Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer.

BACKGROUND: SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression. PATIENTS AND METHODS: Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m(2) i.v., days 1 and 8) and cisplatin (75 mg/m(2) i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors. RESULTS: A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine-cisplatin group than in the gemcitabine-cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus <1%) and skin rash (6% versus <1%). CONCLUSIONS: In line with SQUIRE ITT, addition of necitumumab to gemcitabine-cisplatin significantly prolonged OS and was generally well tolerated in the subpopulation of patients with EGFR-expressing advanced sq-NSCLC. The benefit from addition of necitumumab to chemotherapy was not apparent in this analysis for the small subgroup of patients with non-EGFR-expressing tumors. CLINICAL TRIAL: NCT00981058.

Prevention of incisional hernia with a reinforced tension line (RTL) versus primary suture only in midline laparotomies: 3-year follow-up in a randomized clinical trial.

PURPOSE: Incisional hernia (IH) has an incidence of 10-23%, which can increase to 38% in specific risk groups. The objective of this study is to report the results at 3 years of follow-up of the use of the reinforced tension line (RTL) technique compared with primary suture only (PSO) closure in the prevention of IH in high-risk patients undergoing laparotomy. METHODS: Open randomized controlled clinical trial. Included were patients older than 18 years who underwent midline laparotomy, emergency or scheduled, who were considered high risk, and who completed 3-year follow-up. The patients were randomized 1:1 to the RTL technique or to PSO. The objective was to report the incidence of IH and the complications associated with the closure method. Intention-to-treat analysis and Cox regression were performed. RESULTS: A total of 124 patients were randomized; 51 patients from the RTL group and 53 patients from the PSO group finished the 3-year follow-up. The incidence of IH was higher in the PSO group (15/53, 28.3%) than the RTL group (5/51, 9.8%) (p = 0.016, OR 0.35, 95% CI 0.14-0.88, number needed to treat 5.4, log-rank test p = 0.017). The groups were similar in the rates of surgical site infection, hematoma, seroma, and postoperative pain during follow-up. CONCLUSIONS: The RTL technique is useful in the prevention of IH when compared with PSO in high-risk midline laparotomy patients, and it is not associated with a higher percentage of complications. TRIAL REGISTRATION: Local Committee CI-HRAEB-2013-020. March 13, 2013. CLINICAL TRIALS: NCT02136628, retrospectively registered.

Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: a randomised, multicentre open-label phase II study.

BACKGROUND: Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin, cisplatin and capecitabine (ECX) chemotherapy in untreated advanced oesophago-gastric (OG) cancer. The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone. PATIENTS AND METHODS: In this multicentre, randomised open-label phase II study, 72 patients with metastatic OG cancer were randomly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m², cisplatin 60 mg/m² on day 1 and capecitabine 1250 mg/m² daily in a 21-day cycle (ECX) or the same ECX regimen alone. The primary end point was objective response. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life, safety and tolerability. RESULTS: Following random assignment, 35 patients (median age 59 years) received ECX/matuzumab and 36 patients (median age 64 years) ECX. The addition of matuzumab to ECX did not improve objective response: 31% for ECX/matuzumab [95% confidence interval (CI) 17-49] compared with 58% for the ECX arm (95% CI 41-74) P = 0.994 (one sided). There was no significant difference in median PFS: 4.8 months (95% CI 2.9-8.1) for ECX/matuzumab versus 7.1 months (95% CI 4.4-8.5) for ECX, or in median OS: 9.4 months (95% CI 7.5-16.2), compared with 12.2 months (95% CI 9.8-13.8 months). Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups, respectively. CONCLUSION: Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer. Therefore, ECX/matuzumab should not be examined further in phase III trials.

The Y chromosomal fertility factor Threads in Drosophila hydei harbors a functional gene encoding an axonemal dynein beta heavy chain protein.

