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2.
BJS Open ; 4(2): 310-319, 2020 04.
Article in English | MEDLINE | ID: mdl-32207577

ABSTRACT

BACKGROUND: The impact of hospital volume after rectal cancer surgery is seldom investigated. This study aimed to analyse the impact of annual rectal cancer surgery cases per hospital on postoperative mortality and failure to rescue. METHODS: All patients diagnosed with rectal cancer and who had a rectal resection procedure code from 2012 to 2015 were identified from nationwide administrative hospital data. Hospitals were grouped into five quintiles according to caseload. The absolute number of patients, postoperative deaths and failure to rescue (defined as in-hospital mortality after a documented postoperative complication) for severe postoperative complications were determined. RESULTS: Some 64 349 patients were identified. The overall in-house mortality rate was 3·9 per cent. The crude in-hospital mortality rate ranged from 5·3 per cent in very low-volume hospitals to 2·6 per cent in very high-volume centres, with a distinct trend between volume categories (P < 0·001). In multivariable logistic regression analysis using hospital volume as random effect, very high-volume hospitals (53 interventions/year) had a risk-adjusted odds ratio of 0·58 (95 per cent c.i. 0·47 to 0·73), compared with the baseline in-house mortality rate in very low-volume hospitals (6 interventions per year) (P < 0·001). The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue decreased significantly with increasing caseload (15·6 per cent after pulmonary embolism in the highest volume quintile versus 38 per cent in the lowest quintile; P = 0·010). CONCLUSION: Patients who had rectal cancer surgery in high-volume hospitals showed better outcomes and reduced failure to rescue rates for severe complications than those treated in low-volume hospitals.


ANTECEDENTES: El impacto del volumen hospitalario en los resultados de la cirugía del cáncer de recto ha sido poco investigado. Este estudio tuvo como objetivo analizar el impacto de los casos anuales de cirugía de cáncer de recto por hospital en la mortalidad postoperatoria (postoperative mortality, POM) y el fracaso en el rescate (failure to rescue, FtR). MÉTODOS: Todos los casos de pacientes hospitalizados con un diagnóstico de cáncer de recto y un código de procedimiento de resección rectal, tratados de 2012 a 2015, se identificaron a partir de datos hospitalarios administrativos a nivel nacional. Los hospitales se agruparon en cinco quintiles según el volumen de casos. Se determinó el número absoluto de pacientes, la POM y el FtR por complicaciones postoperatorias graves. El FtR se definió como la mortalidad hospitalaria después de una complicación postoperatoria documentada. RESULTADOS: Se identificaron 64.349 casos entre 2012 y 2015. La tasa de mortalidad hospitalaria global fue del 3,89% (n = 2.506). Las tasas brutas de mortalidad hospitalaria variaron de 5,34% (n = 687) en hospitales de muy bajo volumen a 2,63% (n = 337) en centros de muy alto volumen, con una tendencia distinta entre las categorías de centros (P < 0,001). En el análisis de regresión logística multivariante utilizando el volumen hospitalario como efecto aleatorio, los hospitales de muy alto volumen (53 intervenciones/año) tenían una razón de oportunidades (odds ratio, OR) ajustada por riesgo de 0,58 (i.c. del 95%: 0,47-0,73) en comparación con la tasa basal de mortalidad hospitalaria en hospitales de muy bajo volumen (6 intervenciones/año) (P < 0,001). La tasa global de complicaciones postoperatorias fue comparable entre los diferentes quintiles de volumen, pero el FtR disminuyó significativamente con el aumento del volumen de casos (15,63% FtR tras una embolia pulmonar en el quintil más alto versus 38,4% en el hospital del quintil más bajo, P = 0,01). CONCLUSIÓN: Los pacientes sometidos a cirugía de cáncer de recto en hospitales de gran volumen presentaron mejores resultados y una disminución de las tasas de fracaso en el rescate por complicaciones graves en comparación con los pacientes tratados en hospitales de bajo volumen.


