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1.
J Robot Surg ; 17(6): 2881-2888, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37816994

RESUMO

Roux-en-Y gastric bypass (RYGB) in patients with body mass index (BMI) ≥ 50 kg/m2 is a challenging procedure and BMI ≥ 50 kg/m2 has been identified as independent risk factor for postoperative complications and increased morbidity in previous studies. The objective of the present study was to assess whether a BMI ≥ 50 kg/m2 and various established risk factors maintain their significance in patients undergoing fully robotic RYGB (rRYGB). A single-center analysis of prospectively collected data of 113 consecutive patients undergoing standardized rRYGB with robotic stapling technique and hand-sewn gastrojejunostomy using the daVinci Xi system. Surgical outcomes were analyzed considering a number of individual perioperative risk factors including BMI ≥ 50 kg/m2. The mean BMI of the total cohort was 50.6 ± 5.5 kg/m2 and 63.7% of patients had a BMI ≥ 50 kg/m2. There were no major surgical and perioperative complications in patients with BMI ≥ 50 kg/m2 as well as in those with BMI < 50 kg/m2 after rRYGB. We identified female sex and surgeon experience but neither body weight, BMI, metabolic disorders, ASA nor EOSS scores as independent factors for shorter operation times (OT) in multivariate analyses. Complication rates and length of hospital stay (LOS) did not significantly differ between patients with potential risk factors and those without. rRYGB is a safe procedure in both, patients with BMI ≥ 50 kg/m2 and with BMI < 50 kg/m2. Higher body weight and BMI did affect neither OT nor LOS. A fully robotic approach for RYGB might help to overcome "traditional" risk factors identified in conventional laparoscopic bariatric surgery. However, larger and prospective studies are necessary to confirm these results.


Assuntos
Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Índice de Massa Corporal , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Prospectivos , Resultado do Tratamento , Estudos Retrospectivos , Redução de Peso , Fatores de Risco , Laparoscopia/métodos
2.
Clin Exp Metastasis ; 40(3): 235-242, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37093320

RESUMO

Long-term therapy for unresectable colorectal liver metastases remains challenging. Intraarterial treatments aim to avoid systemic adverse effects of chemotherapy. Nanoliposomal cytotoxic drugs manage to increase the drug concentration within the tumor while reducing toxicity in healthy tissue.  In this study we analyzed the effect of hepatic arterial infusion (HAI) with nanoliposomal irinotecan with or without the combination of embolization particles in a rat model for colorectal liver metastases. For the study 32 WAG/Rij rats received subcapsular tumor implantation with CC531 rat colonic adenocarcinoma cells. After ten days tumor size was assessed via ultrasound and animals underwent HAI. One group served as control receiving NaCl 0.9 % (Sham), the three treatment groups received either nanoliposomal irinotecan (HAI nal iri), Embocept® S (HAI Embo) or Embocept® S and nanoliposomal irinotecan (HAI Embo+nal iri). Three days after treatment animals were sacrificed after assessment of tumor size. As a result all treatment groups showed a significant reduction in tumor growth compared to Sham (p<0.05). Expression of the apoptosis marker caspase-3 was enhanced in HAI nal iri and HAI Embo+nal iri compared to Sham and HAI Embo and  even significantly enhanced after HAI Embo+nal iri in comparison to Sham (p<0.05). We were able to show that HAI with Embocept® S led to significantly reduced tumor growth while HAI with nanoliposomal irinotecan alone or in combination with Embocept® S even led to a reduction of tumor size. Thus, we demonstrate that intraarterial treatment with nanoliposomal irinotecan effectively inhibits tumor growth in a rat model of colorectal liver metastases and demands further investigation.


Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Ratos , Animais , Irinotecano , Apoptose , Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/secundário , Neoplasias do Colo/patologia , Infusões Intra-Arteriais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artéria Hepática , Fluoruracila
3.
J Robot Surg ; 17(2): 577-585, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35994194