To understand the contradiction between megabase-sized lampbrush loops and putative protein encoding genes both associated with the loci of Y chromosomal fertility genes of Drosophila on the molecular level, we used PCR-mediated cloning to identify and isolate the cDNA sequence of the Y chromosomal Drosophila hydei gene DhDhc7(Y). Alignment of the sequences of the putative protein DhDhc7(Y) and the outer arm dynein beta heavy chain protein DYH2 of Tripneustes gratilla shows homology over the entire length of the protein chains. Therefore the proteins can be assumed to fulfill orthologous functions within the sperm tail axonemes of both species. Functional dynein beta heavy chain molecules, however, are necessary for the assembly and attachment of outer dynein arms within the sperm tail axoneme. Localization of DhDhc7(Y) to the fertility factor Threads, comprising at least 5.1 Mb of transcriptionally active repetitive DNA, results from an infertile Threads- mutant where large clusters of Threads specifically transcribed satellites and parts of DhDhc7(Y) encoding sequences are missing simultaneously. Consequently, the complete lack of the outer dynein arms in Threads- males most probably causes sperm immotility and hence infertility of the fly. Moreover, preliminary sequence analysis and several other features support the hypothesis that DhDhc7(Y) on the lampbrush loops Threads in D. hydei and Dhc-Yh3 on the lampbrush loops kl-5 in Drosophila melanogaster on the heterochromatic Y chromosome of both species might indeed code for orthologous dynein beta heavy chain proteins.

Mega-introns in the dynein gene DhDhc7(Y) on the heterochromatic Y chromosome give rise to the giant threads loops in primary spermatocytes of Drosophila hydei.

The heterochromatic Y chromosomes of several Drosophila species harbor a small number of male fertility genes (fertility factors) with several unusual features. Expression of their megabase-sized loci is restricted to primary spermatocytes and correlates with the unfolding of species-specific lampbrush loop-like structures resulting from huge transcripts mainly derived from clusters of loop-specific Y chromosomal satellites. Otherwise, there is evidence from genetic mapping and biochemical experiments that at least two of these loops, Threads in Drosophila hydei and kl-5 in D. melanogaster, colocalize with the genes for the axonemal dynein beta heavy chain proteins DhDhc7(Y) and Dhc-Yh3, respectively. Here, we make use of particular Threads mutants with megabase-sized deletions for direct mapping of DhDhc7(Y)-specific exons among the large clusters of satellite DNA within the 5.1-Mb Threads transcription unit. PCR experiments with exon-specific primer pairs, in combination with hybridization experiments with exon- and satellite-specific probes on filters with large PFGE-generated DNA fragments, offer a simple solution for the long-lasting paradox between megabase-sized loops and protein-encoding transcription units; the lampbrush loops Threads and the DhDhc7(Y) gene are one and the same transcription unit, and the giant size of the DhDhc7(Y) gene as well as its appearance as a giant lampbrush loop are merely the result of transcription of huge clusters of satellite DNA within some of its 20 introns.

Her-2/neu expression in breast cancer--A comparison of different diagnostic methods.

BACKGROUND: Determination of Her-2/neu overexpression in breast cancer has previously been shown to be of prognostic significance. In this study, Her-2/neu expression in breast cancer was characterised by real-time PCR (RLT-PCR) based LightCycler-HER-2/neu DNA Quantification with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). MATERIAL AND METHODS: Fifteen specimens of invasive breast cancer - whole tissue sections as well as microdissected tumour cells - were subjected to RLT-PCR. Additionally, IHC and FISH were performed. RESULTS: Her-2/neu overexpression was detected by FISH and by real-time PCR in the same tumours. In contrast, IHC revealed discordant results. CONCLUSION: Determination of Her-2/neu amplification by real-time PCR is a sensitive and specific method with some advantages over FISH. This method is simple and reliable and has the potential of categorizing those tumours with borderline Her-2/neu overexpression as determined by IHC.

