Transabdominal-pelvic-perineal (TAPP) anterolateral thigh flap: A new reconstructive technique for complex defects following extended abdominoperineal resection.

BACKGROUND: Abdominoperineal resection (APR) following radiotherapy is associated with a high rate of perineal wound complications. The anterolateral thigh (ALT) flap, combined with the vastus lateralis (VL) muscle, can cover complex perineal and pelvic anteroposterior defects. This is used for the first time transabdominally through the pelvis and the perineum (TAPP) in the infero-posterior directions; this technique has been described and illustrated in this study. METHODS: Among over 90 patients who underwent perineal reconstruction between May 2004 and June 2011, six patients presented high-grade tumours invading perineum, pelvis and sacrum, thereby resulting in a continuous anteroposterior defect. ALT + VL TAPP reconstructions were performed after extended APR and, subsequently, sacrectomy. Patients were examined retrospectively to determine demographics, operative time, complications (general and flap-related), time to complete healing and length of hospital stay. Long-term flap coverage, flap volume stability and functional and aesthetic outcomes were assessed. RESULTS: Mean operating time of the reconstruction was 290 min. No deaths occurred. One patient presented partial flap necrosis. Another patient presented a novel wound dehiscence after flap healing, due to secondary skin dissemination of the primary tumour. Following volumetric flap analysis on serial post-operative CT scans, no significant flap atrophy was observed. All flaps fully covered the defects. No late complications such as fistulas or perineal hernias occurred. Donor-site recovery was uneventful with no functional deficits. CONCLUSIONS: The use of the ALT + VL flap transabdominally is an innovative method to reconstruct exceptionally complex perineal and pelvic defects extending up to the lower back. This flap guarantees superior bulk, obliterating all pelvic dead space, with the fascia lata (FL) supporting the pelvic floor.

Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis.

BACKGROUND: For the past decade (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) have been used for the assessment of patients with brain tumor. However, direct comparison studies reported only limited numbers of patients. Our purpose was to compare the diagnostic performance of FET and FDG-PET. METHODS: We examined studies published between January 1995 and January 2015 in the PubMed database. To be included the study should: (i) use FET and FDG-PET for the assessment of patients with isolated brain lesion and (ii) use histology as the gold standard. Analysis was performed on a per patient basis. Study quality was assessed with STARD and QUADAS criteria. RESULTS: Five studies (119 patients) were included. For the diagnosis of brain tumor, FET-PET demonstrated a pooled sensitivity of 0.94 (95% CI: 0.79-0.98) and pooled specificity of 0.88 (95% CI: 0.37-0.99), with an area under the curve of 0.96 (95% CI: 0.94-0.97), a positive likelihood ratio (LR+) of 8.1 (95% CI: 0.8-80.6), and a negative likelihood ratio (LR-) of 0.07 (95% CI: 0.02-0.30), while FDG-PET demonstrated a sensitivity of 0.38 (95% CI: 0.27-0.50) and specificity of 0.86 (95% CI: 0.31-0.99), with an area under the curve of 0.40 (95% CI: 0.36-0.44), an LR+ of 2.7 (95% CI: 0.3-27.8), and an LR- of 0.72 (95% CI: 0.47-1.11). Target-to-background ratios of either FDG or FET, however, allow distinction between low- and high-grade gliomas (P > .11). CONCLUSIONS: For brain tumor diagnosis, FET-PET performed much better than FDG and should be preferred when assessing a new isolated brain tumor. For glioma grading, however, both tracers showed similar performances.

Microcalcification evaluation in computer assisted diagnosis for digital mammography

In order to develop applications for z;isual interpretation of medical images, the early detection and evaluation of microcalcifications in digital mammograms is verg important since their presence is oftenassociated with a high incidence of breast cancers. Accurate classification into benign and malignant groups would help improve diagnostic sensitivity as well as reduce the number of unnecessa y biopsies. The challenge here is the selection of the useful features to distinguish benign from malignant micro calcifications. Our purpose in this work is to analyse a microcalcification evaluation method based on a set of shapebased features extracted from the digitised mammography. The segmentation of the microcalcificationsis performed using a fixed-tolerance region growing method to extract boundaries of calcifications with manually selected seed pixels. Taking into account that shapes and sizes of clustered microcalcificationshave been associated with a high risk of carcinoma based on digerent subjective measures, such as whether or not the calcifications are irregular, linear, vermiform, branched, rounded or ring like, our efforts were addressed to obtain a feature set related to the shape. The identification of the pammeters concerning the malignant character of the microcalcifications was performed on a set of 146 mammograms with their real diagnosis known in advance from biopsies. This allowed identifying the following shape-based parameters as the relevant ones: Number of clusters, Number of holes, Area, Feret elongation, Roughness, and Elongation. Further experiments on a set of 70 new mammogmms showed that the performance of the classification scheme is close to the mean performance of three expert radiologists, which allows to consider the proposed method for assisting the diagnosis and encourages to continue the investigation in the senseof adding new features not only related to the shape