RESUMO

The use of robotic systems in bariatric surgery has constantly increased over the last years. However, beside its technical advantages in morbidly obese patients the conclusive role of robotics in bariatric and metabolic surgery is still under controversial debate. This is an analysis of prospectively collected data of consecutive patients undergoing fully robotic Roux-en-Y gastric bypasses (TR-RYGB) during the first year after implementation of a robotic bariatric program at a tertiary university hospital. All patients were operated by a previously untrained robotic but experienced laparoscopic bariatric surgeon using the daVinci Xi system (Intuitive Surgical, Sarl). Data recording included patient characteristics, operative and functional outcomes, complications and learning curves for surgeon and assistants. In total, 80 patients underwent primary or revisional robotic bariatric surgery. Seventy-two patients (90%) received a TR-RYGB. There were no major complications, re-interventions or readmissions. The overall complication rate was 2.5% (Clavien-Dindo grade I and II). The overall operation time was 140.7 ± 24.6 min and decreased significantly from the first to the last decade of procedures (procedure 1-10: 171.2 ± 26.3 min versus procedure 63-72: 116.0 ± 10.9 min, p < 0.0001). A stabilization of the learning curve was observed after 30 procedures for the surgeon and after five procedures for the bedside assistant. With immediate effect, TR-RYGB is a safe procedure with low complication rates for an experienced laparoscopic bariatric surgeon without prior robotic skills. Learning curves are steep and operation times can be effectively decreased by increasing the experience of the surgeon.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Humanos , Derivação Gástrica/métodos , Curva de Aprendizado , Centros de Atenção Terciária , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Cirurgia Bariátrica/métodos , Laparoscopia/métodos , Resultado do Tratamento
4.
Clin Exp Metastasis ; 36(1): 57-66, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30680598

RESUMO

Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept® S and Tandem™. Four hours after treatment concentrations of CPT-11 and SN-38 were analyzed in plasma, tumor and liver samples by high-performance liquid chromatography. Additionally, DNA-damage and apoptosis were analyzed immunohistochemically. Tumor tissue concentrations of SN-38 were significantly increased after HAI with irinotecan and EmboCept® S compared to the other groups. The number of apoptotic cells was significantly higher after both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan compared to the control group. HAI with irinotecan and EmboCept® S resulted in an increased SN-38 tumor concentration. Both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan were highly effective with regard to apoptosis.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Artéria Hepática , Irinotecano/administração & dosagem , Irinotecano/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Amido/administração & dosagem , Animais , Apoptose , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Infusões Intra-Arteriais , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Ratos , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/metabolismo , Células Tumorais Cultivadas
5.
J Clin Invest ; 128(7): 3053-3070, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29664738

RESUMO

Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge because, once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury. We identified a protective mechanism controlled by the transcription factor ARNT that effectively inhibits progression of chronic kidney injury by transcriptional induction of ALK3, the principal mediator of antifibrotic and proregenerative bone morphogenetic protein-signaling (BMP-signaling) responses. We further report that ARNT expression itself is controlled by the FKBP12/YY1 transcriptional repressor complex and that disruption of such FKBP12/YY1 complexes by picomolar FK506 at subimmunosuppressive doses increases ARNT expression, subsequently leading to homodimeric ARNT-induced ALK3 transcription. Direct targeting of FKBP12/YY1 with in vivo morpholino approaches or small molecule inhibitors, including GPI-1046, was equally effective for inducing ARNT expression, with subsequent activation of ALK3-dependent canonical BMP-signaling responses and attenuated chronic organ failure in models of chronic kidney disease, and also cardiac and liver injuries. In summary, we report an organ-protective mechanism that can be pharmacologically modulated by immunophilin ligands FK506 and GPI-1046 or therapeutically targeted by in vivo morpholino approaches.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/biossíntese , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/metabolismo , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Linhagem Celular , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pirrolidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tacrolimo/farmacologia , Proteína 1A de Ligação a Tacrolimo/antagonistas & inibidores , Proteína 1A de Ligação a Tacrolimo/metabolismo , Fator de Transcrição YY1/antagonistas & inibidores , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
6.
Clin Oral Investig ; 22(5): 2039-2045, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29243116

RESUMO

BACKGROUND: The aim of this study was to evaluate the oral health-related quality of life (OHRQoL) depending on dental and periodontal health of different patients before and after liver transplantation (pre- and postLTx) compared to a healthy control group (HC). METHODS: OHRQoL was rated using the German short form of Oral Health Impact Profile (OHIP G14). To estimate dental health, the decayed (D-T), missing (M-T), and filled (F-T) teeth index (DMF-T) was used. Periodontal health was classified as healthy/mild, moderate, or severe periodontitis. The following statistics are used: Mann-Whitney U test, Kruskal-Wallis test, chi-square test, and Fisher test (α = 5%). RESULTS: A total of 24 preLTx, 47 postLTx, and 75 HC patients were included. Significant differences in DMF-T, D-T, M-T, and F-T scores were detected between groups (p < 0.001). Prevalence of periodontitis was comparable between groups (p = 0.340). OHRQoL was reduced in pre- and postLTx (OHIP G14 preLTx 4.2 [1.5; 0-4.0], postLTx 4.1 [1; 0-5.0], HC 1.4 [0; 0-2.0]; p = 0.003), without associations to their oral status (p > 0.05). CONCLUSIONS: These preliminary findings show a reduced OHRQoL without associations to their oral status, which might indicate an influence of potential disease-related factors on OHRQoL. Further studies with larger groups are necessary to verify this observation. CLINICAL RELEVANCE: A special dental care of patients before and after LTx is needed, including a comprehensive assessment of the individual patient's OHRQoL.