Detection of thyroid peroxidase mRNA in peripheral blood of patients with malignant and benign thyroid diseases.

The aim of this study was to evaluate thyroid peroxidase (TPO) mRNA expression in peripheral blood of patients with benign and malignant thyroid disease. Included were 120 thyroid cancer patients, 85 patients with goitre or Graves' disease (GD) and 54 healthy volunteers. TPO mRNA expression was analysed in peripheral blood by nested RT-PCR. In cancer patients, RT-PCR results were compared with staging, grading and serum thyroglobulin (TG) measurement. TPO transcripts were detected in 7/10 (70%) patients with known metastases of thyroid cancer and in 39 of 110 (36%) patients without metastases (P<0.05), in 15/44 (34%) patients with goitre, in 17/41 (41%) cases with GD and in 4/54 (7.4%) subjects in the control group (P<0.05, controls vs all patients with thyroid disease). Among cancer patients without metastatic disease, RT-PCR results correlated positively with lymph node status (P=0.05), grading (P=0.01) and elevated serum thyroglobulin levels (P=0.03). This is the largest study investigating the use of the TPO-RT-PCR assay. Positivity in TPO-RT-PCR correlates significantly with metastatic disease in cancer patients and with the presence of thyroid disease in general. To date, TPO-RT-PCR cannot substitute for standard techniques in the diagnosis of local recurrence or metastatic spread in thyroid cancer patients. However, as results of TPO-RT-PCR correlate significantly with lymph node status, grading and serum TG measurements in patients with non-metastatic disease, TPO seems to be an interesting molecular marker to look at in follow-up studies.

New interstitial HDR brachytherapy technique for prostate cancer: CT based 3D planning after transrectal implantation.

We have developed a new interstitial HDR brachytherapy technique for the treatment of prostate cancer using CT based 3D planning after transrectal implantation of four non-parallel needles. CT based needle reconstruction, target definition, evaluation and documentation, including DVHs and 3D imaging, is a feasible, safe and well tolerated treatment concept.

Influence of tumor biological factors on tumor cell dissemination in primary breast cancer.

BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of breast cancer patients is associated with poor prognosis and may therefore be related to aggressive breast cancer as indicated by tumor biological and clinicopathological factors. The aim of this study was to identify those features of the primary tumor related to the presence of disseminated tumor cells in the BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients were analyzed. Tumor biological features of the primary tumor including HER2, p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade, were studied for their association with BM involvement by univariate and multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary breast cancer patients had disseminated tumor cells in the BM. p53 expression, hormone receptor status, HER2 and Ki-67 were significantly related to BM involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95% CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 - 2.2) were the only independent determinants for BM involvement. CONCLUSION: The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.

Changes of serum HER2 status during clinical course of metastatic breast cancer patients.

BACKGROUND: Serum HER2 testing allows the determination of the real-time HER2 status of breast cancer patients. The aim of this investigation was to study (i) whether changes of serum HER2 status occur during the clinical course of breast cancer and (ii) to evaluate the prognostic significance of serum HER2 status, at the time of first diagnosis of primary breast cancer and at the onset of metastatic disease, for survival after relapse (SAR). MATERIALS AND METHODS: HER2 serum levels were retrospectively measured in 152 breast cancer patients at the time of first diagnosis of breast cancer and at the onset of metastatic disease by enzyme immunoassay. RESULTS: Twenty-seven out of 152 (18%) patients had elevated HER2 serum levels at the time of first diagnosis of breast cancer. In contrast, 56 out of 152 (37%) patients showed elevated serum HER2 levels when metastases were diagnosed. A change of serum HER2 status during clinical course was observed in 43 out of 152 (28%) patients. Serum HER2 status at the time of first diagnosis of breast cancer had no impact on survival after relapse (SAR) (p = 0.4). However, the median SAR for serum HER2-positive patients at the onset of metastatic disease was significantly shorter (8 months, 95% CI: 3-12) compared to patients serum HER2-negative at this time (18 months, 95% CI: 14-22) (p < 0.01). CONCLUSION: Serum HER2 status can change during the course of disease. Therefore, the serum HER2 status should be re-evaluated at the time of diagnosis of metastatic disease to optimize treatment decisions.