Subject(s)
Hospital Mortality/trends , Rectal Neoplasms/mortality , Rectal Neoplasms/surgery , Aged , Aged, 80 and over , Comorbidity , Female , Germany/epidemiology , Hospitals, High-Volume/statistics & numerical data , Hospitals, Low-Volume/statistics & numerical data , Humans , Logistic Models , Male , Middle Aged , Outcome Assessment, Health Care , Rectal Neoplasms/epidemiology , Rectal Neoplasms/pathology , Registries , Retrospective Studies
3.
Chirurg ; 91(5): 405-412, 2020 May.
Article in German | MEDLINE | ID: mdl-31915871

ABSTRACT

During the last two decades a neoadjuvant treatment concept has been established for an increasing number of malignant tumors of the gastrointestinal tract; however, these concepts are still subject to a constant change concerning the indications and type of treatment. A prime example for this is rectal cancer. The rate of local recurrence in particular was significantly reduced by neoadjuvant therapy but until now it has not been possible to validly show an improvement in overall or disease-free survival. At the beginning of the millennium it was recommended to treat every rectal carcinoma in UICC stages II and III with neoadjuvant therapy, independent of the height localization. In the meantime this has increasingly been relativized and only locally advanced tumors of the middle and lower thirds of the rectum should be pretreated, whereas tumors of the upper third of the rectum should basically be treated in the same way as colon cancer. It is to be expected that there will be further differentiation concerning the indications in this context in the future mainly based on a preoperative magnetic resonance imaging (MRI) examination. At the same time, initial studies for colon cancer show that neoadjuvant chemotherapy can be beneficial and that an optimized computed tomography (CT) scan can be a worthwhile tool with respect to pretherapeutic stratification of patients.


Subject(s)
Colonic Neoplasms , Rectal Neoplasms , Chemoradiotherapy , Humans , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Neoplasm Staging , Patient Selection , Treatment Outcome
4.
Neoplasia ; 21(11): 1110-1120, 2019 11.
Article in English | MEDLINE | ID: mdl-31734632

ABSTRACT

The transcriptional regulator BRD4 has been shown to be important for the expression of several oncogenes including MYC. Inhibiting of BRD4 has broad antiproliferative activity in different cancer cell types. The small molecule JQ1 blocks the interaction of BRD4 with acetylated histones leading to transcriptional modulation. Depleting BRD4 via engineered bifunctional small molecules named PROTACs (proteolysis targeting chimeras) represents the next-generation approach to JQ1-mediated BRD4 inhibition. PROTACs trigger BRD4 for proteasomale degradation by recruiting E3 ligases. The aim of this study was therefore to validate the importance of BRD4 as a relevant target in colorectal cancer (CRC) cells and to compare the efficacy of BRD4 inhibition with BRD4 degradation on downregulating MYC expression. JQ1 induced a downregulation of both MYC mRNA and MYC protein associated with an antiproliferative phenotype in CRC cells. dBET1 and MZ1 induced degradation of BRD4 followed by a reduction in MYC expression and CRC cell proliferation. In SW480 cells, where dBET1 failed, we found significantly lower levels of the E3 ligase cereblon, which is essential for dBET1-induced BRD4 degradation. To gain mechanistic insight into the unresponsiveness to dBET1, we generated dBET1-resistant LS174t cells and found a strong downregulation of cereblon protein. These findings suggest that inhibition of BRD4 by JQ1 and degradation of BRD4 by dBET1 and MZ1 are powerful tools for reducing MYC expression and CRC cell proliferation. In addition, downregulation of cereblon may be an important mechanism for developing dBET1 resistance, which can be evaded by incubating dBET1-resistant cells with JQ1 or MZ1.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Cycle Proteins/antagonists & inhibitors , Gene Expression Regulation, Neoplastic/drug effects , Proto-Oncogene Proteins c-myc/genetics , Transcription Factors/antagonists & inhibitors , Azepines/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Humans , Models, Biological , Protein Binding , Proteolysis , Transcription, Genetic/drug effects , Triazoles/pharmacology , Ubiquitin-Protein Ligases/metabolism
5.
BJS Open ; 3(5): 672-677, 2019 10.
Article in English | MEDLINE | ID: mdl-31592096

ABSTRACT

Background: Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods: Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identified from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results: Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5·8 per cent, ranging from 6·9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4·8 per cent (1239 of 25 825) in very high-volume centres (P < 0·001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0·75 (95 per cent c.i. 0·66 to 0·84) in very high-volume hospitals performing a mean of 85·0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12·7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion: In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals.


