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1.
Methods Mol Biol ; 2288: 113-126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270008

RESUMO

Carrot is a vegetable of increasing economic importance. New hybrid cultivars are constantly required to meet the changing market needs. The application of anther culture significantly shortens the difficult and long-lasting breeding of carrot. We examined all the stages of the process of generating androgenic plants: induction of embryos in anther cultures, regeneration and acclimatization of produced plants, their evaluation, ploidy and homozygosity, and many other factors affecting their effectiveness. Every factor has been optimized by experimentally selecting the optimal level. As a result, a full protocol of producing homozygous plants using anther cultures was developed, which is presented in this chapter.


Assuntos
Daucus carota/crescimento & desenvolvimento , Daucus carota/genética , Melhoramento Vegetal/métodos , Aclimatação/genética , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/fisiologia , Meios de Cultura/química , Daucus carota/fisiologia , Flores/genética , Flores/crescimento & desenvolvimento , Heterozigoto , Homozigoto , Isoenzimas/análise , Biologia Molecular/métodos , Regeneração/genética , Técnicas de Cultura de Tecidos
2.
Methods Mol Biol ; 2289: 301-312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270079

RESUMO

Hybrid varieties dominate the red beet market. The breeding process necessary to produce these cultivars is very difficult and time consuming. The application of in vitro gynogenesis can reduce the time needed to produce the corresponding homozygous pure lines to a few months. Our research team has developed a method to obtain red beet doubled haploid plants by gynogenesis. The best medium for gynogenesis induction is the B5 medium with the addition of 0.5 mg/L IAA, 0.2 mg/L BA, and 322 mg/L putrescine, whereas the best medium for shoot induction from embryos proved to be the MS medium supplemented with 0.1 mg/L NAA, 0.1 mg/L BA, and 0.5 mg/L putrescine. The shoots obtained were rooted on MS medium containing half the concentration of microelements and 3 mg/L NAA, 160 mg/L putrescine, and 20 g/L sucrose. Ploidy evaluation of gynogenetic plants was performed by flow cytometry and homozygosity or heterozygosity was determined by two isoenzymatic systems: PGI and AAT.


Assuntos
Beta vulgaris/efeitos dos fármacos , Óvulo Vegetal/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Haploidia , Homozigoto , Melhoramento Vegetal/métodos , Regeneração/efeitos dos fármacos
3.
Clin Transl Sci ; 14(3): 784-790, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33421282

RESUMO

Although traditional approaches to biomarker discovery have elucidated key molecular markers that have improved drug selection (precision medicine), the discovery of biomarkers that inform optimal dose selection (precision dosing) continues to be a challenge in many therapeutic areas. Larger and more diverse study populations are necessary to discover additional biomarkers that provide the resolution needed for a more tailored dose. To generate and accommodate large datasets of drug response phenotypes, time- and cost-efficient strategies are necessary. In particular, a multitude of technological advances that originated for purposes outside of biomedical research (electronic health records, direct-to-consumer genetic testing, social media, mobile devices, and machine learning) have made it easier to communicate, connect, and gather information from consumers. Although these technologies have been used with success in the health sciences for an array of purposes, these resources have not been fully capitalized on for precision dosing. This perspective will touch on how these innovations can be used as data sources, data collection tools, and data processing tools for drug-response phenotypes with a unique focus on advancing biomarker-driven precision dosing.

