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.

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.

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.

[Significance and problems of Chlamydia detection in urologic patients]. / Bedeutung und Problematik des Chlamydiennachweises bei urologischen Patienten.

Chlamydiae represent the aetiological agent in non-gonococcal urethritis in about 50% of the cases, but it is also increasingly recognized that Chlamydia trachomatis can cause prostatitis or epididymitis. The introduction of methods for the direct detection of chlamydia in clinical materials allows early diagnosis and therefore effective antibiotic therapy. The new tests however give both false positive and false negative results.

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.

[Urogenital chlamydial infections: significance and diagnosis]. / Urogenitale Chlamydien-Infektionen: Bedeutung und Diagnostik.

Chlamydia are common agents of sexually transmitted diseases and in this country more frequent than Neisseria gonorrhoeae. Approximately 10% of all infections with chlamydia trachomatis are followed by complications, which can lead to infertility and other sequelae. Therefore, early recognition of the infection and subsequent effective therapy are important. The dermatologist is often the first physician consulted and the outcome of the infection may depend on his diagnostic and therapeutic measures. The experienced microbiologist can provide an etiologic diagnosis. For this, isolation of Chlamydia trachomatis in optimally performed tissue culture still is the most sensitive and specific method. Currently available commercial IF- and ELISA-tests for direct detection of the agent in secretions are less sensitive and less specific.

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.

[Development of resistance in imipenem therapy in Pseudomonas aeruginosa]. / Resistenzentwicklung unter Imipenem-Therapie bei Pseudomonas aeruginosa.

8.4% of the isolated Pseudomonas aeruginosa strains were resistant against imipenem in this study. 3.7% of them became resistant as a result of the antibiotic therapy. In some patients on intensive care units, the resistance of Pseudomonas aeruginosa against imipenem emerged within a few days. In two of these cases a simultaneous loss of activity of the other pseudomonas-beta-lactams was observed.

[Immunologic methods for the detection of diphtheria toxin (passive hemagglutination and ELISA for toxin detection in cultures and serum)]. / Immunologische Methoden zum Nachweis von Diphtherie-Toxin (Passive Haemagglutination und ELISA zum Toxinnachweis aus Kulturen und im Serum).

A competitive passive hemagglutination assay (cPHA) easy to perform and a highly sensitive ELISA have been investigated for detection of diphtheria toxin from cultures and from human serum. The sensitivity of the cPHA (8 ng toxin/ml) was high enough to detect toxin in pure cultures containing C. diphtheriae. For this application the cPHA proved to be a simple and reproducible alternative to the Elek-Ouchterlony test. Toxin in culture filtrates of nasal and tonsillar swabs containing toxinogenic strains of C. diphtheriae together with germs of the physiological flora and toxin in serum can be detected with the more sensitive Biotin/Streptavidin ELISA (0.6 ng toxin/ml). This allows the confirmation of the clinical diagnosis "diphtheria" within 24-48 h.

[Granulomatous cytomegalovirus hepatitis]. / Granulomatöse Zytomegalievirus-Hepatitis.

Four primarily healthy patients with granulomatous hepatitis during acute cytomegalovirus infection are described. Granulomatous hepatitis associated with cytomegalovirus infection has been described previously in only 7 patients. As the authors have observed 4 such cases within a period of one year, this disease pattern may occur more frequently than was formerly assumed.

[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.

[Blastocystis hominis, a parasitic cause of diarrhea]. / Blastocystis hominis, ein parasitärer Durchfallerreger.

The frequency of detection of Blastocystis hominis in the stools of patients with gastroenteritis is reported. Over a twelve-month period B. hominis was identified in the stools of 69 (4.72%) out of 1460 patients. Of these 69 positive samples, 45 (65%) contained B. hominis alone and in 24 (35%) it was present together with other parasites such as Lamblia intestinalis, Entamoeba histolytica, Entamoeba coli, Endolimax nana, Iodamoeba buetschlii, Ancylostoma duodenale, Ascaris lumbricoides, Trichuris trichiura, and Hymenolepis nana. In 19 of the 69 patients with B. hominis, the parasite was found only in small numbers but as the sole pathogen. It is still unclear whether B. hominis must be considered a pathogenic agent; the clinician should however be aware of this parasite as a possible cause of gastroenteritis, particularly when no other pathogen can be identified.

Comparison of buffalo green monkey cells and McCoy cells for isolation of Chlamydia trachomatis in a microtiter system.

A total of 1,229 urogenital samples of patients with sexually transmitted diseases and prostitutes were inoculated simultaneously in McCoy cells and Buffalo green monkey (BGM) cells by using a microtitration technique. BGM cells proved to be slightly more sensitive than McCoy cells, and they usually showed more and larger inclusions and were more resistant to cytotoxic substances in samples. The decrease in sensitivity as a result of mycoplasmal contamination was much more prominent in McCoy cells than in BGM cells.

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.

The preparation of a reference serum for the determination of IgG and IgM antibodies against cytomegalovirus and its evaluation in a collaborative trial.

It is now generally accepted that laboratory data produced by different laboratories using different techniques can be better compared if the results are related to a reference preparation. Even within one laboratory the use of a stable reference preparation helps to reduce the day to day variation of the results. Although this idea has been firmly established for many years the introduction of reference preparations so far has met only with limited success. One of the reasons for this development may be the lack of adequate preparation to be used for this purpose. Recently, diagnostic virology has introduced new serological methods in an effort to make a rapid diagnosis and to differentiate between acute and past infection by the determination of specific antibodies in the IgM, IgA or IgE fraction of the patient's serum. In such a situation, a reference IgM serum of low activity would help to differentiate between persistent or past and recent infection. It was therefore attempted to establish such a reference serum containing antibodies against CMV in the IgM fraction.

Differentiation of recent and past infections with Legionella pneumophila by determination of specific IgM.

The ELA-IgM antibody test as used in viral diseases can also be applied to infections with Legionella pneumophila and is yielding similar results as the IgM determination by immunofluorescence. Complement-fixation and microagglutination are yielding also positive results in IgM-positive sera. IgM antibodies appear relative late after beginning of the disease and are persisting for several months. There is evidence that IgM antibodies as detected by the use of a Legionella pneumophila antigen are also cross-reacting to a number of other antigens.

Epidemiology of diphtheria: polypeptide and restriction enzyme analysis in comparison with conventional phage typing.

Several methods for epidemiological typing of Corynebacterium diphtheriae were compared with the well accepted phage typing analysis. For this purpose, isolates from outbreaks of diphtheria in specific areas of the FRG and Sweden were analyzed by phage typing, their bacterial polypeptide profiles were examined and their phage-DNA restriction enzyme patterns were compared. All techniques were able to identify whether certain outbreaks were epidemiologically linked or not. Phage typing and phage-DNA restriction enzyme fragment analysis were limited in their application to lysogenic strains, whereas bacterial polypeptide analysis was universally applicable. Analysis of bacterial polypeptides was superior to all methods, especially in terms of speed and simplicity.

[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.

[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.