Subject(s)
Colonic Neoplasms/mortality , Colonic Neoplasms/surgery , Hospital Mortality/trends , Aged , Aged, 80 and over , Colonic Neoplasms/epidemiology , Colonic Neoplasms/pathology , Comorbidity , Female , Gastrointestinal Neoplasms/pathology , Germany/epidemiology , Hospitals, High-Volume/statistics & numerical data , Hospitals, Low-Volume/statistics & numerical data , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Registries
6.
Clin Radiol ; 74(11): 894.e1-894.e9, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31288924

ABSTRACT

AIM: To evaluate the effect of pre-biopsy magnetic resonance imaging (MRI) on cancer diagnostic times, and to report MRI-directed pathology outcomes. MATERIALS AND METHODS: In total, 1483 patients were referred with prostate cancer suspicion during a 30-month period. Upfront MRI was performed in 745 patients: 332 MRIs in the 15 months prior to dedicated scanning slots (group 1), and 413 in the 15 months post-introduction (group 2). A further 88 patients had initial MRI following clinical assessment. Biopsy via the transrectal (TR) or transperineal (TP) approach was performed, with MRI/ultrasound fusion for MRI targets. Clinically significant cancer (csPCa) was defined as Gleason ≥3+4. Negative MRIs were defined as Likert 1-2. Per-case clinical decisions were taken to biopsy or not. RESULTS: 44.4% of patients avoided biopsy. 484/833 (58.1%) MRIs were negative; 37.4% of these patients had biopsy with a negative predictive value (NPV) of 92.8% for Gleason ≥3+4 and 98.3% for ≥4+3. Overall prostate cancer prevalence was 34.3% (24.6% csPCa). In 323 MRI-positive cases, any cancer was present in 78.9% (csPCa 60.4%). Of the 1483 patients, 1232 (83.1%) completed all diagnostic tests within 28 days. Upfront MRI patients met this standard in 621/833 (74.5%), improving from 66.9% to 81.1% with reserved slots (group 2) with a reduced diagnostic time from median 25.5 to 20.9 days. Biopsy scheduling delayed the pathway in 69.7%, with MRI responsible in 22.3%, reducing to 10.3% in group 2. TP biopsies met the 28-day standard in significantly less cases (29.7%), compared to TR (67.4%, p<0.0001). CONCLUSION: Reserved MRI slots reduces time-to-diagnosis, and upfront MRI safely avoids biopsy in a significant proportion of men, whilst maintaining expected csPCa detection rates.


Subject(s)
Multiparametric Magnetic Resonance Imaging/methods , Prostate/pathology , Prostatic Neoplasms/pathology , Aged , Critical Pathways , Early Detection of Cancer , Humans , Image-Guided Biopsy/methods , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Retrospective Studies , Time Factors , Treatment Outcome
7.
BJS Open ; 3(2): 203-209, 2019 04.
Article in English | MEDLINE | ID: mdl-30957068

ABSTRACT

Background: Despite recent improvements in colonic cancer surgery, the rate of anastomotic leakage after right hemicolectomy is still around 6-7 per cent. This study examined whether anastomotic technique (handsewn or stapled) after open right hemicolectomy for right-sided colonic cancer influences postoperative complications. Methods: Patient data from the German Society for General and Visceral Surgery (StuDoQ) registry from 2010 to 2017 were analysed. Univariable and multivariable analyses were performed. The primary endpoint was anastomotic leakage; secondary endpoints were postoperative ileus, complications and length of postoperative hospital stay (LOS). Results: A total of 4062 patients who had undergone open right hemicolectomy for colonic cancer were analysed. All patients had an ileocolic anastomosis, 2742 handsewn and 1320 stapled. Baseline characteristics were similar. No significant differences were identified in anastomotic leakage, postoperative ileus, reoperation rate, surgical-site infection, LOS or death. The stapled group had a significantly shorter duration of surgery and fewer Clavien-Dindo grade I-II complications. In multivariable logistic regression analysis, ASA grade and BMI were found to be significantly associated with postoperative complications such as anastomotic leakage, postoperative ileus and reoperation rate. Conclusion: Handsewn and stapled ileocolic anastomoses for open right-sided colonic cancer resections are equally safe. Stapler use was associated with reduced duration of surgery and significantly fewer minor complications.