4.
Surg Endosc ; 35(4): 1749-1754, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32314078

RESUMO

BACKGROUND: Symptomatic rectal stump leakage (RSL) is a serious complication after discontinuity resection and requires immediate surgical, interventional, or endoscopic therapy. Re-operations are associated with high morbidity and mortality in these mostly very ill patients. Endoscopic vacuum therapy (EVT) has been established for management of anastomotic leakage; however, its effectiveness for RSL treatment has not been analyzed in detail yet. METHODS: A retrospective analysis of patients treated with EVT for RSL between 2001 and 2018 analyzing factors predicting therapy success and duration was carried out. RESULTS: Fifty-six patients with RSL at a median age of 66 years were included. Of these, 18 patients (32%) had been referred for EVT from external departments or institutions. RSL was associated with a relevant clinical deterioration in all patients, and 55 patients (98%) had been classified as ASA 3 and 4, preoperatively. In 9 patients (16%), additional surgical revision was necessary with initiation of EVT. In 47 patients (84%), EVT was successful and local control of the inflammatory focus was achieved. The median duration of therapy was 20 days. Two patients (4%) suffered from minor EVT-associated bleeding that was endoscopically controlled. Preoperative radiation of the pelvis was significantly associated with EVT failure (P = 0.035), whereas patient age represented a predictive factor for therapy length (P = 0.039). In 12 patients (21%), restoration of intestinal continuity was achieved in the further course. CONCLUSIONS: We present the first specific series on EVT for RSL. EVT for RSL was shown to be an effective and safe minimal-invasive treatment option, avoiding surgical revision in the majority of patients.

5.
Surg Endosc ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259019

RESUMO

BACKGROUND: Evidence for endoscopic vacuum therapy (EVT) for colorectal defects is still based on small patient series from various institutions, employing different treatment algorithms and methods. As EVT was invented at our institution 20 years ago, the aim was to report the efficacy and safety of EVT for colorectal defects as well as to analyze factors associated with efficacy, therapy duration, and outpatient treatment. METHODS: Cohort study with analysis of prospectively collected data of patients receiving EVT for colorectal defects at a tertiary referral center in Germany (n = 281). RESULTS: The majority of patients had malignant disease (83%) and an American Society of Anesthesiologists classification of III/IV (81%). Most frequent indications for EVT were anastomotic leakage after sigmoid or rectal resection (67%) followed by rectal stump leakage (20%). EVT was successful in 256 out of 281 patients (91%). EVT following multi-visceral resection (P = 0.037) and recent surgical revision after primary surgery (P = 0.009) were risk factors for EVT failure. EVT-associated adverse events occurred in 27 patients (10%). Median treatment duration was 25 days. Previous chemo-radiation (P = 0.006) was associated with a significant longer duration of EVT. Outpatient treatment was conducted in 49% of patients with a median hospital stay reduction of 15 days and 98% treatment success. Younger patient age (P = 0.044) was associated with the possibility of outpatient treatment. Restoration of intestinal continuity was achieved in 60% of patients where technically possible with a 12-month rate of 52%. CONCLUSIONS: In patients with colorectal defects, EVT appears to be a safe and effective, minimally invasive option for in- and outpatient treatment.

6.
Front Plant Sci ; 11: 103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174931

RESUMO

An improvement in photosynthetic rate promotes the growth of crop plants. The sink-regulation of photosynthesis is crucial in optimizing nitrogen fixation and integrating it with carbon balance. Studies on these processes are essential in understanding growth inhibition in plants with ammonium ( NH 4 + ) syndrome. Hence, we sought to investigate the effects of using nitrogen sources with different states of reduction (during assimilation of NO 3 - versus NH 4 + ) on the photosynthetic performance of Arabidopsis thaliana. Our results demonstrated that photosynthetic functioning during long-term NH 4 + nutrition was not disturbed and that no indication of photoinhibition of PSII was detected, revealing the robustness of the photosynthetic apparatus during stressful conditions. Based on our findings, we propose multiple strategies to sustain photosynthetic activity during limited reductant utilization for NH 4 + assimilation. One mechanism to prevent chloroplast electron transport chain overreduction during NH 4 + nutrition is for cyclic electron flow together with plastid terminal oxidase activity. Moreover, redox state in chloroplasts was optimized by a dedicated type II NAD(P)H dehydrogenase. In order to reduce the amount of energy that reaches the photosynthetic reaction centers and to facilitate photosynthetic protection during NH 4 + nutrition, non-photochemical quenching (NPQ) and ample xanthophyll cycle pigments efficiently dissipate excess excitation. Additionally, high redox load may be dissipated in other metabolic reactions outside of chloroplasts due to the direct export of nucleotides through the malate/oxaloacetate valve. Mitochondrial alternative pathways can downstream support the overreduction of chloroplasts. This mechanism correlated with the improved growth of A. thaliana with the overexpression of the alternative oxidase 1a (AOX1a) during NH 4 + nutrition. Most remarkably, our findings demonstrated the capacity of chloroplasts to tolerate NH 4 + syndrome instead of providing redox poise to the cells.