Assuntos
Transplante de Fígado , Saúde Bucal , Qualidade de Vida , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Índice CPO , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Periodontite/epidemiologia , Prevalência , Inquéritos e Questionários
7.
Int Dent J ; 67(4): 244-251, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28295299

RESUMO

OBJECTIVE: The aim of this single-centre, cross-sectional study was to evaluate dental, periodontal and mycological findings, as well as oral behaviour, in patients before (pre-LTx) and after (post-LTx) liver transplantation. METHODS: A total of 47 patients pre-LTx and 119 patients post-LTx were asked to participate. Oral health behaviour was assessed using a standardised questionnaire. Oral examinations included dental [decayed, missing and filled teeth (DMFT) index] and periodontal [papillary bleeding index (PBI), periodontal probing depth (PPD) and clinical attachment loss (CAL)] findings. For Candida screening, swabs from the oral mucosa were cultured. Statistical analysis was performed using the Student's t-test or the Mann-Whitney U-test, depending on whether or not the data followed a normal distribution; Fisher's exact test was also performed. The significance level was α = 5%. RESULTS: A total of 110 patients were included (pre-LTx, n = 35; post-LTx, n = 75). Different patients were investigated in the post-LTx and pre-LTx groups. Lack of use of supplemental oral-hygiene aids was noted. Between-group comparisons failed to find significant overall differences in DMFT and periodontal status. The post-LTx group showed fewer decayed teeth (P = 0.03). A total of 86% of patients pre-LTx and 84% of patients post-LTx were found to need dental treatment, and 60% of patients pre-LTx and 55% of patients post-LTx showed a need for periodontal treatment. The prevalence of Candida albicans was high; however, there were no statistically significant differences between the groups in regard to fungal infection. CONCLUSION: Improved dental care pre- and post-transplant, including screening for fungal infections, is recommended to avoid systemic infections in LTx patients. Increased attention to oral health care, and interdisciplinary collaboration to provide guidance, is needed to improve the oral health of patients before and after LTx.


Assuntos
Transplante de Fígado , Saúde Bucal , Higiene Bucal , Candidíase Bucal/epidemiologia , Candidíase Bucal/prevenção & controle , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/epidemiologia , Doenças Periodontais/prevenção & controle , Índice Periodontal , Prevalência
8.
Clin Oral Investig ; 21(3): 745-752, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27074844

RESUMO

BACKGROUND: The aim of this single-center cross-sectional study was to detect the prevalence of selected periodontal pathogenic bacteria and active matrix metalloproteinase-8 (aMMP-8) level in patients before (preLTx) and after liver transplantation (postLTx). METHODS: Periodontal pocket depth (PPD) and clinical attachment loss (CAL) were assessed. Subgingival biofilm samples were analyzed using polymerase chain reaction (PCR) to detect 11 common periodontal pathogens. Gingival crevicular fluid (GCF) samples were analyzed with enzyme-linked immunosorbent assay (ELISA) to determine aMMP-8 level and assigned to a scoring system: score 0: 0-8 ng/ml, score 1: 8-20 ng/ml, and score 2: >20 ng/ml. The following were used for the statistical analysis: t test, Mann-Whitney U test, Fishers test (α = 5 %). RESULTS: In total, 110 patients (preLTx: n = 35, postLTx: n = 75) could be included in the study. Periodontal findings were not significantly different between groups. In microbiological analysis, a significantly higher prevalence of Campylobacter rectus in preLTx group was detected (p = 0.03). Significantly more patients with score 0 in postLTx group (p = 0.024) and significantly more patients with score 1 in preLTx group were found (p = 0.004). Furthermore, aMMP-8 concentrations for patients with moderate periodontitis were significantly lower in postLTx group compared to preLTx group (p = 0.045). Additionally, in postLTx group, aMMP-8 concentration was significantly higher in patients with severe periodontitis compared to those with no/mild periodontitis (p = 0.016). CONCLUSION: LTx appears to affect aMMP-8 level, but not bacterial findings in patients after LTx. CLINICAL RELEVANCE: Determination of aMMP-8 level in patients after LTx with immunosuppressive medication might lead to wrong interpretation of the results.