Subject(s)
Anastomotic Leak/epidemiology , Colectomy/adverse effects , Colonic Neoplasms/surgery , Ileus/epidemiology , Suture Techniques/adverse effects , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/instrumentation , Anastomosis, Surgical/methods , Anastomotic Leak/etiology , Colectomy/instrumentation , Colectomy/methods , Colon/pathology , Colon/surgery , Colonic Neoplasms/pathology , Female , Humans , Ileus/etiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Readmission/statistics & numerical data , Prospective Studies , Registries/statistics & numerical data , Reoperation/statistics & numerical data , Surgical Staplers/adverse effects , Suture Techniques/instrumentation , Treatment Outcome
8.
Chirurg ; 90(3): 194-201, 2019 Mar.
Article in German | MEDLINE | ID: mdl-30456645

ABSTRACT

Tumors of the appendix are not a uniform group but differ significantly in terms of their origin/histology and metastatic behavior. Furthermore, tumors of the appendix are often diagnosed as incidental findings after appendectomy for acute appendicitis. A subgroup of these neoplasms are low-grade appendiceal mucinous neoplasms (LAMN). These are mucus-forming tumors of the appendiceal lumen, which can lead to rupture of the appendix and seeding into the abdominal cavity. Therefore LAMN are considered precursors of pseudomyxoma peritonei (PMP). It is essential to clearly differentiate the subgroups of LAMN as well as the resection status. According to this it is determined whether (radical) appendectomy is a sufficient therapy or further treatment, such as ileocecal resection with hyperthermic intraperitoneal chemotherapy (HIPEC) or cytoreductive surgery (CRS) is necessary. There is no standardized concept regarding the follow-up after resection of LAMN. Generally, it is recommended to perform a computed tomography (CT) scan of the abdomen and determination of tumor markers 6 months postoperatively and then once a year. A recommendation regarding the duration of follow-up is difficult as there are case reports in which PMP has occurred more than 15 years after removal of LAMN.


Subject(s)
Adenocarcinoma, Mucinous , Appendiceal Neoplasms , Appendicitis , Incidental Findings , Peritoneal Neoplasms , Pseudomyxoma Peritonei , Adenocarcinoma, Mucinous/diagnosis , Appendiceal Neoplasms/diagnosis , Appendicitis/complications , Humans
9.
RSC Adv ; 8(26): 14377-14388, 2018 Apr 17.
Article in English | MEDLINE | ID: mdl-35540747

ABSTRACT

The application of appropriate analytical techniques is essential for nanomaterial (NM) characterization. In this study, we compared different analytical techniques for NM analysis. Regarding possible adverse health effects, ionic and particulate NM effects have to be taken into account. As NMs behave quite differently in physiological media, special attention was paid to techniques which are able to determine the biosolubility and complexation behavior of NMs. Representative NMs of similar size were selected: aluminum (Al0) and aluminum oxide (Al2O3), to compare the behavior of metal and metal oxides. In addition, titanium dioxide (TiO2) was investigated. Characterization techniques such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were evaluated with respect to their suitability for fast characterization of nanoparticle dispersions regarding a particle's hydrodynamic diameter and size distribution. By application of inductively coupled plasma mass spectrometry in the single particle mode (SP-ICP-MS), individual nanoparticles were quantified and characterized regarding their size. SP-ICP-MS measurements were correlated with the information gained using other characterization techniques, i.e. transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). The particle surface as an important descriptor of NMs was analyzed by X-ray diffraction (XRD). NM impurities and their co-localization with biomolecules were determined by ion beam microscopy (IBM) and confocal Raman microscopy (CRM). We conclude advantages and disadvantages of the different techniques applied and suggest options for their complementation. Thus, this paper may serve as a practical guide to particle characterization techniques.

