The role of the vaginal microbiome in gynaecological cancer.

Human microbiome research has shown commensal bacteria to be a major factor in both wellness and disease pathogenesis. Interest in the microbiome has recently expanded beyond the gut to include a multitude of other organ systems for which the microbiome may have health implications. Here, we review the role of the vaginal microbiome in health and disease, with a particular focus on gynaecologic malignancies. Further, we suggest that it may be possible to expand the use of probiotics in the treatment of gynaecological cancers. TWEETABLE ABSTRACT: A review of the research to date on the relation between the vaginal microbiome and gynaecological cancers.

Adaptations to water stress and pastoralism in the Turkana of northwest Kenya.

The Turkana people inhabit arid regions of east Africa-where temperatures are high and water is scarce-and they practice subsistence pastoralism, such that their diet is primarily composed of animal products. Working with Turkana communities, we sequenced 367 genomes and identified 8 regions putatively involved in adaptation to water stress and pastoralism. One of these regions includes a putative enhancer for STC1-a kidney-expressed gene involved in the response to dehydration and the metabolism of purine-rich foods such as red meat. We show that STC1 is induced by antidiuretic hormone in humans, is associated with urea levels in the Turkana themselves, and is under strong selection in this population (s∼0.041). This work highlights that partnerships with subsistence-level groups can lead to new models of human physiology with biomedical relevance.

The use of N-terminal pro-B type natriuretic peptide in a pre-operative setting to predict left ventricular systolic dysfunction on echocardiogram.

Heart failure is a major risk factor for adverse postoperative events following non-cardiac surgery. The use of transthoracic echocardiogram as a pre-operative investigation to assess cardiac dysfunction has limitations in this setting. The N-Terminal fragment of B-Type natriuretic peptide (NT proBNP) has been used in screening for heart failure. We have investigated the use of NT proBNP as a screening tool for left ventricular systolic dysfunction to reduce the requirement for pre-operative echocardiograms. Ninety-eight pre-operative non-cardiac surgical patients scheduled to undergo echocardiography were assessed clinically and with an NT proBNP measurement. Echocardiogram was used to define two groups of patients depending on the presence or absence of abnormal left ventricular function and the NT proBNP level was compared between the groups using non-parametric and receiver-operator-characteristic (ROC) curve analysis. In terms of pre-operative screening, a NT proBNP of <38.2 pmol x l(-1) had a 100% negative predictive value in predicting patients with normal left ventricular systolic function and would have prevented the requirement for echocardiogram in 43% of pre-operative patients. NT proBNP was superior to electrocardiological and clinical criteria for detection of a normal echocardiogram. This may have significant impact in the pre-operative assessment of patients undergoing non-cardiac surgery.

Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography.

PURPOSE: Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS: Thirty-four breast cancer patients were prospectively examined using F-18-PET and conventional BS. F-18-PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca(2+), alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methods was used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS: With F-18-PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18-PET imaging, clinical management was changed in four patients (11.7%). For F-18-PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P <.05) and 1.00 on a patient basis (for BS, it was 0.82; P <.05). CONCLUSION: F-18-PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.

CT planning of boost irradiation in radiotherapy of breast cancer after conservative surgery.

BACKGROUND AND PURPOSE: A study was performed to compare the accuracy of clinical treatment set-up and CT planning of boost irradiation in radiotherapy of breast cancer. MATERIAL AND METHODS: Between September 1993 and October 1994, 45 women who underwent breast conserving surgery and irradiation containing a boost to the tumour bed were investigated. Prospective evaluation of CT planning of the boost was carried out. The target volume/boost field, electron energy and treatment set-up had been defined on the basis of clinical examination, initial and postsurgical mammograms by one radiotherapist. Next, a planning CT was performed in treatment position and a CT-based treatment plan was calculated according to a target volume defined by another radiotherapist. The clinical treatment set-up was imported into our computer planning system and the resulting isodose plots were compared with those from CT planning and reviewed critically. RESULTS: The clinically defined treatment set-up had to be modified in 80% of the patients. Most discrepancies observed were related to the size of the boost field itself and the chosen electron energy. Minor changes had to be made with respect to angle of table and gantry. CONCLUSIONS: Critical review of the isodose plots from both methods showed clear advantages for CT planning. Guidelines for target definition in CT planning of boost irradiation and subgroups of patients benefiting from this technique are described.

