MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.

Overview and evaluation of the value of fine needle aspiration cytology in determining the histogenesis of liver nodules: 14 years of experience at Hannover Medical School.

Fine needle aspiration (FNA) is a sensitive and specific method (95%), often helpful in characterizing suspected liver lesions. It is appropriate to distinguish between primary and secondary liver neoplasia. Moreover, in most cases, the use of cell block preparations of small specimens allows immunocytochemical evaluation to determine the nature of the primary tumour. In a retrospective study at Hannover Medical School (MHH) from 1998 to 2012 (14 years), 4,136 sonographically guided FNAs were performed. The patients provided consent and the study protocol was approved by the local ethics committee. There were 39.6% malignant and 57.5% benign lesions in the liver, while 2.8% of the cases were undetermined. FNA was non-representative in 1.1% of the cases. The diagnostic utility of highly differentiated hepatocellular carcinoma (HCC; G1) remains difficult; cell bridges with cell atypia are pathognomonic for diagnosis. Ancillary techniques and immunocytochemical investigations will increase the sensitivity and specificity, particularly by using the cell block technique.

Extended surgery for advanced pancreatic endocrine tumours.

BACKGROUND: Pancreatic endocrine tumours are often diagnosed at an advanced stage with hepatic metastasis. This study investigated whether extended resections for advanced malignant pancreatic endocrine tumours influenced disease-free and disease-specific survival. METHODS: Patients who had curative resection of pancreatic endocrine tumours were analysed retrospectively for disease-free and disease-specific survival, with a focus on the role of extended surgical resection. RESULTS: Forty-one patients were included in the analysis, 13 of whom underwent extended surgical resection in addition to pancreatic resection. This included partial liver resection in nine patients, portal vein resection in three, partial gastric resection in five and liver transplantation in three patients. There were no deaths in hospital or within 30 days. Median follow-up was 40 (range 2-239) months. Thirty-five, 24 and 13 patients survived more than 1, 3 and 5 years respectively. Patients who underwent extended resection had similar disease-specific survival to those who had pancreatic resection alone (hazard ratio (HR) 1·50, 95 per cent confidence interval (c.i.) 0·35 to 6·35; P = 0·581) but with a higher frequency of complications (odds ratio (OR) 4·28, 95 per cent c.i. 1·04 to 17·62; P = 0·044). Among patients with liver metastases, the mortality rate was higher in those in whom liver resection was not possible than in patients who had liver resection (HR 9·24, 1·00 to 85·18; P = 0·049). Patients who had liver resection had similar disease-specific survival to those without liver metastases (HR 0·84, 0·09 to 7·57; P = 0·877). CONCLUSION: Extended surgical resection for locally advanced and metastatic pancreatic endocrine tumours is feasible with encouraging disease-specific survival.

Detection of high risk HPV and Chlamydia trachomatis in vaginal and cervical samples collected with flocked nylon and wrapped rayon dual swabs transported in dry tubes.

A dual collection device containing flocked and wrapped rayon swabs was used to collect vaginal and cervical samples from 494 women. The swabs were separated into individual tubes and sent to the laboratory in a dry state, where they were hydrated and tested for high risk HPV DNA [Digene-Qiagen hybrid capture 2] and Chlamydia trachomatis using in-house real-time PCR. The flocked swabs identified more high risk HPV and C. trachomatis infections from both sampling sites.

[Development of early-summer meningoencephalitis (FSME) in the Thurgau region 1990-1995--a new endemic area?]. / Entwicklung der Frühsommer-Meningoenzephalitis (FSME) in der Region Thurgau 1990-1995--ein neues Endemiegebiet?