Assuntos
Líquido do Sulco Gengival/química , Transplante de Fígado , Metaloproteinase 8 da Matriz/sangue , Perda da Inserção Periodontal/microbiologia , Bolsa Periodontal/microbiologia , Adulto , Idoso , Biofilmes , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Alemanha , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Reação em Cadeia da Polimerase
9.
BMC Oral Health ; 16(1): 72, 2016 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-27531498

RESUMO

BACKGROUND: Aim of this single center cross-sectional study was to investigate oral behavior, dental, periodontal and microbiological findings in patients undergoing hemodialysis (HD) and after kidney transplantation (KT). METHODS: Patients undergoing HD for end-stage renal failure and after KT were investigated. Oral health behavior was recorded using a standardized questionnaire, e.g. dental behavior, tooth brushing, oral hygiene aids. Oral investigation included screening of oral mucosa, dental findings (DMF-T) and periodontal situation (Papilla bleeding index [PBI] periodontal probing depth [PPD] and clinical attachment loss [CAL]). Additionally, microbiological analysis of subgingival biofilm samples (PCR) was performed. STATISTICAL ANALYSIS: Student's t-test or Mann-Whitney-U-test, Fisher's exact test (α = 5 %). RESULTS: A total of 70 patients (HD: n = 35, KT: n = 35) with a mean age of 56.4 ± 11.1 (HD) and 55.8 ± 10.9 (KT) years were included. Lack in use of additional oral hygiene (dental floss, inter-dental brush) was found. KT group presented significantly more gingivial overgrowth (p = 0.01). DMF-T was 19.47 ± 5.84 (HD) and 17.61 ± 5.81 (KT; p = 0.21). Majority of patients had clinically moderate and severe periodontitis; showing a need for periodontal treatment of 57 % (HD) and 71 % (KT; p = 0.30). Significantly higher prevalence of Parvimonas micra and Capnocytophaga species in the HD group were found (p < 0.01). CONCLUSION: Periodontal treatment need and lack in oral behavior for both groups indicate the necessity of an improved early treatment and prevention of dental and periodontal disease, e.g. in form of special care programs. Regarding microbiological findings, no major differences between KT and HD patients were found.


Assuntos
Placa Dentária , Transplante de Rim , Saúde Bucal , Perda da Inserção Periodontal , Diálise Renal , Adulto , Idoso , Estudos Transversais , Índice de Placa Dentária , Feminino , Humanos , Falência Renal Crônica , Masculino , Pessoa de Meia-Idade , Boca/microbiologia , Índice Periodontal
10.
Dis Colon Rectum ; 59(5): 377-85, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27050599

RESUMO

BACKGROUND: For patients with ycT1/2 rectal carcinomas after neoadjuvant chemoradiotherapy, local excision instead of radical surgery has increasingly been discussed as a way to avoid postoperative morbidity associated with radical surgery. OBJECTIVE: The purpose of this study was to determine the incidence of lymph node metastases in total mesorectal excision specimens with ypT0, ypT1/2, and ypT3/4 rectal cancers. DESIGN: This is a prospective and retrospective cohort study. SETTINGS: This study was conducted in tertiary referral hospitals that are part of the German Rectal Cancer Study Group. PATIENTS: A total of 479 patients with stage II and III rectal cancers treated within phase III trials of the German Rectal Cancer Study Group were evaluated. Specimens from 81 patients treated in the Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society (CAO/ARO/AIO-04) trial were prospectively studied with extensive microscopic screening of the entire mesorectum. The frequency and localization of nodal metastases were specified and compared with those of 398 patients having received neoadjuvant chemoradiation within the CAO/ARO/AIO-94 trial. MAIN OUTCOME MEASURES: Frequency and localization of mesorectal lymph node metastases in patients with ypT0, ypT1/2, or ypT3/4 cancer were measured. RESULTS: A mean number of 28.0 ± 13.7 nodes were detected per specimen within the prospective group. A total of 25% of patients in the ypT1/2 group had nodal metastases compared with 40% in the ypT3/4 group. Patients with node-positive ypT1/2 had a mean number of 2.2 metastases, and 55% of these metastases were located far from the primary lesion in the proximal mesorectum. Within the CAO/ARO/AIO-94 cohort (n = 398), 19% of patients with ypT1/2 (ypT1 = 22%; ypT2 = 18%) had ypN+ status compared with 43% with ypT3/4 cancers (ypT3 = 40%; ypT4 = 73%). LIMITATIONS: Low numbers of patients with ypT0 limited the evaluation of nodal metastases in pathologic complete responders. CONCLUSIONS: Even in good responders (ypT1/2), >20% of rectal carcinomas still harbored residual lymph node metastases. Local excision for patients with ycT1/2 rectal cancers would, thus, miss metastases in a considerable percentage and might involve the risk of significant undertreatment in a number of patients.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Linfonodos/patologia , Terapia Neoadjuvante , Neoplasias Retais/terapia , Reto/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/patologia , Reto/patologia , Estudos Retrospectivos
11.
Oncol Lett ; 11(1): 360-364, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870218