Fabrication, characterization and fracture study of a machinable hydroxyapatite ceramic.

In this study the preparation of a machinable hydroxyapatite from mixtures of a fine, submicrometer powder and either a coarse powder composed of porous aggregates up to 50 microns or a medium powder composed of dense particles of 3 microns median size is described. These were characterized using X-ray diffraction, transmission and scanning electron microscopy and infra-red spectroscopy. Test-pieces were formed by powder pressing and slip casting mixtures of various combinations of the fine, medium and coarse powders. The fired test-pieces were subjected to measurements of firing shrinkage, porosity, bulk density, tensile strength and fracture toughness. The microstructure and composition were examined using scanning electron microscopy and X-ray diffraction. For both processing methods, a uniform interconnected microporous structure was produced of a high-purity hydroxyapatite. The maximum tensile strength and fracture toughness that could be attained while retaining machinability were 37 MPa and 0.8 MPa m1/2 respectively.

Fotemustine given simultaneously with total brain irradiation in multiple brain metastases of malignant melanoma: report on a pilot study.

Melanoma patients with multiple brain metastases not amenable to surgery or stereotactic radiotherapy were treated with total brain irradiation in fractions of 2.5 Gy four times weekly, up to 40 Gy. At days 1, 8, and 25100 mg/m2 fotemustine was infused 4 h before irradiation. Of 12 evaluable patients, four showed partial remission and three stabilization in the brain. The median survival in these two groups of patients was 6 months; the survival of the other patients was 2 months. Severe haematological side effects were observed in 6/13 patients. In conclusion, the combination of fotemustine and total brain irradiation seems to be more effective than either treatment alone, but bears the risk of additional bone-marrow toxicity.

Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer.

UNLABELLED: In a pilot trial we investigated whether significant differences in prostate cancer (PCA) imaging would be observed using [(11)C]acetate and [(11)C]choline positron emission tomography (PET). METHODS: Twelve patients were studied with both radiotracers. Whole body PET without attenuation correction was performed after injection of 0.95 +/- 0.15 GBq [(11)C]acetate and 0.84 +/- 0.13 GBq [(11)C]choline, respectively, from 5 to 60 min p. i. Focally increased uptake in bone, below the urinary bladder or in a lymph node region was considered as tumour. Primary tumour, lymph node involvement, bone metastases, local recurrence; and no evidence of disease were known in 2, 4, 2, 2; and 2 patients, respectively. RESULTS: [(11)C]Acetate uptake was highest in spleen and pancreas while [(11)C]choline uptake was predominant in liver and kidney parenchyma. However, interindividual variation was high. The potential of both radiotracers to detect known bone lesions, lymph node metastases, and imaging of the primary tumour was identical. However, both failed to detect a small local recurrence in two patients as well as to demonstrate lymph node involvement in one patient, which was confirmed by surgery. CONCLUSIONS: In this preliminary study, uptake of both radiotracers in prostate cancer or its metastases was nearly identical and none of them should be favoured. At present, both radiotracers influence patient management by detection of local recurrence, lymph node, or bone metastases of PCA.

The strength of dental ceramics.

Considerable changes have taken place in the range of ceramic materials available for dental use. Although the appearance of dental porcelain is good and biocompatibility excellent, its mechanical properties are somewhat limited. As a consequence, a number of distinct developments have taken place primarily to achieve greater strength; other goals having been to improve accuracy and simplification of production procedure. Progress has been made, but at the present time newer ceramics must still be regarded as complementary to established porcelains.

[Prostatectomy, brachytherapy, percutaneous irradiation. Which method helps your patients the most?]. / Prostatektomie, Brachytherapie, perkutane Bestrahlung. Welches Verfahren hilft Ihrem Patienten am besten?

For the treatment of cancer of the prostate that has not yet metastasized, several therapeutic options that promise lasting local tumour control are now available: Among the surgical options, radical retropubic prostatectomy is most commonly employed. The basic radiotherapeutic options are interstitial and external beam irradiation, or a combination of the two. The choice of the most suitable therapeutic approach is determined by the extent of the tumor, and the side effects that are acceptable to the patient.