Aportación al estudio de arcillas expansivas asociadas a las facies garumnienses de la Conca de Tremp (Prepirineo de Lleida)

Some clay levels of the garumnian facies, which surface in the southern sector of the Tremp Basin present a principal mineralogy of expansive type. The oedometer essays show that such materials present a very high grade of potencial expansivity. The swelling pressure presents values higher than 390 KN/m2. In the majority of the areas wherw this kind of clays surface the hydric erosion phenomena and the mass movements often appear to be very common and intense. The geomorphological role of the expansive clays is discussed as the triggering factor, associated to the development of these denudative processes

Paperikoneen hyötysuhteen parantaminen kunnossapidon keinoin

Stora Enson Kotkan tehtaiden paperikone yksi on pieni erikoislaatuja tekevä paperikone, jonka hy6tysuhteen parantamiseen on etsitty keinoja kunnossapidon toimesta. Kansainvälisen kilpailun kiristyessä sekä raaka aineiden ja energian kallistuessa paperikoneen hy6tysuhteen tulee olla korkealla tasolla. Tämän diplomity6n kirjallisuusosassa on perehdytty yleisesti kunnossapidon käsitteisiin ja toimintatapoihin. Vikaantumisen osiossa on pyritty l6ytamaan mekanismi laakereiden vikaantumiseen ja kunnonvalvonnalla keinot laakereiden vikaantumisen ehkäisyyn. Työn käytännön osiossa tutkittiin paperikoneen häiriökirjauksia vuosilta 2006 ja 2007 tehtaan toiminnanohjausjärjestelmistä. Samanaikaisesti selvitettiin toimenpidekirjauksia ja tehtyjä korjauksia samoihin kohteisiin, joissa vikaantumista tapahtuu. Tavoitteena oli selvittää syyt suuriin hairi6seisokkiaikoihin sekä analysoida suunniteltujen ja suunnittelemattomien seisokkien suhdetta. Tutkimuksessa havaittiin häiriökirjauksien puutteellisuus ja kirjauksien merkitys häiriöiden ennaltaehkäisyssä.

Esôfago de Barrett: aspectos fisiopatológicos e moleculares da seqüência metaplasia-displasia-adenocarcinoma - artigo de revisão

The Barrett's esophagus (BE) is defined as endoscopically visible columnar mucosa at the distal esophagus, of any extension, proved to harbor intestinal metaplasia on biopsy, highlighted by the presence of goblet cells. BE denotes long-standing gastroesophageal reflux disease (GERD) and is an important risk factor for the development of esophageal adenocarcinoma (EAC). Therefore, these patients must be on follow-up, in order to diagnose cancer early. BE patients have frequent alterations in esophageal physiologyc studies. Alkaline duodenogastroesophageal reflux seems to have important role. The development BE occurs in steps, initially with formation of cardiac type mucosa subsequent intestinalization. Futher progression can follow a sequence, from low grade dysplasia, to high grade dysplasia and esophageal adenocarcinoma. Current follow-up is based on the presence of dysplasia. It has limitations, grouping patients heterogeneously. Different steps of carcinogenesis have been studied looking for an ideal prognostic marker. Uncontrolled proliferative activity, apoptosis inhibition, angiogenesis, tissue invasion and metastases formation are all implicated in cancer origin. Some cycle cell molecules have been studied in BE, such as retinoblastoma protein, ciclins, kinase dependent ciclins and cell cycle inhibitors. The P53 protein is one of the most investigated in the metaplasia-adenocarcinoma progression. Growth Factors, apoptotic proteins, telomers and DNA ploidy have also been searched. Increased proliferative activity has been implicated in Barrett's carcinogenesis and the Ki-67 antigen, through imunohistochemical analysis, has become the the method of choice. Present in the nucleus, it is found in proliferative cells only. Some studies suport association between Ki-67 activity and the metaplasia-dysplasia-adenocarcinoma sequence.The results, however, are inconclusive and research should follow this way.