Tick-borne encephalitis (TBE) is a viral infection transmitted by bites of infected ticks. The clinical course is mostly mild, but death occurs in 1-2% of TBE infections and nearly half of patients with meningitis/meningoencephalitis show residual disease, above all chronic headache. TBE-infected ticks occur only in endemic areas. A knowledge of the endemic areas is very important for immunoprophylaxis of TBE. In recent years between 26 and 97 cases of TBE have occurred in Switzerland. The largest endemic areas are in Canton Schaffhausen, the northern part of Canton Zurich and the north-west of Canton Thurgau. Another endemic area is known in the region of Thun in Canton Berne. Another possible endemic area is known in the Zurich Oberland around Elgg, only 7 km from Aadorf in Thurgau. Up to now, Diessenhofen in the north-west of Thurgau was the only known possible endemic area. In 1994 and 1995 we observed an accumulation of TBE infections in western Thurgau. The question was whether there are other endemic areas in Thurgau. In this retrospective analysis we studied the TBE cases in Thurgau between 1990 and 1995 with data derived from the cantonal health authorities reports. Clinical data were taken from case histories of the two cantonal hospitals in Frauenfeld and Münsterlingen, completed by data from family doctors and patients. Between 1990 and 1995 30 TBE infections (1990; 1, 1991: 4, 1992: 3, 1993: 1, 1994: 4 certain, 3 uncertain, 1995: 14) were observed. TBE infections appeared between May and October (maximum in May). 14 patients remembered a bite by a tick several weeks before onset of the illness. 7 bites occurred in the area of Frauenfeld/Aadorf. Only one bite occurred in Diessenhofen. 2 patients were infected in well-known endemic areas in Canton Zurich, a vicinal region in the west of Thurgau. In 1995 the incidence of TBE in Thurgau was 5.4/100000 population. In 9 of the 14 patients recalling a bite by a tick (64.4%), the bites occurred near their domicile. No bite was seen east of a line between Steckborn and Weinfelden. The incidence of TBE in Thurgau in 1995 was clearly higher than the average in Switzerland in recent years (0.46/100000), and higher than in the well-known endemic areas in the vicinity (Schaffhausen 3.95, Zurich 1.31). Based on our data, the region Frauenfeld/Aadorf must be declared a new endemic area for TBE. Probably the well-known endemic area in the Zurich Oberland in the vicinity of Elgg has spread eastward. Persons who are often in the forests of this region should be advised to be vaccinated.

Manifestations of Chlamydia induced arthritis in patients with silent versus symptomatic urogenital chlamydial infection.

OBJECTIVES: To evaluate whether Chlamydia-infected patients with and without urogenital symptoms have similar rheumatological manifestations or whether they belong to distinct clinical groups. METHODS: In a university-based study, we examined patients with unexplained arthritis in whom other rheumatic diseases had been excluded for urogenital chlamydial infection, and we investigated the clinical and radiological manifestations of the Chlamydia-positive patients. RESULTS: Sixty of 283 patients (21%) with unexplained arthritis had urogenital chlamydial infection. The infection was asymptomatic in 30%. There was no difference in the pattern of arthritis or immunological and serological characteristics in the patients with and without symptoms of urogenital infection, respectively. CONCLUSION: The pattern of Chlamydia-induced arthritis is similar in patients with or without symptoms of urogenital chlamydial infection. To recognize CIA, it may be helpful to examine patients with unexplained arthritis for Chlamydia even though they do not have symptoms of urogenital infection.

Antibacterial activity of oral antibiotics against anaerobic bacteria.

The spectrum and the antibacterial susceptibility of anaerobic bacteria to oral antibiotics isolated from clinical specimens was assessed in two different centres, the first receiving specimens from University departments and the second from general practitioners and small hospitals. Susceptibility was studied with a microtiter ready-to-use panel system, using the manufacturer's modified Wilkins-Chalgren's broth as the test medium for the following antibiotics: ampicillin, ampicillin+sulbactam, amoxicillin+clavulanic acid, cephalexin, cefaclor, cefuroxime, cefetamet, clindamycin, doxycycline and erythromycin. Anaerobic bacteria frequently encountered in clinical specimens from the University departments were mainly resistant Bacteroides spp., especially Bacteroides fragilis, Propionibacterium spp. and Peptostreptococcus spp., whereas in the outpatient center, Peptostreptococcus spp, Actinomyces spp. and Veillonella parvula (usually considered as colonizing flora) represented 90% of the cultured bacteria. The study shows that the members of most Bacteroides spp. encountered in a hospital environment are resistant to most of these agents (except clindamycin, amoxicillin+clavulanic acid, and ampicillin+sulbactam), whereas the gram-positive pathogens are widely covered by most of the orally available agents studied including cefetamet.

Detection of tick-borne encephalitis (TBE) virus in Liechtenstein.

In this study, we present the first detection of a focus of tick-borne encephalitis (TBE) virus-infected ticks in Liechtenstein. The focus is located on a much-used forest path near Vaduz, the capital of the principality. The virus isolated is a representative of the Western subtype of the TBE virus. It is thus closely related to or identical with the other strains isolated in western Europe.

New techniques in rapid viral diagnosis.