[Subcranial resection of malignant tumors infiltrating the anterior skull base]. / Subkranialer Zugang bei Malignomen mit Beteiligung der Frontobasis.

BACKGROUND: Survival and quality of life after subcranial resection of malignant tumors infiltrating the anterior skull base should be evaluated. METHODS: Data were acquired retrospectively from patient charts and by telephone interview. Quality of life was assessed with the EORTC QLQ30 and H&N35 modules. RESULTS: From 1996 to 2004, 19 patients (mean age 52 years, 4 woman, 15 men) were surgically treated via a subcranial approach. Fifteen patients suffered from advanced carcinoma, 3 from advanced esthesioneuroblastoma, and 1 patient had a fibrosarcoma. Fifteen patients received adjuvant radiotherapy. During the mean follow-up period of 44 months (12-109 months), 6 patients died, 1 unrelated to the tumor. The probability to survive 5 years was 50 %, the mean survival time was 72 months. Anosmia was reported by 18 of 19 patients. A tension pneumocephalus was observed in 2 patients, one with lethal outcome, decreased vision in 1 patient, loss of vision in 1, persisting diplopia in 1, deep wound infections in 2, and CSF leak in 2 patients. Quality of life was assessed on the average 36 months following end of therapy and did not differ substantially from other patients with head-neck malignancies. CONCLUSION: Most, malignant tumors infiltrating the anterior skull base can be treated curatively. The treatment outcome is well comparable to other head and neck tumors of corresponding stage.

Porous ceramic lamellae for orthodontic ceramic brackets: part II: in vitro performance testing.

This study was undertaken to test a new and original orthodontic bracket base, consisting of a porous lamella, which was designed to facilitate removal of ceramic brackets from the enamel surface after treatment. In the phase of the study presented here, two types of lamella and the adhesive resin used to bond them to brackets and teeth, were evaluated in vitro. Two types of test were carried out on bracketed teeth. The tensile bond strength was measured for specimens that had been either kept in water for 24 h at 37 degrees C or subjected to 18000 cycles in water between 6 degrees C and 55 degrees C. The stress required to remove brackets with debracketing pliers was measured and the mode of failure recorded for specimens that had been kept in water for 24 h at 37 degrees C. The results indicate that bracket/lamella assemblies can be bonded to enamel sufficiently strongly for clinical application and can be safely removed without damage to enamel.

Porous ceramic lamellae for orthodontic ceramic brackets: part I: fabrication and characterization.

This study was undertaken to test a new and original orthodontic bracket base, consisting of a porous lamella, which was designed to facilitate removal of ceramic brackets from the enamel surface after treatment. In the phase of the study presented here, porous pellets were made by bonding coarse alumina particles (calcined or fused) with mullite, formed by their reaction with fine quartz particles during firing of the mixture at 1700 degrees C. After machining the pellets to the desired shape, nine types of lamellae with different porosities were attached to the brackets using two different adhesive resins, and also bonded to bovine enamel using the same adhesives. The tensile bond strengths for the assemblies were determined so that the lamellae and the bonding adhesive that might be suitable for clinical application could be selected for testing in vitro in the second phase of the study.

Antithyroid drug treatment of Graves' disease in pregnancy: long-term effects on somatic growth, intellectual development and thyroid function of the offspring.

With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.

Experimental analysis of factors affecting metastatic spread using naturally occurring tumours.