Tratamento conservador de trauma renal grave após litotripsia extracorpórea por ondas de choque

Subcapsular and perinephric hematomas are relatively common after shock-wave lithotripsy, but high-grade kidney injuries are extremely rare. We present the first case of a high-grade kidney injury after shock-wave lithotripsy managed conservatively. A 57-year-old white female patient with left 1.5cm superior ureteral calculi was submitted to shock-wave lithotripsy.

Epidemiological profile and postoperative complications of women undergoing gynecological surgery in a reference center in the northern brazilian legal amazon

Objective: To evaluate the epidemiological profile and the operative complications of patients undergoing gynecological operations for benign diseases in a tertiary public hospital in the state of Roraima, Brazil. Methods: We conducted a retrospective survey through the analysis of 518 records of patients submitted to gynecological operations between January and June 2012. We included the three major operations during this period (n = 175): hysterectomy, colpoperineoplasty and suburethral sling placement. We excluded 236 cases of tubal ligation and 25 cases where it was not possible to access to medical records. Results: The mean age was 47.6 years; the education level of most patients was completed junior high (36.6%); 77% were from the State capital, 47.4% were in stable relationships and 26.3% were housewives. The majority of patients had given birth three or more times (86.6%), with previous vaginal delivery in 50.2%, and cesarean delivery, 21%. The main diagnostic indications for surgical treatment were uterine myoma (46.3%), urinary incontinence (27.4%) and genital dystopias (17.7%). We found three cases (1.7%) of high-grade intraepithelial lesions on Pap smear. The most common procedure was total hysterectomy (19.8%), 15.5% vaginally. The most common complication was wound infection (2.2%). Conclusion: Women undergoing gynecological operations due to benign disease had a mean age of 47 years, most had levels of basic education, came from the capital, were in stable relationships, predominantly housewives, multiparous and showed low operative complication rates.

The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment

Objective: Io evaluate the expression of p16INK4a and p53 biomarkers in conization specimens from patients with high grade cervical intraepithelial neoplasia (HG-CIN), correlating them with the ability to predict the recurrence. Methods : we conducted a retrospective study of patients with HG-CIN in cervical biopsy treated with conization between January 1999 and January 2006 who had a minimum follow-up of 18 months. The expression of the p16 and p53 was assessed by tissue microarrays and correlated with disease recurrence. For analysis, we used the test of proportions (chi-square), considering value p<0.05, 95% CI and calculations of sensitivity, specificity and accuracy of these immunomarkers in predicting recurrence. Results : the series comprised 83 patients aged between 16 and 86 years (35±11.7), divided into two groups: 30 with HG-CIN recurrence (study group) and 53 without recurrence (control group). Mean age, parity, smoking and conization technique were similar in both groups. The p53 expression was present in 43% of the study group and 57% of the control group, and the p16 was present in 43% of the study group and in 57% of the control group (p>0.05). p53 had a positive predictive value (PPV) of 42% and negative predictive value (NPV) of 73%, sensitivity 70%, specificity of 47% and accuracy of 59%. The p16, PPV 42%, NPV 72%, sensitivity 66%, specificity of 49% and accuracy of 56%. Conclusion : immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment.

Internal quality control indicators of cervical cytopathology exams performed in laboratories monitored by the External Quality Control Laboratory

PURPOSE: To evaluate the impact of continued education provided by an external quality control laboratory on the indicators of internal quality control of cytopathology exams.METHODS: The internal quality assurance indicators for cytopathology exams from 12 laboratories monitored by the External Quality Control Laboratory were evaluated. Overall, 185,194 exams were included, 98,133 of which referred to the period preceding implementation of a continued education program, while 87,061 referred to the period following this intervention. Data were obtained from the Cervical Cancer Database of the Brazilian National Health Service.RESULTS: Following implementation of the continued education program, the positivity index (PI) remained within recommended limits in four laboratories. In another four laboratories, the PI progressed from below the limits to within the recommended standards. In one laboratory, the PI remained low, in two laboratories, it remained very low, and in one, it increased from very low to low. The percentage of exams compatible with a high-grade squamous intraepithelial lesion (HSIL) remained within the recommended limits in five laboratories, while in three laboratories it progressed from below the recommended levels to >0.4% of the total number of satisfactory exams, and in four laboratories it remained below the standard limit. Both the percentage of atypical squamous cells of undetermined significance (ASC-US) in relation to abnormal exams, and the ratio between ASC-US and intraepithelial lesions remained within recommended levels in all the laboratories investigated.CONCLUSION: An improvement was found in the indicators represented by the positivity index and the percentage of exams compatible with a high-grade squamous intraepithelial lesion, showing that the role played by the external quality control laboratory in providing continued education contributed towards improving laboratory staff skills in detecting cervical cancer precursor lesions.