7.
Int J Mol Sci ; 19(8)2018 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-30060552

RESUMO

For optimal plant growth, carbon and nitrogen availability needs to be tightly coordinated. Mitochondrial perturbations related to a defect in complex I in the Arabidopsis thalianafrostbite1 (fro1) mutant, carrying a point mutation in the 8-kD Fe-S subunit of NDUFS4 protein, alter aspects of fundamental carbon metabolism, which is manifested as stunted growth. During nitrate nutrition, fro1 plants showed a dominant sugar flux toward nitrogen assimilation and energy production, whereas cellulose integration in the cell wall was restricted. However, when cultured on NH4⁺ as the sole nitrogen source, which typically induces developmental disorders in plants (i.e., the ammonium toxicity syndrome), fro1 showed improved growth as compared to NO3- nourishing. Higher energy availability in fro1 plants was correlated with restored cell wall assembly during NH4⁺ growth. To determine the relationship between mitochondrial complex I disassembly and cell wall-related processes, aspects of cell wall integrity and sugar and reactive oxygen species signaling were analyzed in fro1 plants. The responses of fro1 plants to NH4⁺ treatment were consistent with the inhibition of a form of programmed cell death. Resistance of fro1 plants to NH4⁺ toxicity coincided with an absence of necrotic lesion in plant leaves.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Parede Celular/metabolismo , NADH Desidrogenase/metabolismo , Nitrogênio/metabolismo , Açúcares/metabolismo , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Morte Celular , Parede Celular/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , NADH Desidrogenase/genética , Nitratos/metabolismo , Mutação Puntual , Espécies Reativas de Oxigênio/metabolismo
8.
J Surg Case Rep ; 2018(4): rjy074, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29713447

RESUMO

A 25-year-old male Syrian refugee presented in our hospital with recurrent hip infections after having undergone hip arthroplasty abroad following destruction of his right hip joint by shell splinters in the Syrian civil war. The patient underwent hip arthroplasty revision with implantation of a cement spacer. CT-scan with rectal contrast media filling revealed a recto-acetabular fistula. Consecutively, the patient underwent ileostomy formation. The fistula was then successfully closed by endoscopic over-the-scope clipping (OTSC®). Fistulas between intestines and joints rarely develop and in the few cases published mostly extensive abdominal rescue surgery has been performed. Here, we present a case of a traumatic recto-acetabular fistula that was successfully closed by OTSC. This innovative method could represent a safe and suitable option to effectively close fistulas between joints and intestines thereby avoiding extensive rescue surgery with bowel resection or permanent ostomy.

9.
Int J Mol Sci ; 19(5)2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29747392

RESUMO

Environmental stresses, including ammonium (NH4⁺) nourishment, can damage key mitochondrial components through the production of surplus reactive oxygen species (ROS) in the mitochondrial electron transport chain. However, alternative electron pathways are significant for efficient reductant dissipation in mitochondria during ammonium nutrition. The aim of this study was to define the role of external NADPH-dehydrogenase (NDB1) during oxidative metabolism of NH4⁺-fed plants. Most plant species grown with NH4⁺ as the sole nitrogen source experience a condition known as “ammonium toxicity syndrome”. Surprisingly, transgenic Arabidopsis thaliana plants suppressing NDB1 were more resistant to NH4⁺ treatment. The NDB1 knock-down line was characterized by milder oxidative stress symptoms in plant tissues when supplied with NH4⁺. Mitochondrial ROS accumulation, in particular, was attenuated in the NDB1 knock-down plants during NH4⁺ treatment. Enhanced antioxidant defense, primarily concerning the glutathione pool, may prevent ROS accumulation in NH4⁺-grown NDB1-suppressing plants. We found that induction of glutathione peroxidase-like enzymes and peroxiredoxins in the NDB1-surpressing line contributed to lower ammonium-toxicity stress. The major conclusion of this study was that NDB1 suppression in plants confers tolerance to changes in redox homeostasis that occur in response to prolonged ammonium nutrition, causing cross tolerance among plants.