This paper describes the applications and latest results of recently developed techniques in metastasis research using naturally occurring animal and human tumours. Intravenous inoculation of cells from murine mammary tumours into syngeneic recipients has shown that some are consistently capable of heavy pulmonary colonisation (HCP) while others have low colonisation potential (LCP). These distinct characteristics are stable over wide cell-dose ranges. Autopsies on a sample of 100 consecutive tumour-bearing C3H/Avy mice revealed that the incidence of spontaneous metastasis is 26%. When inoculated intravenously, cells from some of the spontaneously metastatic primary tumours had HCP and others LCP. We now report that, knowing the degree of pulmonary colonisation of a particular tumour after intravenous inoculation, the degree of its spontaneous metastasis in the original host, and the dose-response relationships mentioned above, it is possible to back-titrate the degree of cell shedding from the tumour into the blood stream. Other experiments reported here demonstrate that separate mammary tumours on the same animal have independent colonisation potentials and growth rates, that tumours appearing later on an animal are not necessarily more capable of metastatic spread than the earlier ones, and that tumour weight and length of presence on the host do not show any strong correlation with spontaneous metastatic spread. A moderately significant association between pulmonary colonisation potential and tumour growth rate is reported and evidence corroborating our earlier observations that ability to colonise the lungs is possessed only by neoplastic mammary cells is also presented. Similar investigation are, of course, much more difficult to organise on tumour spread in man because of ethical and logistic considerations but it is possible to circumvent some of these difficulties and we refer to some of our ongoing studies.

[Systematic analysis of local growth behavior and cervical lymph node metastasis of nasopharyngeal carcinoma--a clinical and computerized tomography examination]. / Systematische Analyse des lokalen Wachstumsverhaltens und der zervikalen Lymphknotenmetastasierung von Nasopharynxkarzinomen--eine klinisch- computertomographische Untersuchung.

BACKGROUND: Assessment of the incidence and patterns of cervical lymph node involvement according to the location, extension, and histological subtype of nasopharyngeal carcinoma. PATIENTS AND METHODS: The findings of the clinical and CT examinations of 80 patients with histological evidence of nasopharyngeal carcinoma (9T1-, 20 T2-, 17 T3-, 34 T4-carcinomas, lymph node involvement in 59 cases) were evaluated retrospectively. The histological subtype, local tumor spread, relation of the primary to the parapharyngeal fascias, compartments, and skull base structures were analysed and related to the cervical lymph node involvement. RESULTS: Two main types of nasopharyngeal carcinomas with different patterns of cervical lymph node involvement were identified: the posterior wall type, which spreads into the retropharyngeal and spinal accessorial neck node chains and the ventral type, which is located which is located at the roof, anterior, and lateral walls of the nasopharynx and spreads into the jugular neck node chains, preferring the neck side in which the main part of the primary is located. The border of lymph drainage via retropharyngeal-spinal accessorial or via jugular neck node chains is localised ventral of the origin of the m. capitus longus at the skull base. If the primary involves the prestyloidal compartment, the tumor may spread into the ipsilateral submaxillary lymph nodes. Combinations of the different types are frequently found with the neck node spread following the described directions. CONCLUSIONS: Knowledge of the regular patterns of spread of nasopharyngeal carcinoma is important for treatment procedures, especially for planning 3-dimensional radiotherapy.

Surgery, radio- and chemotherapy for multimodal treatment of rectal cancer.

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. The addition of RT to adjuvant CT reduces local relapses without significant impact on survival (NSABP R-02). Vice versa, the addition of CT to RT or an improved CT in the RCT-concept prolongs survival. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 9 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT reduced local relapse rates in addition to total mesorectal excision (TME) but did not extend survival. The preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. Phase III data justifying its routine use in all UICC II + III stages are not yet available. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Preoperative RCT (or RT) may evolve as standard, if the patient selection is improved and postoperative morbidity and long term toxicity reduced. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT at the same indications. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality in adjunction to surgery. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT. In the future, multimodal treatment of rectal cancer might be more effective, if individualized according to prognostic factors.

Initial results in the assessment of multiple myeloma using 18F-FDG PET.

This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three patients with known multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The results of routinely performed radiographs and of scans obtained using all available imaging modalities (MRI, CT), as well as the clinical course, were used for verification of detected lesions. Focally increased tracer uptake was observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23 patients. In addition, 71 further bone lesions which were negative on radiographs were detected in 14 patients. Twenty-six (36.6%) of these lesions could be confirmed in ten patients. As a result of FDG-PET imaging, clinical management was influenced in five (14.0%) patients. The positive predictive value for active disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG uptake and 75% in patients with diffuse bone marrow uptake. Depending on the interpretation of the PET scans in patients with diffuse bone marrow uptake, the sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%. FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients who had osteolytic bone lesions. FDG-PET might contribute to the initial staging of solitary plasmacytoma.