10.
Eur J Radiol ; 95: 307-313, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28987685

ABSTRACT

PURPOSE: To evaluate sub-differentiation of PI-RADS-3 prostate lesions using pre-defined T2- and diffusion-weighted (DWI) MRI criteria, to aid the biopsy decision process. METHODS: 143 patients with PIRADS-3 index lesions on MRI underwent targeted transperineal-MR/US fusion biopsy. Radiologists with 2 and 7-years experience performed blinded retrospective second-reads using set criteria and assigned biopsy recommendations. Inter-reader agreement, Gleason score (GS), positive (PPV) predictive values (±95% confidence intervals) were calculated and compared by Fisher's exact test with Bonferroni-Hom correction. RESULTS: 43% (61/143) patients had GS 6-10 and 21% (30/143) GS≥3+4 cancer. For peripheral zone lesions, significant differences in any cancer detection were found for shape (0.26±0.13 geographical vs. 0.69±0.23 rounded; p=0.0055) and ADC (mild 0.21±0.12 vs marked 0.81±0.19; p=0.0001). For transition zone, significantly increased cancer detection was shown for location (anterior 0.63±0.15 vs. mid/posterior 0.31±0.14; p=0.0048), border (pseudo-capsule 0.32±0.14 vs. ill-defined 0.61±0.15; p=0.0092), and ADC (mild 0.35±0.12 vs marked restriction 0.68±0.17; p=0.0057). Biopsy recommendations had 62% inter-reader agreement (89/143). Experienced reader PPVs were significantly higher for any cancer with "biopsy-recommended" 0.61±0.11 vs. "no biopsy" 0.21±0.10 (p=0.0001), and for GS 7-10 cancers: 0.32±0.10 vs. 0.08±0.07, respectively (p=0.0003). CONCLUSION: Identification of certain objective imaging criteria as well as a subjective biopsy recommendation from an experienced radiologist can help to increase the predictive value of equivocal prostate lesions and inform the decision making process of whether or not to biopsy.


Subject(s)
Magnetic Resonance Imaging/methods , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Radiology Information Systems/statistics & numerical data , Aged , Clinical Decision-Making , Diagnosis, Differential , Humans , Male , Middle Aged , Prostatic Neoplasms/pathology , Reproducibility of Results , Retrospective Studies
11.
World J Urol ; 35(5): 695-701, 2017 May.
Article in English | MEDLINE | ID: mdl-27637908

ABSTRACT

PURPOSE: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). METHODS: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. RESULTS: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. CONCLUSIONS: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.


Subject(s)
Magnetic Resonance Imaging , Prostatic Neoplasms/diagnostic imaging , Ablation Techniques , Biopsy , Cryosurgery , Delphi Technique , Electrochemotherapy , High-Intensity Focused Ultrasound Ablation , Humans , Laser Therapy , Male , Pathologists , Photochemotherapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Radiologists , Surveys and Questionnaires , Urologists
12.
Sci Rep ; 6: 35364, 2016 10 17.
Article in English | MEDLINE | ID: mdl-27748407

ABSTRACT

Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy in men with suspected prostate cancer. Here we investigated the value of combining both tests in men requiring a repeat biopsy. PHI scores were measured in men undergoing re-biopsy with an mpMRI image-guided transperineal approach (n = 279, 94 with negative mpMRIs). The PHI was assessed for ability to add value to mpMRI in predicting all or only significant cancers (Gleason ≥7). In this study adding PHI to mpMRI improved overall and significant cancer prediction (AUC 0.71 and 0.75) compared to mpMRI + PSA alone (AUC 0.64 and 0.69 respectively). At a threshold of ≥35, PHI + mpMRI demonstrated a NPV of 0.97 for excluding significant tumours. In mpMRI negative men, the PHI again improved prediction of significant cancers; AUC 0.76 vs 0.63 (mpMRI + PSA). Using a PHI≥35, only 1/21 significant cancers was missed and 31/73 (42%) men potentially spared a re-biopsy (NPV of 0.97, sensitivity 0.95). Decision curve analysis demonstrated clinically relevant utility of the PHI across threshold probabilities of 5-30%. In summary, the PHI adds predictive performance to image-guided detection of clinically significant cancers and has particular value in determining re-biopsy need in men with a negative mpMRI.


Subject(s)
Magnetic Resonance Imaging , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/physiopathology , Aged , Aged, 80 and over , Area Under Curve , Biomarkers, Tumor/metabolism , Biopsy , Humans , Male , Middle Aged , Predictive Value of Tests , Probability , Prospective Studies , Prostate/pathology , Reproducibility of Results
13.
World J Urol ; 34(10): 1373-82, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26892160

ABSTRACT

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.