Assuntos
Compostos de Amônio/toxicidade , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/fisiologia , Glutationa/metabolismo , NADPH Desidrogenase/metabolismo , Antioxidantes/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Ácido Ascórbico/metabolismo , Biomarcadores/metabolismo , Respiração Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Modelos Biológicos , Nitratos/farmacologia , Nucleotídeos/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Fosforilação/efeitos dos fármacos , Plantas Geneticamente Modificadas , Piridinas , Espécies Reativas de Oxigênio/metabolismo
11.
Front Plant Sci ; 8: 1353, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28878783

RESUMO

Reactive oxygen species (ROS), by their very nature, are highly reactive, and it is no surprise that they can cause damage to organic molecules. In cells, ROS are produced as byproducts of many metabolic reactions, but plants are prepared for this ROS output. Even though extracellular ROS generation constitutes only a minor part of a cell's total ROS level, this fraction is of extraordinary importance. In an active apoplastic ROS burst, it is mainly the respiratory burst oxidases and peroxidases that are engaged, and defects of these enzymes can affect plant development and stress responses. It must be highlighted that there are also other less well-known enzymatic or non-enzymatic ROS sources. There is a need for ROS detoxification in the apoplast, and almost all cellular antioxidants are present in this space, but the activity of antioxidant enzymes and the concentration of low-mass antioxidants is very low. The low antioxidant efficiency in the apoplast allows ROS to accumulate easily, which is a condition for ROS signaling. Therefore, the apoplastic ROS/antioxidant homeostasis is actively engaged in the reception and reaction to many biotic and abiotic stresses.

12.
Front Plant Sci ; 8: 1344, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28848567

RESUMO

Plants mainly utilize inorganic forms of nitrogen (N), such as nitrate (NO3-) and ammonium (NH4+). However, the composition of the N source is important, because excess of NH4+ promotes morphological disorders. Plants cultured on NH4+ as the sole N source exhibit serious growth inhibition, commonly referred to as "ammonium toxicity syndrome." NH4+-mediated suppression of growth may be attributable to both repression of cell elongation and reduction of cell division. The precondition for cell enlargement is the expansion of the cell wall, which requires the loosening of the cell wall polymers. Therefore, to understand how NH4+ nutrition may trigger growth retardation in plants, properties of their cell walls were analyzed. We found that Arabidopsis thaliana using NH4+ as the sole N source has smaller cells with relatively thicker cell walls. Moreover, cellulose, which is the main load-bearing polysaccharide revealed a denser assembly of microfibrils. Consequently, the leaf blade tissue showed elevated tensile strength and indicated higher cell wall stiffness. These changes might be related to changes in polysaccharide and ion content of cell walls. Further, NH4+ toxicity was associated with altered activities of cell wall modifying proteins. The lower activity and/or expression of pectin hydrolyzing enzymes and expansins might limit cell wall expansion. Additionally, the higher activity of cell wall peroxidases can lead to higher cross-linking of cell wall polymers. Overall, the NH4+-mediated inhibition of growth is related to a more rigid cell wall structure, which limits expansion of cells. The changes in cell wall composition were also indicated by decreased expression of Feronia, a receptor-like kinase involved in the control of cell wall extension.