Spectrum of mammographically detected breast cancers.

Mammographic screening of women at both ends of the age spectrum presents a number of challenges. The purpose of this study was to characterize experience with mammographic detection of breast cancer. The two goals were 1) to establish the cancer detection rate of screening mammography and 2) to compare the tumor size of cancers found by mammography, physical examination, or both modalities. From January 1994 through June 1997, data on 609 consecutive female primary breast cancer patients were collected concurrent with definitive surgical therapy. The method of detection was determined by the surgeon, after reviewing mammogram and physical examination. Screening ultrasound was not used. For the 184 patients under 50 years of age, 53 (29%) cancers were detected by mammography only and 48 (26%) by physical examination only. Women under 50 years of age had fewer cancers detected by mammography only (P < 0.001) and more cancers detected by physical examination only (P = 0.0014) than those over 50. With increasing age, the proportion of women with ductal carcinoma in situ decreased (P = 0.004), and the proportion with T1c or T2 tumors increased (P = 0.006). We conclude that 1) when examining women under 50 years of age, the surgeon must be clearly focused on the double-edged sword of screening mammography in this age group, and 2) community cancer programs should encourage annual screening of women over 40 years of age but focus on those over 70, without an arbitrary upper age limit.

A multicenter survey of complications associated with 21,676 operative hysteroscopies.

OBJECTIVE: The following study analyses the hysteroscopic experience of multiple gynecologic centers throughout Germany in regard to the incidence of complications, the therapy of these complications and anesthesiological management during 21,676 hysteroscopic procedures. METHODS AND MATERIAL: Under the supervision of the German Society of Gynecology Endoscopy, 92 hysteroscopic centers were evaluated and the following information was collected: hysteroscopic experience in years, number of surgical hysteroscopies per year, total number of operative hysteroscopies, types of hysteroscopic procedures, intra- and post-operative complications. RESULTS AND CONCLUSION: The results of the study show that in most German centers, hysteroscopy is just being established. Nevertheless, the rate of complications such as perforation of the uterus, fluid-overload syndrome, infection and perioperative bleeding is small. This may be due to the high proportion of documented procedures performed by the more experienced centers.

Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer.

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m(-2), cisplatin 60 mg m(-2) on day 1 and capecitabine 1000 mg m(-2) daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43-82), disease stabilisation of 25% (95% CI: 11-47) and a disease control rate (CR + PR + SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.

The critical path method to analyze and modify OR-workflow: integration of an image documentation system.

Intraoperative image documentation is becoming more and more important for quality management in medicine, in terms of forensic documentation, research and teaching. Up to now, no software-based OR-image-documentation system fits satisfactorily into an OR-workflow. The objective of this study is to transparently show system integration in a clinical workflow for evaluating demands on future system developments. An example of the OR-workflow is presented for the department of obstetrics and gynecology at the University of Tuebingen (Germany). Twelve representative gynecologic laparoscopic surgeries were analyzed by using the critical path method (CPM). CPM network diagrams are shown for an actual laparoscopic workflow and for a workflow including an OR-image-documentation system. With the objective not to increase the total time of actual workflow, the maximum system operation time can be calculated for each period of time. Before surgery the maximum system operation time is x(max) = 7,3 minutes. After surgery it has to be assumed that system operation will increase total workflow time. Using the CPM to analyze requirements for system integration in a medical workflow has not yet been investigated. It is an appropriate method to transparently show integration possibilities and to define workflow-based requirements for the development process of new systems.

Strukturdifferenzierungen in Y-chromosom von Drosophila hydei: the unique morphology of the Y chromosomal lampbrush loops Threads results from 'coaxial shells' formed by different satellite-specific subregions within megabase-sized transcripts.