Subject(s)
Consensus , Delphi Technique , Prostatic Neoplasms/therapy , Quality of Life , Combined Modality Therapy/standards , Humans , Male , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Surveys and Questionnaires
16.
Fungal Genet Biol ; 47(12): 962-72, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20816830

ABSTRACT

Light is a major environmental stimulus that has a broad effect on organisms, triggering a cellular response that results in an optimal adaptation enhancing fitness and survival. In fungi, light affects growth, and causes diverse morphological changes such as those leading to reproduction. Light can also affect fungal metabolism, including the biosynthesis of natural products. In this study we show that in Aspergillus nidulans the effect of light on the production of the sterigmatocystin (ST) toxin depends on the glucose concentration. In cultures grown with 1% glucose and exposed to light, ST production was lower than when grown in the dark. This lower ST production coincided with an elevated rate of cellular damage with partial loss of nuclear integrity and vacuolated cytoplasm. However, in cultures grown with 2% glucose these effects were reversed and light enhanced ST production. Glucose abundance also affected the light-dependent subcellular localization of the VeA (velvet) protein, a key regulator necessary for normal light-dependent morphogenesis and secondary metabolism in Aspergilli and other fungal genera. The role of other VeA-associated proteins, particularly the blue-light-sensing proteins LreA and LreB (WC-1 and WC-2 orthologs), on conidiation could also be modified by the abundance of glucose. We also show that LreA and LreB, as well as the phytochrome FphA, modulate not only the synthesis of sterigmatocystin, but also the production of the antibiotic penicillin.


Subject(s)
Aspergillus nidulans/growth & development , Aspergillus nidulans/radiation effects , Glucose/metabolism , Morphogenesis , Sterigmatocystin/biosynthesis , Aspergillus nidulans/genetics , Aspergillus nidulans/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal/radiation effects , Light , Morphogenesis/radiation effects , Penicillins/metabolism , Protein Transport/radiation effects
17.
J Food Sci ; 75(2): T35-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20492264

ABSTRACT

Regulations and publications about food contaminated during ammonia refrigerant leaks provide limited information and recommendations, which means that contaminated products are often held for an indeterminate period or condemned. Moreover, the scientific literature offers little guidance on disposing of products exposed to low levels of ammonia refrigerant gas. We evaluated meat contaminated with low levels of ammonia under frozen storage conditions. Fresh beef semitendinosus muscles were trimmed of external fat; fabricated into 10 x 5 x 2.3 cm (height x width x depth) steaks; and exposed to 50, 100, 250, and 500 ppm ammonia gas (85 mL/min) in a plexiglass enclosure contained in a freezer for 6, 12, 24, and 48 h at -17 +/- 3 degrees C. Ammonia content in meat was analyzed by the indophenol method, and pH was measured according to AOAC official method 981.12. Ammonia levels and pH values increased significantly (P < 0.05) in the exposed meat with increasing exposure times and ammonia concentrations. Ammonia levels were 34.2, 51.5, 81.1, and 116 ppm, and pH values ranged from 5.56 to 5.75 (control range 5.31 to 5.43) when the meat was exposed to 50, 100, 250, 500 ppm for 48 h. Our results showed that meat ammonia content was low even with ammonia exposures as high as 500 ppm at freezing temperatures.


Subject(s)
Ammonia/analysis , Food Contamination , Food Handling/methods , Food Preservation/methods , Freezing , Meat/analysis , Animals , Cattle , Hydrogen-Ion Concentration , Indophenol/analysis , Time Factors
18.
Endoscopy ; 42(1): 28-33, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20066590

ABSTRACT

BACKGROUND AND STUDY AIMS: To compare the rate of detection of colorectal neoplastic lesions using the selective photosensitizer precursor hexaminolevulinate (HAL) combined with a new fluorescence video endoscope system against that of standard white light endoscopy, and secondarily, to evaluate the safety profile of HAL-induced fluorescence colonoscopy. PATIENTS AND METHODS: This prospective phase II clinical pilot study from two hospital study centers included 25 patients with known or highly suspected colorectal neoplasia. They underwent sensitization with locally applied 500 ml HAL enemas at a concentration of 1.6 mmol/L. At 60 minutes after enteral HAL administration, fluorescence imaging was done using a special light source capable of delivering either white light or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. RESULTS: Using histology as the gold standard, 55 / 93 of neoplastic lesions were detected with white light endoscopy, 53 / 93 with both white and blue light, 38 / 93 with blue light and second-pass white light, and 27/93 with blue light only. Of all neoplastic lesions, 91 / 93 revealed red fluorescence under fluorescence imaging ( P < 0.0001). Fluorescence mode showed 38.7 % (36 / 93) more neoplasms than did white light endoscopy. An isolated slight elevation of bilirubin, by a factor of 1.5, was noted after the administration of HAL. CONCLUSIONS: Administration of HAL as enema induces selective lesion fluorescence and increases lesion detection rate in patients with colorectal neoplasia, especially of flat, nonvisible adenomas.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Colonic Neoplasms/pathology , Colonoscopy/methods , Photosensitizing Agents , Aged , Female , Fluorescence , Humans , Male
19.
Endoscopy ; 40(2): 106-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18197583