13.
Physiol Plant ; 160(1): 65-83, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28008622

RESUMO

Plants can assimilate nitrogen from soil pools of both ammonium and nitrate, and the relative levels of these two nitrogen sources are highly variable in soil. Long-term ammonium nutrition is known to cause damage to Arabidopsis that has been linked to mitochondrial oxidative stress. Using hydroponic cultures, we analysed the consequences of rapid shifts between nitrate and ammonium nutrition. This did not induce growth retardation, showing that Arabidopsis can compensate for the changes in redox metabolism associated with the variations in nitrogen redox status. During the first 3 h of ammonium treatment, we observed distinct transient shifts in reactive oxygen species (ROS), low-mass antioxidants, ROS-scavenging enzymes, and mitochondrial alternative electron transport pathways, indicating rapid but temporally separated changes in chloroplastic, mitochondrial and cytosolic ROS metabolism. The fast induction of antioxidant defences significantly lowered intracellular H2 O2 levels, and thus protected Arabidopsis leaves from oxidative stress. On the other hand elevated extracellular ROS production in response to ammonium supply may be involved in signalling. The response pattern displays an intricate plasticity of Arabidopsis redox metabolism to minimise stress in responses to nutrient changes.


Assuntos
Compostos de Amônio/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Antioxidantes/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Nitratos/metabolismo , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Artigo em Inglês | MEDLINE | ID: mdl-27965838

RESUMO

BACKGROUND: Neoadjuvant chemotherapy is a standard of care for patients with adenocarcinoma of the esophagus and stomach in Europe, but still only 20-40 % respond to therapy and the critical issue; how to treat nonresponding patients is still unclear. So far, there is no randomized trial evaluating the impact of early termination of neoadjuvant chemotherapy and immediate tumor resection in nonresponding patients with locally advanced gastroesophageal cancer on postoperative outcome. With this exploratory pilot trial, we want to get first estimates about the effect of discontinuation of chemotherapy with the aim to plan and conduct a further definitive trial. METHODS/DESIGN: OPTITREAT is designed as a single-center, randomized controlled pilot trial with two parallel study groups. Four weeks after starting neoadjuvant chemotherapy in all patients, clinical response will be assessed by endoscopy and endosonographic ultrasound. Then, nonresponding patients (n = 84) will be randomized in a 1:1 ratio to intervention group with stopping chemotherapy and immediate tumor resection or control group with completion of chemotherapy before surgery. Outcome measures are overall survival, R0 resection rate, perioperative morbidity and mortality, histopathological response, and quality of life. Statistical analysis will be based on the intention-to-treat population. Due to the study design as an explorative pilot trial, no formal sample size calculation was performed. The planned total sample size of 120 patients is considered ethical and large enough to show the feasibility and safety of the concept. First data on differences between the study groups in the defined endpoints will also be generated. DISCUSSION: Individualized therapy is of utmost interest in the treatment of locally advanced gastroesophageal adenocarcinoma as less than half of the patients show objective response to current chemotherapy regimens. The findings of the OPTITREAT trial will help to get first data about clinical response evaluation followed by immediate tumor resection in nonresponding patients after 4 weeks of neoadjuvant chemotherapy. Based on the results of this pilot study, a future confirmatory trial will be planned to prove efficacy and evaluate significance. TRIAL REGISTRATION: German Clinical Trial Register number: DRKS00004668.

15.
Gastric Cancer ; 18(2): 314-25, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24722800

RESUMO

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. METHODS: Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. RESULTS: In A, 479 patients (70%) were defined as clinical nonresponders, 207 (30%) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p < 0.001). Clinical and histopathological response correlated significantly (p < 0.001). In multivariate analysis, clinical response was an independent prognostic factor (HR for death 1.4, 95% CI 1.0-1.8, p = 0.032). In B, 140 patients (76%) were nonresponders and 44 (24%) responded. Median survival was 33 months, (nonresponders: 27 months, responders: not reached, p = 0.003). Interim clinical response evaluation (118 patients) also had prognostic impact (p = 0.008). Interim, preoperative clinical response and histopathological response correlated strongly (p < 0.001). CONCLUSION: Preoperative clinical response was an independent prognostic factor in center A, while in center B its prognostic value could only be confirmed in univariate analysis. The accordance with histopathological response was good in both centers, and interim clinical response evaluation showed comparable results to preoperative evaluation.