The results of pulsed-field gel electrophoresis (PFGE) analysis and two-colour transcript fluorescence in situ hybridization (FISH) for the three Threads-specific DNA satellites YLII, YLI and rally are in support of long-range clustering of these sequence families within the subterminal region on the long arm of the Y chromosome of Drosophila hydei. On the basis of the linear arrangement of at least four extended clusters of satellite-specific sequences, the loop morphology of wild-type and several mutant Threads can be explained by assumption of a single Threads-specific transcription unit comprising about 5.1 Mb of repetitive DNA located between the Pseudonucleolus and the Nucleolus organizer. Transcription is unidirectional from the Pseudonucleolus towards the terminally located Nucleolus organizer. Transcripts most likely start in front of or within the 3.2 Mb region of YLII-related sequences, pass through subsequent blocks of 1.2 and 0.3 Mb of YLI- and rally-related sequences, respectively, and cease within the region of a smaller block of YLI-related repeats. The megabase-sized transcripts remain physically linked to the DNA axis and their extended satellite-specific regions form coaxial clouds or shells around the central DNA axis. In this way each cluster of earlier-transcribed sequences generates a cloud or shell on top of the later-transcribed ones. According to this model of 'satellite-specific coaxial shells' the tube-like morphology and other peculiarities of the Y chromosomal lampbrush loops Threads can be explained as a result of satellite-specific RNA superstructures and/or formation of extended ribonucleoprotein (RNP) complexes between clusters of satellite-specific transcripts and specific proteins. On the basis of this model the specific morphology of several Threads mutants can be interpreted as the result of large interstitial or terminal deletions that alter the total length of the Threads-specific transcription unit without exerting other major effects on principal features of the transcription process along the Threads.

Molecular aspects of intron evolution in dynein encoding mega-genes on the heterochromatic Y chromosome of Drosophila sp.

Fertility genes on the heterochromatic Y chromosome of various Drosophila species are unique for several reasons. Most of them are megabase-sized. Their expression is restricted to premeiotic spermatocytes and often associated with unfolding of huge species-specific lampbrush loops. Molecular analysis of the orthologous dynein genes Dhc-Yh3, DhDhc7(Y) and DeDhc7(Y) on the Y chromosome of the three species D. melanogaster, D. hydei and D. eohydei, respectively, revealed that the megabase gene size as well as the species-specific morphology of the corresponding lampbrush loops kl-5, Threads and diffuse loops result from huge introns and their specific sequence composition, whereas the majority of all 20 introns in each of the three genes is in a size of 45-72 bp. The loop-specifying introns are extreme exceptions due to extended assemblies of degenerated transposable elements and/or large clusters of satellite DNAs. Here we use sequence information from the complete intron sets of three orthologous Y chromosomal dynein genes to deduce a scenario for an evolutionary pathway leading to the megabase-sized genes on the heterochromatic Y chromosome of Drosophila. The obvious bias between very small and species-specific mega introns is explained as the result of an autocatalytic mode of intron growth. An initial coincidental hit by a single transposable element extends the size of a 50 bp intron for about two orders of magnitude and determines it for preferential extension by similar insertion events. This phase of continuous moderate growth is followed by rapid size enlargements by repeating amplifications generating extended clusters of satellite DNA. Size control by recombination, on the other hand, is suppressed in Drosophila males by achiasmatic meiosis.

Multifibre Application in Laser-Induced Interstitial Thermotherapy under On-Line MR Control.