RESUMO

Chemokines and their receptors have been shown to contribute to tumor growth and metastatic spread in various gastrointestinal cancer entities. In the present study, the mRNA expression profiles and clinical significance of chemokine ligand CXCL12 and its corresponding receptor CXCR4 were investigated in patients with gastric cancer (GC). Using quantitative polymerase chain reaction, the expression profile of CXCL12/CXCR4 was analyzed in resection specimens from the patients with GC (n=66) and in corresponding normal gastric tissues. Upon investigating CXCL12/CXCR4 mRNA expression levels in the GC tissues, significant downregulation of CXCL12 expression was demonstrated (P<0.05), whereas CXCR4 mRNA expression was shown to be significantly upregulated (P<0.05). Likewise, in gastric carcinoma patients undergoing neoadjuvant chemotherapy, CXCR4 expression was found to be significantly upregulated (P<0.05), whereas in GC patients with lymph and vein infiltration, CXCL12 mRNA expression was significantly downregulated (P<0.05). These results demonstrate a significant inverse association between the development and progress of GC and CXCL12/CXCR4 mRNA expression. CXCR4 mRNA upregulation was promoted under the effect of neoadjuvant chemotherapy prior to surgery in GC patients, whereas higher tumor stages with lymph and vein infiltration negatively affected CXCL12 mRNA expression.

12.
Oncol Rep ; 30(3): 1285-92, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23817679

RESUMO

Recently, we reported a functional interaction between miR-21 and its identified chemokine target CCL20 in colorectal cancer (CRC) cell lines. Here, we investigated whether such functional interactions are permitted at the cellular level which would require an inverse correlation of expression and also co-expression of miR-21 and CCL20 in the same cell. Expression profiling was performed using qPCR, and ELISA, in situ hybridization and immunohistochemistry were applied for the presentation of their cellular localization. We demonstrated that miR-21 as well as CCL20 were both significantly upregulated in CRC tissues; thus, showing no antidromic expression pattern. This provided an initial clue that miR-21 and CCL20 may not be expressed in the same cell. In addition, we located miR-21 expression at the cellular level predominantly in stromal cells such as tumor-associated fibroblasts and to a minor degree in immune cells such as macrophages and lymphocytes. Likewise, CCL20 expression was primarily detected in tumor-infiltrating immune cells. Thus, investigating the cellular localization of miR-21 and its target CCL20 revealed that both molecules are expressed predominantly in the microenvironment of CRC tumors.


Assuntos
Quimiocina CCL20/metabolismo , Neoplasias Colorretais/genética , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Células Estromais/metabolismo , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Quimiocina CCL20/genética , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/patologia , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/patologia
13.
Int J Antimicrob Agents ; 39(6): 505-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22526014

RESUMO

Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis.


Assuntos
Anti-Infecciosos/farmacocinética , Antibioticoprofilaxia , Compostos Aza/farmacocinética , Neoplasias Hepáticas/cirurgia , Fígado/metabolismo , Quinolinas/farmacocinética , Adulto , Idoso , Anti-Infecciosos/sangue , Anti-Infecciosos/uso terapêutico , Compostos Aza/sangue , Compostos Aza/uso terapêutico , Feminino , Fluoroquinolonas , Humanos , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Quinolinas/sangue , Quinolinas/uso terapêutico , Resultado do Tratamento , Adulto Jovem
14.
J Gastrointest Surg ; 16(6): 1240-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22258872