Quality Indicators of Cervical Cytopathology Tests in the Public Service in Minas Gerais, Brazil

Objective The objective of this study is to assess the performance of cytopathology laboratories providing services to the Brazilian Unified Health System (Sistema Único de Saúde - SUS) in the State of Minas Gerais, Brazil. Methods This descriptive study uses data obtained from the Cervical Cancer Information System from January to December 2012. Three quality indicators were analyzed to assess the quality of cervical cytopathology tests: positivity index, percentage of atypical squamous cells (ASCs) in abnormal tests, and percentage of tests compatiblewith high-grade squamous intraepithelial lesions (HSILs). Laboratories were classified according to their production scale in tests per year≤5,000; from 5,001 to 10,000; from 10,001 to 15,000; and 15,001. Based on the collection of variables and the classification of laboratories according to production scale, we created and analyzed a database using Microsoft Office Excel 97-2003. Results In the Brazilian state of Minas Gerais, 146 laboratories provided services to the SUS in 2012 by performing a total of 1,277,018 cervical cytopathology tests. Half of these laboratories had production scales≤5,000 tests/year and accounted for 13.1% of all tests performed in the entire state; in turn, 13.7% of these laboratories presented production scales of > 15,001 tests/year and accounted for 49.2% of the total of tests performed in the entire state. The positivity indexes of most laboratories providing services to the SUS in 2012, regardless of production scale, were below or well below recommended limits. Of the 20 laboratories that performed more than 15,001 tests per year, only three presented percentages of tests compatible with HSILs above the lower limit recommended by the Brazilian Ministry of Health. Conclusion The majority of laboratories providing services to the SUS in Minas Gerais presented quality indicators outside the range recommended by the Brazilian Ministry of Health.

Identification of Epigenetic Targets in Prostate Cancer for Therapeutic Development

Recurrent castration resistant prostate cancer remains a challenge for cancer therapies and novel treatment options in addition to current anti-androgen and mitosis inhibitors are needed. Aberrations in epigenetic enzymes and chromatin binding proteins have been linked to prostate cancer and they may form a novel class of drug targets in the future. In this thesis we systematically evaluated the epigenenome as a prostate cancer drug target. We functionally silenced 615 known and putative epigenetically active protein coding genes in prostate cancer cell lines using high throughput RNAi screening and evaluated the effects on cell proliferation, androgen receptor (AR) expression and histone patterns. Histone deacetylases (HDACs) were found to regulate AR expression. Furthermore, HDAC inhibitors reduced AR signaling and inhibited synergistically with androgen deprivation prostate cancer cell proliferation. In particular, TMPRSS2- EGR fusion gene positive prostate cancer cell lines were sensitive to combined HDAC and AR inhibition, which may partly be related to the dependency of a fusion gene induced epigenetic pathway. Histone demethylases (HDMs) were identified to regulate prostate cancer cell line proliferation. We discovered a novel histone JmjC-domain histone demethylase PHF8 to be highly expressed in high grade prostate cancers and mediate cell proliferation, migration and invasion in in vitro models. Additionally, we explored novel HDM inhibitor chemical structures using virtual screening methods. The structures best fitting to the active pocket of KDM4A were tested for enzyme inhibition and prostate cancer cell proliferation activity in vitro. In conclusion, our results show that prostate cancer may efficiently be targeted with combined AR and HDAC inhibition which is also currently being tested in clinical trials. HDMs were identified as another feasible novel drug target class. Future studies in representative animal models and development of specific inhibitors may reveal HDMs full potential in prostate cancer therapy

Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Selective leaching of multimetal tailings

