be combinations of estramustine phosphate with taxanes and etoposide. Regimes employing ketoconazole with estramustine, vinblastine or bisphosphonates seem to be worthy of further evaluation. Mitoxantrone has an impressive palliative effect in patients, particularly when combined with hydrocortisone. Oral chemotherapeutic regimens with a combination of estramustine phosphate, cyclophosphamide and prednisone appear to offer a less toxic alternative. For the future we need prospective randomized clinical phase-III studies, prognosticators identifying patients as being at high or low risk who might benefit from different therapeutic approaches and generally binding eligibility and response guidelines in order to be able to compare trials of different therapeutic approaches.

Management of contralateral adrenal metastasis from renal cell carcinoma: possibility of inferior vena cava tumour thrombus.

OBJECTIVE: The contralateral adrenal gland is a rare metastatic site in renal cell carcinoma (RCC). We describe our experiences with this metastasis in a cohort of 610 radical nephrectomy patients analysed. To our knowledge this study is the first to demonstrate an inferior vena cava tumour thrombus from metachronous contralateral adrenal metastasis. PATIENTS AND METHODS: After radical nephrectomy for RCC, 610 patients treated at our institution from 1985-99 were retrospectively investigated for the incidence of contralateral adrenal metastasis, additional clinical findings, treatment modalities and survival after treatment for contralateral adrenal gland metastasis. RESULTS: The incidence of contralateral adrenal metastasis was 1.1% (7/610 patients), while the incidence of ipsilateral metastasis was 3.4% (21/610). In 3 of 7 cases the contralateral adrenal metastasis occurred simultaneously with primary RCC in the kidney. The contralateral adrenal gland was affected by distant tumour spread metachronously in 4 of 7 cases (3/4 bilateral adrenal involvement, 1/4 unilateral disease). In 1 case a metachronous contralateral adrenal metastasis caused vena cava tumour thrombus by propagation via the suprarenal venous route. After a mean follow-up of 20 months (range 1-54 months), 4 of 6 patients showed no evidence of disease after contralateral adrenalectomy. CONCLUSIONS: The probability of contralateral adrenal metastasis from RCC is 1.1%. Adrenalectomy in these cases offers a good chance of cure. In 71% of cases contralateral adrenal metastasis occurs in conjunction with ipsilateral disease, which provides a strong argument for routine ipsilateral adrenalectomy during radical nephrectomy. Care must be taken in preoperative diagnostics, as metachronous adrenal metastasis is capable of causing vena cava tumour thrombus.

Allelic changes at multiple regions of chromosome 5 are associated with progression of urinary bladder cancer.

This study has analysed 65 urothelial carcinomas for allelic imbalance at 22 loci of chromosome 5 and has determined three regions of interest. A commonly duplicated region was mapped to chromosome 5p between loci D5S1473 and D5S819, one region of deletion to chromosome 5q22-23 between loci D5S2055 and D5S659, and another to chromosome 5q33-34 between loci D5S1456 and D5S1465. An allelic imbalance was detected in 54% of the cases. Only 10% of grade 1 tumours showed allelic changes at chromosome 5, whereas 60% and 63% of grade 2 and grade 3 cancers, respectively, had alterations of chromosome 5. The frequency of chromosome 5 changes increased from 24% in pTa tumours up to 72% in pT3-4 tumours. Of particular interest, ten out of 12 urothelial carcinomas showing metastatic growth in regional lymph nodes at the time of cystectomy had alterations at chromosome 5. No specific region, but genetic changes in general were associated with the grading and staging of bladder cancers.

Radical nephrectomy for renal cell carcinoma: Is adrenalectomy necessary?

OBJECTIVES: The role of simultaneous adrenalectomy in combination with radical nephrectomy in the treatment for renal cell carcinoma (RCC) remains controversial. With nephron-sparing surgery being commonly applied, the indication for adrenalectomy has to be critically assessed. PATIENTS AND METHODS: In a retrospective analysis the outcome of 589 patients, who underwent ipsilateral adrenalectomy along with radical nephrectomy in the treatment for RCC between 1985 and 1997 at our institution, was evaluated. The mean follow-up time was 34 months (range 1-95). RESULTS: Histologically an ipsilateral adrenal metastasis was found in 19/589 patients (3.2%). 16/19 patients had >/= T3, 3/19 had T1 tumours. The average size of the primary tumours with adrenal metastasis was 7.8 cm (range 2.3-13) in diameter with no preferential primary tumour site within the kidney (6/19 upper, 4/19 middle and 9/19 lower third). Only 4/19 patients had suspect adrenal findings in preoperative diagnostics (ultrasound, CT scan). 6/19 (31.5%) patients with adrenal metastasis are alive without evidence of disease at a mean of 41 months (range 11-95) after surgery for RCC. CONCLUSIONS: The probability of adrenal metastasis correlates with primary tumour stage, but not with its location within the kidney. The preoperative diagnostics are not reliable concerning small adrenal metastases. We thus still recommend simultaneous adrenalectomy in those cases where radical nephrectomy in patients with RCC is indicated.