The development of new diagnostic techniques in immunology and molecular biology during the last two decades has opened up new possibilities for rapid viral diagnosis. Solid phase immunoassays for antigen and antibody detection are now widely used in diagnostic settings. Several novel techniques have been introduced and have led to commercially available tests. Diagnostic methods using nucleic acid amplification procedures are already applied in research laboratories and will be commercialized soon. Biosensor-based diagnostic techniques have the potential of generating a result nearly instantaneously and it has become possible to monitor kinetic processes. Automatization and simplified procedures are needed to allow diagnostic tests to be performed soon after the sample has been obtained from the patient. In order to evaluate the new procedures and avoid false results, rigorous quality control in diagnostic virology will have to be instituted.

[Endangering of the Liechtenstein population by the early-summer meningoencephalitis virus]. / Gefährdung der Bevölkerung in Liechtenstein durch das Virus der Frühsommer-Meningoenzephalitis (FSME).

There have been a few severe cases of tick-borne encephalitis in Liechtenstein during the last 20 years. To form a better idea of the risk of infection and the potential benefit of vaccination, a total of 311 sera from different cohorts were investigated for antibodies to tick-borne encephalitis. The mean seroprevalence found was 3.6% and was not higher even in persons who were active in professional forestry. The antibodies measured derived in all groups mainly from previous vaccination and in only 2 cases (0.6%) from natural infection. It is concluded that the risk of TbE infection in Liechtenstein is very low. Therefore, a reduction in cases would probably be achieved only by mass vaccination.

[Classical pseudomembranous diphtheria caused by Corynebacterium ulcerans]. / Klassische pseudomembranöse Diphtherie durch Corynebacterium ulcerans.

In a 63-year-old patient presenting with signs of classical diphtheria including membranous pharyngotracheobronchitis and myocarditis, Corynebacterium ulcerans was isolated in pure culture from the membranes. The strain produced a toxin specific for C. ulcerans but no diphtheria toxin. The patient was discharged after a complicated hospital course including respiratory and cardiac failure. Besides Corynebacterium diphtheriae, which has very rarely been isolated in Switzerland in recent years, Corynebacterium ulcerans should be considered as a cause of classical diphtheria.

Intestinal cryptosporidiosis acquired from a cat.

A case of intestinal cryptosporidiosis in an eight-year-old boy is presented. The patient became ill during a visit to a farm where diarrhoea in newborn calves is a recurrent problem. Furthermore, on that farm kittens periodically suffer from diarrhoea and failure to thrive. Oocysts of Cryptosporidium sp. were identified in the stool of the patient, and in the stool of the cat he had contact with. At that time the calves were not infected. The patient's gastrointestinal symptomatology consisted of severe diarrhoea, vomiting, colics and moderate dehydration, and was preceded by coughing.

[Blastocystis hominis in feces. An assessment of 56 cases]. / Blastocystis hominis im Stuhl. Eine Auswertung von 56 Fällen.

Over a twelve-month period all 3918 stool samples sent to our institute were investigated for Blastocystis hominis. This protozoon was detected in 384 samples. The stools of 50 healthy controls were negative. In 56 positive cases detailed clinical information was obtained: 26 of these patients had diarrhea, while only extraintestinal symptoms had been recorded in 10 cases. Blood eosinophilia was observed in 8 patients. Of 16 specifically treated patients, 10 responded to therapy. Although the pathogenic significance of B. hominis is still unclear, we believe our observations justify antibiotic therapy in selected cases.

[Cultural and serologic Chlamydia detection in diagnosis of sterility and increased risk of infection]. / Kultureller und serologischer Chlamydien-Nachweis in der Sterilitätsdiagnostik und bei erhöhtem Infektionsrisiko.

364 women were studied for the possible role of chlamydia trachomatis infection as a factor related to infertility. C. trachomatis was isolated from the cervix in 20% of our high-risk STD patients and in a much lower proportion in patients with tubal (5%) or unexplained (4%) infertility. IgG-antibodies to C. trachomatis were found in 75% of patients with tubal infertility, in 44% of women without gynaecological diseases and in 87% of the high-risk STD patients. By contrast, the difference was significant in the IgA-antibody tests. 67% of the women with tubal infertility and only 25% of the women with nontubal infertility were positive. From these data it appears, that antecedent infections with C. trachomatis, as measured by antibody prevalence, are an important factor in infertility of tubal origin.

[Serologic studies in the diagnosis of pneumonia]. / Serologische Untersuchungen in der Diagnostik von Pneumonien.