ABSTRACT

BACKGROUND AND STUDY AIMS: We aimed to determine the feasibility of obtaining selective fluorescence of precancerous/cancerous lesions in the colon with a new fluorescence video endoscope system in combination with the selective photosensitizer precursor hexaminolevulinate (HAL), and to carry out a dose-finding study with evaluation of the optimal dose and application time. PATIENTS AND METHODS: 12 patients with colorectal lesions underwent sensitization with locally applied HAL enemas in two concentrations (0.8 mmol and 1.6 mmol). The examination was conducted either 30 or 60 minutes after rectal administration of the sensitizer, using a special light source capable of delivering either white or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. Corresponding endoscopic, fluorescence, and microscopic findings were compared. RESULTS: Using histological findings as the gold standard, 52/53 of the premalignant/malignant lesions showed red fluorescence under the photodynamic diagnosis (PDD) examination; 38/53 were detected with white-light endoscopy. The PDD mode showed 28 % more polyps than did white-light endoscopic imaging. The greatest fluorescence intensity in precancerous lesions was found with retention for 60 minutes of 500 ml of 1.6 mmol HAL. CONCLUSIONS: Administration of HAL enema induces selective lesion fluorescence and increases the lesion detection rate in patients with colorectal adenoma and early carcinoma.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Colonic Neoplasms/pathology , Colonic Polyps/diagnosis , Colonoscopy/methods , Photosensitizing Agents , Precancerous Conditions/diagnosis , Aged , Biopsy, Needle , Colonic Neoplasms/prevention & control , Colonic Polyps/pathology , Early Diagnosis , Feasibility Studies , Female , Fluorescence , Humans , Immunohistochemistry , Male , Middle Aged , Precancerous Conditions/pathology , Sensitivity and Specificity
20.
Prostate Cancer Prostatic Dis ; 9(3): 270-4, 2006.
Article in English | MEDLINE | ID: mdl-16770340

ABSTRACT

INTRODUCTION: Multidisciplinary team (MDT) meetings use precise prognostic factors to select treatment options for patients with prostate cancer. Comorbidity is judged subjectively. Recent publications favour the Charlson comorbidity score (CS) for the use in the management of prostate cancer. We assess the feasibility of using the CS by our MDT in planning the treatment of patients with prostate cancer. PATIENTS AND METHODS: Patients from the histopathology database aged less than 75 years and with a diagnosis of localized prostate cancer between 1993 and 1995 were included in a notes audit. A second group consisted of patients recommended for curative treatment for localized prostate cancer by the local MDT in 2004. Data on comorbidity, prostatic malignancy and survival up to 10 years was collected. The prognostic accuracy of the CS was assessed for those patients offered radical treatment between 1993 and 1995. RESULTS: Of 1043 patients initially assessed, 37 patients with localized prostate cancer were identified. Using Cox regression, we found the CS to be a statistically significant predictor of survival, following radical treatment for localized prostate cancer (P=0.005). Current practice in 2004 (56 patients) shows a mean (range) Charlson probability of 10-year survival for radical prostatectomy of 0.823 (0.592-0.923) and for radical radiotherapy of 0.653 (0.07-0.936). CONCLUSIONS: Our results support the findings of recent research. We also found the CS easy to calculate and therefore feasible to use in our MDT setting. We propose the introduction of the Charlson score by prostate cancer MDTs to assess age and comorbidity.


Subject(s)
Carcinoma/diagnosis , Interdisciplinary Communication , Prostatic Neoplasms/diagnosis , Research Design , Acquired Immunodeficiency Syndrome/complications , Adult , Aged , Aged, 80 and over , Carcinoma/complications , Carcinoma/mortality , Carcinoma/therapy , Cardiovascular Diseases/complications , Comorbidity , Diabetes Complications/diagnosis , Disease-Free Survival , Feasibility Studies , Humans , Kidney Diseases, Cystic/complications , Liver Diseases/complications , Lung Diseases/complications , Male , Middle Aged , Prognosis , Prostatic Neoplasms/complications , Prostatic Neoplasms/mortality , Prostatic Neoplasms/therapy , Survival Analysis
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