.The application of multiple fibres for the conformal irradiation of tumours by laser-induced interstitial thermotherapy (LITT) has been investigated. A study was performed to evaluate the coagulated zones produced in porcine muscle tissue in vitro. For delivering specified powers into the tissue, a multifibre system was developed which allows the simultaneous use of up to four fibres. A new quantitative method of magnetic resonance imaging (MRI) has been applied for real-time thermometry. It is based on the temperature dependence of the T1 relaxation time and the equilibrium magnetisation. The MR results were compared with the measurements of fibreoptic thermometers. Since the acquisition time of the selected MR sequence takes only 3 s per slice and the calculation of the temperature measurement could be realised within a few seconds, the temperature mapping works closely to real time. The accuracy of the temperature measurements in muscle tissue was 1.5°C. Whereas single-fibre applications induced convex-shaped isotherms, concave structures were generated by a multifibre LITT.

[Audiovisual telecommunication by multimedia technology in HNO medicine. ISDN--internet--ATM]. / Audiovisuelle Telekommunikation durch Multimediatechnologien in der HNO-Heilkunde. ISDN--Internet--ATM.

Telemedicine includes all medical activities in diagnosis, therapeutics, or social medicine undertaken by means of an electronic transfer medium, enabling the transmission of visual and acoustic information over long distances to doctors not personally present at the place of the requested consultation. Most experience with telemedicine applications has been gained in the field of diagnosis (teleconsultation, teleradiology, telepathology) and is expanding to quality control and quality assurance. Decisive for each form of application is its availability, practicability, cost, safety, and especially quality of audiovisual transmission. For telesurgical applications, particularly the use of minimally invasive techniques in otorhinolaryngology, head, and neck surgery, the high quality transmission of audiovisual data in real time is necessary. Rapid expansion and further developments in transmission technologies and networks in the last decade have created several technologies with increased quality and costs. In this paper, we tested different transmission media for audiovisual telecommunication--integrated services digital network (ISDN), Internet, and asynchronous transfer mode (ATM)--using real time video transmission of typical operations in otorhinolaryngology. Their applications, costs, and future perspectives are discussed.

Treatment of the twin-twin transfusion syndrome: initial experience using laser-induced interstitial thermotherapy.

This paper describes our initial experience with laser-induced interstitial thermotherapy (LITT) for the treatment of the twin-twin transfusion syndrome (TTTS). This procedure was utilized in four pregnancies-three monochorionic twin pregnancies and one triplet pregnancy (20-26 weeks of gestation)-with severe TTTS with fetal dropsy, polyhydramnion of the acceptor, and anhydramnion of the donor. In vitro examinations of placental tissue had shown that laser coagulation can be monitored by sonography, hence we used this method for the first time in these four pregnancies. Blood vessels connecting the two umbilical cords were determined prior to the treatment using a new ultrasound color technique which is highly sensitive and capable of representing slow blood flow velocities. A 1.2 mm thick puncture needle was then directed to the shunt under on-line ultrasound control. All patients had an anterior wall placenta. The laser fiber was inserted via this thin needle. A coagulation time of 2-3 min was necessary at 3 W. In the one twin pregnancy the intrauterine fetal death of the smaller child occurred 10 weeks after LITT, the other child survived and is healthy. A cesarian section was necessary in another twin pregnancy 1 week after LITT due to the intrauterine death of the smaller child. In the third twin pregnancy, the donor, who had already had distinct bradycardia prior to the treatment, died immediately after LITT. The intrauterine fetal death of the donor in the triplet pregnancy occurred 3 days after LITT once the volume of amniotic fluid had basically returned to normal. The tragic intrauterine death of the uninvolved child occurred 13 weeks later as a result of umbilical cord strangulation, the surviving child is healthy. All four pregnancies were severe and advanced cases of TTTS with a very poor prognosis, leaving us with no other alternative to the described method of treatment. The instruments we used are a lot thinner than those utilized for fetoscopic laser treatment to date. Furthermore, it is not necessary to penetrate the amniotic sac in patients with an anterior wall placenta; intraplacental vessels can be coagulated, and the laser energy required for LITT is also much lower. In our opinion these advantages justify the utilization of LITT under more promising conditions than those described above.