Microsatellite analysis reveals deletion of a large region at chromosome 8p in conventional renal cell carcinoma.

Loss of heterozygosity (LOH) at chromosome 8p is associated with the progression of conventional (non-papillary) renal cell carcinomas (RCC). To determine the tumor suppressor gene locus, we carried out a deletion mapping of chromosome 8p at 10 microsatellite loci in 96 RCCs. LOH occurred in 32% of the tumors. The smallest overlapping region of deletion at chromosome 8p11.2-p23.1 corresponds to approximately 34-cM genetic distance. No small interstitial deletion was seen.

Duplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours.

Previous karyotyping showed a combined trisomy of chromosome 7 and 17 in sporadic and hereditary papillary renal cell tumours (RCT). A recent molecular analysis revealed a mutation in the MET tyrosine kinase (chromosome 7q31) in the germline of four out of seven families with hereditary papillary RCT (HPRCT). We have analysed germline cells as well as multiple tumours obtained from HPRCT families and sporadic cases for alteration of the MET tyrosine kinase and for allelic duplication at chromosome 7 and 17. We have detected a germ line mutation in the MET tyrosine kinase in one of the two families with HPRCTs and also found the same mutation in the germ line of one patient with clinically recognized multiple, bilateral papillary RCTs but without family history. The mutant MET allele is consequently duplicated and overexpressed in tumour cells indicating that duplication of the mutant MET allele is necessary before cells enter the tumorigenic pathway. The lack of germline mutation in two members of another HPRT family and duplication of the same parental allele of chromosome 7 in multiple tumours suggests that a germ line event other than mutation of MET tyrosine kinase is involved in the development of these tumours. Duplication of different alleles of chromosome 7 in sporadic and of chromosome 17 in both types of tumours excludes a germline mutation at these chromosomal sites.

Duplication of two distinct regions on chromosome 5q in non-papillary renal-cell carcinomas.

RFLP studies have indicated a duplication of DNA sequences at the chromosome 5q22 region and showed a breakpoint cluster between the apc and mcc genes in nonpapillary renal-cell carcinoma (RCC). We have now made a high-density fluorescent microsatellite assay to investigate the allelic status and determine the smallest duplication at this region in 62 sporadic non-papillary RCCs. Duplication at each informative locus was found in 27 cases. Partial duplications in 3 tumors delineated 2 distinct regions. One was found at loci D5S659, D5S1720 and w2005 at chromosome band 5q22; this region partially overlaps with the smallest duplicated region found by previous RFLP analysis. Another small duplication was marked by loci D5S816 and D5S476 at chromosome band 5q31.1 and included the alpha-catenin gene (ctnna1).

[Early complications in treatment of femoral neck fractures. Experiences with Olmed screws]. / Tidlige komplikasjoner ved behandling av lårhalsbrudd. Erfaringer med Olmedskruer.

Postoperative secondary displacement of displaced femoral neck fractures is a major problem in the treatment of this fracture. In a study of 232 femoral neck fractures operated at the Department of Surgery, Harstad Hospital and at the Departments of Surgery and Orthopaedics, Tromsø University Hospital, the reduction was lost in 12% of the displaced fractures within three months. The fractures were fixated with two 6 mm screws (Olmed). The deep infection rate was 3.4%. There were significant differences between the hospitals. The rate of redisplacement was 5% at Harstad Hospital and 29% at the Tromsø University Hospital (p less than 0.001), the rate of deep infection was 1.8% versus 7.5% (p less than 0.05). Early complications are caused by poor quality of reduction and incorrect positioning of the screws. The surgeons' lack of experience in treating these fractures gives rise to a high rate of complications. The main reason for the low rate of complications in the material from Harstad Hospital is continuous and prospective quality control of femoral neck fractures. Such continuous feedback, and an interest intreating these fractures among the surgical staff, obviously improves the results. When the Olmed method of fixation is used correctly the rate of early complications is small.