Depletion of high grade mineral resources, tightening of environmental regulations and the environmental impact of acid mine drainage caused by sulfidic minerals continuously increase the interest in processing tailings and other mine waste. Treating waste requires additional capital and operational input, but the decrease in size and need of tailings ponds and permits decrease the overall costs. Treatment and utilization of the tailings could also bring added revenue by the recovery of valuables. Leaching of metal sulfides is very demanding and time consuming and hence process conditions need to be carefully optimized. The leaching of sulfides is affected by for example the choice of leaching agent, its concentration and temperature, pH, the redox potential, pressure, pulp density and particle size distribution. With reference to the mine case study the leaching of nickel and copper sulfides, especially the primary minerals pentlandite and chalcopyrite were investigated. Leaching behavior and recoveries for nickel, copper and iron were found out by sulfuric and citric acid leaching experiments using tailings samples of high and low sulfur content. Moderate recoveries were obtained and citric acid seemed more attractive. Increase in temperature and decrease in pulp density had positive effect on the recovery and pH was also proven to have a significant effect on the recovery of valuables. The rate determining step was determined through kinetic modeling in case of all valuables separately. Leaching was controlled by diffusion. The investigated multimetal tailing showed moderate potential in recovering of metal valuables from low grade tailing deposits. The process conditions should however be further optimized.

EGFR, Her2, p53 ja ALDH1:n yhteys munasarjasyöpäpotilaiden ennusteeseen, ja tilastoja TYKSin vuosien 2001–2007 munasarjasyöpään sairastuneiden potilaiden aineistosta

Munasarjasyöpä on Suomessa tappavin ja toiseksi yleisin gynekologinen syöpä, lisäksi se on kymmenenneksi yleisin naisten syöpä. Yli 90% munasarjasyövistä on epiteeliperäisiä ja morfologisista alatyypeistä yleisin on seroosi syöpä. Serooseista syövistä yli 90 % on korkean riskin eli high grade –syöpää. Vaikka uudet hoidot ovat pidentäneet potilaan selviytymistä, niin kaiken kaikkiaan kokonaisennuste ei kuitenkaan ole parantunut viimeisen vuosikymmenen aikana. Aikaisin havaittu paikallinen epiteeliperäinen munasarjasyöpä on parannettavissa kirurgialla. Yli 2/3 epiteliaalisista munasarjasyövistä diagnosoidaan vasta levinneessä vaiheessa, jolloin viiden vuoden selviytyvyys potilailla on vain noin 30 %. Aiemmin munasarjasyöpien arveltiin olevan lähtöisin munasarjojen pintaepiteelistä, mutta uusimpien tutkimusten mukaan kyseessä on niin molekulaarisesti kuin etiologisesti ryhmä eri syöpiä, jotka ilmenevät samassa anatomisessa paikassa. Syventävässä työssäni tutkin munasarjasyövän käyttäytymistä ennustavia merkkiaineita Merkkiaineita tutkimalla pyritään tulevaisuudessa ennustamaan paremmin syöpien käyttäytymistä ja antamaan potilaille parempia täsmähoitoja. Syventävien opintojeni tarkoituksena oli tutkia munasarjasyöpää kirjallisuuteen tutustumalla ja tutkimalla retrospektiivistä vuosien 2001–2007 munasarjapotilasaineistoa. Keräsimme toisen tutkijan kanssa aineistoon 356 potilaan tiedot, joista 310 sisällytettiin tekemiini tilastoihin. Lisäksi tutkin kiinnostavia munasarjasyövän käyttäytymiseen mahdollisesti liittyviä merkkiaineita (EGFR, HER2, P53 JA ALDH1) uudessa 48 potilaan aineistossa ja selvitin proteiinien merkitystä taudin kulussa ja ennusteessa. 310 potilaan aineiston tulokset olivat sopusoinnussa aiempiin julkaisuihin. Aineistomme munasarjasyövistä 60 % on seroosia high grade –syöpää ja 67 % syövistä on levinneen vaiheen eli luokan III-IV tauteja. 48 potilaan immunohistokemiallisissa värjäyksissä mielenkiintoisin tulos on se, että Her2 :n värjäytymisintensiteetti korreloi kääntäen vahvaan ALDH1-värjäykseen eli se on korkea, kun ALDH1 on matala (korrelaatio -0.425; p=0.00994) Vastaavasti Her2 :n intensiteetin ollessa korkea ALDH1/heikko-soluja on paljon (p=0.00975). Tällaista tutkimus tulosta ei aiemmin ole esitetty. Tämä kiinnostava tulos tulee jatkossa varmistaa laajemmassa aineistossa.