The importance of serological determination procedures for the diagnosis of pathogens was investigated in 207 episodes of pneumonia. The pathogenic organisms were detected in 138 cases; in 40 cases serological analysis helped to establish the diagnosis, while in 11 cases of pneumonia, the diagnosis was possible only with serology. The organisms most commonly found by serological investigations were Cytomegalovirus (n = 10), Aspergillus fumigatus (n = 7), and the influenza B virus (n = 7). Multiple infections, usually triggered by bacterial pathogens, were found in 48% of the cases of pneumonia with serological evidence of pathogens. In 71 episodes of pneumonia, the patients were immunosuppressed; in 11 cases, the causative organism was detected serologically.

[Pneumonia in patients with and without immunosuppression--value of bronchoscopic biopsy technics for the detection of pathogens]. / Pneumonien bei Patienten mit und ohne Immunsuppression--Wertigkeit bronchoskopischer Entnahmetechniken zum Erregernachweis.

Bronchoscopic diagnosis was performed in 91 patients with 100 episodes of fresh pneumonia. In already existing immunosuppression (n = 51, Group A) pathogens were most frequently identified via bronchoalveolar lavage (70%); in patients without immunosuppression (n = 49, Group B) the identification quota in respect of the central bronchial secretion (53%) and bronchoalveolar lavage (47%) were comparable. In Group A the most frequently occurring pathogens were Pneumocysti carinii (n = 18) and Aspergillus fumigatus (n = 7), in Group B Streptococcus pneumoniae (n = 8) and Staphylococcus aureus (n = 7).

[Incidence, diagnosis and follow-up of bacterial pneumonia in AIDS]. / Häufigkeit, Diagnostik und Verlauf bakterieller Pneumonien bei AIDS.

In 36 patients suffering from AIDS (age: 21-62 years) the incidence, the efficiency of diagnostic procedures and the clinical course of bacterial pneumonias were analysed. 19 out of 20 episodes with bacterial pathogens were found in 18 patients via fibre-bronchoscopic sampling. The most frequently observe bacteria were S. pneumonia (n = 8), M. tuberculosis (n = 3) and atypical mycobacteria (n = 6). At least 2 pathogens of the pneumonia were observed in 9 episodes. An appropriate treatment with antibiotics on the basis of a proper microbiologic diagnosis was successful in 65% of the cases. Because of the unreliability of history, clinical findings, chest X-ray, and laboratory features, successful management of bacterial pneumonias of AIDS patients should be based on the knowledge of the causative agent which can be obtained by the efficient and safe procedure of bronchoscopic sampling.

[Pneumonia in AIDS: pathogen spectrum and diagnostic value of various fiberoptic bronchoscopy methods for the detection of pathogens]. / Pneumonien bei AIDS: Erregerspektrum und diagnostische Wertigkeit verschiedener fiberbronchoskopischer Methoden zum Erregernachweis.

39 fibre-bronchoscopic examinations were performed prospectively in 29 AIDS-patients with pneumonia. Specimens were obtained from the central bronchial system with a protected brush and by suction, from the infiltrated peripheral area by catheter suction, protected brush, bronchoalveolar lavage (BAL) and transbronchial biopsy in randomized order. In patients with non-bacterial pneumonia, pneumocystis carinii (n = 20) was the most frequent pathogen. In this group BAL had a significantly higher rate of pathogen detection than other techniques. In patients with bacterial pneumonia (n = 10) the pathogens were found in all cases by suction from the central bronchial system. Fibre-bronchoscopy in patients with AIDS and pneumonia should include specimens from the central bronchial system and a bronchoalveolar lavage.

[Clinical and serological characterization of Chlamydia-induced arthritis]. / Klinische und serologische Charakterisierung der Chlamydien-induzierten arthritis.

Chlamydia-induced arthritis was diagnosed in 32 patients (18 men and 14 women; mean age 33 [17-54] years). 13 were HLA-B27 positive. In 19 patients the arthritis was largely confined to one joint. Enthesopathies occurred in 14 patients, and in 13 sacroiliitis was diagnosed radiologically. The most frequent extra-articular changes affected the urogenital system (26 cases). The full Reiter syndrome was present in seven patients (four men, three women). All patients had serum antibodies against Chlamydia. In 16 patients Chlamydia was diagnosed as the causative organism by urogenital swab. Chlamydia-induced arthritis differs from other arthritides in the high proportion of HLA-B27 negative patients.