RESUMO

INTRODUCTION: Midoesophageal diverticula >4cm in size are a medical rarity with a dozen reported cases so far. Usually, midoesophageal diverticula tend to be of small size and asymptomatic. CASE REPORT: We herein present a case of a woman suffering from a midoesophageal diverticulum in a very large dimension--never described in the current literature before--who successfully underwent surgical resection via thoracotomy. DISCUSSION: If symptomatic, common symptoms are dysphagia and regurgitation. The risk of malignant transformation is low. Treatment of midoesophageal diverticula is based on size and symptoms of the patient. Asymptomatic or small diverticula detected during routine endoscopy can be followed-up without further therapy, whereas symptomatic or large diverticula should be treated surgically by resection. Myotomy should be performed if any motility disorder is evident. Open as well as minimal invasive approach by thoracoscopical surgery is both feasible.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Divertículo Esofágico/diagnóstico , Idoso , Diagnóstico Diferencial , Divertículo Esofágico/cirurgia , Endoscopia Gastrointestinal , Feminino , Seguimentos , Humanos , Índice de Gravidade de Doença , Toracotomia/métodos , Tomografia Computadorizada por Raios X
15.
J Pediatr Surg ; 46(9): e21-4, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21929971

RESUMO

A 15-year-old adolescent boy with autosomal recessive agammaglobulinemia underwent endoscopy because of unexplained growth failure and malnutrition. Esophagogastroduodenoscopy revealed antropyloric stenosis, and a biopsy showed an invasive gastric adenocarcinoma. Chronic atrophic corpus gastritis type A and Helicobacter pylori were also identified. Abdominal magnetic resonance imaging confirmed the stenosis resulting from a semicircular intramural tumor without obvious local or distant metastatic spread. Gastrectomy with an extended lymphadenectomy was performed. Esophagoduodenal continuity was restored by an interposed jejunal parallel pouch developed from the first jejunal loop. Oral feeding was supplemented by parenteral nutrition via a Broviac catheter, and the patient is well 4 months later. Several cases of gastric cancer have been reported in children with hereditary agammaglobulinemia. Thus, endoscopy is mandatory in such patients with gastrointestinal symptoms to identify and treat tumors before metastasis occurs. Total gastrectomy, extended lymphadenectomy, and reconstruction using a jejunal reservoir with maintenance of duodenal continuity should be considered.


Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Agamaglobulinemia/complicações , Gastrectomia , Jejuno/cirurgia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Estômago/cirurgia , Estruturas Criadas Cirurgicamente , Adolescente , Humanos , Masculino , Peristaltismo
16.
J Anal Toxicol ; 33(4): 190-7, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19470220

RESUMO

1-(4-Methylphenyl)-2-pyrrolidin-1-ylhexan-1-one (4'-methyl-alpha-pyrrolidinohexanophenone, MPHP) is a new designer drug that appeared on the illicit drug market. It is mainly metabolized to 4'-hydroxymethyl-alpha-pyrrolidinohexanophenone (HO-MPHP) followed by oxidation to the respective carboxylic acid. For studies on the quantitative involvement of human cytochrome P450 (CYP) isoenzymes in the initial hydroxylation, a reference standard of HO-MPHP was needed. Therefore, the aim of this study was to synthesize this metabolite using a biotechnological approach. MPHP.HNO(3) (250 micromol) was incubated with 1 L culture of the fission yeast (Schizosaccharomyces pombe) strain CAD64 heterologously co-expressing human CYP reductase and CYP2D6. After centrifugation, the product was isolated from the incubation supernatants by solid-phase extraction. Further product cleanup was achieved by semi-preparative high-performance liquid chromatography (HPLC). After extraction of HO-MPHP from the respective eluent fractions, it was precipitated as its hydrochloric salt. The final product HO-MPHP.HCl was obtained in a yield of 138 micromol (43 mg, 55%). Its identity was confirmed by full scan gas chromatography-mass spectrometry (after trimethylsilylation), (1)H-NMR, and (13)C-NMR. The product purity as estimated from HPLC-ultraviolet analysis was greater than 99%. The described biotechnological approach proved to be a versatile alternative to the chemical synthesis of HO-MPHP.


Assuntos
Butirofenonas/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Drogas Desenhadas/metabolismo , Pirrolidinas/metabolismo , Schizosaccharomyces/enzimologia , Biotransformação , Butirofenonas/química , Butirofenonas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP2D6/genética , Drogas Desenhadas/química , Cromatografia Gasosa-Espectrometria de Massas , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Humanos , Hidroxilação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Pirrolidinas/química , Pirrolidinas/isolamento & purificação , Proteínas Recombinantes/metabolismo , Schizosaccharomyces/genética , Espectrofotometria Ultravioleta
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