Assuntos
Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Endoscopia/métodos , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Junção Esofagogástrica/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
16.
Langenbecks Arch Surg ; 400(1): 9-18, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25408482

RESUMO

BACKGROUND: Esophagectomy for esophageal cancer remains a challenge with relatively high morbidity. We analyzed outcome, complications, and mortality after abdominothoracic esophagectomy with intrathoracic anastomosis. No routine preoperative risk stratification was performed. METHODS: One hundred eighty-seven consecutive patients (105 AEG I, 21 AEG II, 58 SCC, and 3 other entities) underwent standardized right abdominothoracic esophagectomy with intrathoracic anastomosis and two field lymphadenectomy between 2003 and 2009. Reconstruction was performed mostly with a gastric tube (n = 126) or a fundus rotation gastroplasty (n = 57). Seventy-four patients underwent neoadjuvant treatment (36 patients chemotherapy; 38 patients chemoradiotherapy). RESULTS: Postoperative morbidity was high (73.2 %). Ninety-two patients (49.2 %) suffered from surgical complications, 50 patients had major (26.7 %), and 42 minor (22.5 %) complications. Thirty-day mortality was 9/187 (4.8 %) while in-hospital mortality was doubled with 9.6 %. Six of 19 of the patients died without surgical complications. Preoperative treatment did not increase morbidity or mortality. Surgical complications with subsequent death were tracheobronchial fistula (2/3), ischemia of the gastric tube (3/6), anastomotic leakage (6/30), chylothorax (1/6), and intraoperative bleeding from the aorta (1/1). The median overall survival was 25.0 months. The occurrence of surgical or medical complications did not influence overall survival. In multivariate analysis, cT-category, pN-category, R-category, and re-intubation were independent prognostic factors. CONCLUSIONS: Abdominothoracic esophagectomy with intrathoracic anastomosis without preoperative patient selection is associated with a high risk for complications and subsequent death but ranges still within the upper range of published data. Strict patient selection is accepted to reduce postoperative morbidity and mortality but excludes a subgroup of patients from potentially curative resection.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Junção Esofagogástrica , Excisão de Linfonodo/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/métodos , Comorbidade , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Medição de Risco
17.
Ann Surg Oncol ; 21(5): 1739-48, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24419755

RESUMO

BACKGROUND: Recent data suggest primary resection as the preferable approach in patients with signet ring cell gastric cancer (SRC). The aim of our retrospective exploratory study was to evaluate the influence of SRC on prognosis and response in esophagogastric adenocarcinoma treated with neoadjuvant chemotherapy. METHODS: A total of 723 locally advanced esophagogastric adenocarcinomas (cT3/4 N any) documented in a prospective database from two academic centers were classified according to the WHO definition for SRC (more than 50 % SRC) and analyzed for their association with response and prognosis after neoadjuvant treatment. RESULTS: A total of 235 tumors (32.5 %) contained SRC. Median survival of SRC was 26.3 compared with 46.6 months (p < 0.001) for non-SRC. SRC were significantly associated with female gender, gastric localization, advanced ypT and R1/2 categories, and lower risk of surgical complications and anastomotic leakage (each p < 0.001). Clinical (21.1 vs. 33.7 %, p = 0.001) and histopathological response (less than 10 % residual tumor: 16.3 vs. 28.9 %, p < 0.001) were significantly less frequent in SRC. Clinical response (p = 0.003) and complete histopathological response (pCR) (3.4 %) (p = 0.003) were associated with improved prognosis in SRC. Clinical response, surgical complications, ypTN categories, but not SRC were independent prognostic factors in forward Cox regression analysis in R0 resected patients. Risk of peritoneal carcinomatosis was increased (p < 0.001), while local (p = 0.015) and distant metastases (p = 0.02) were less frequent than in non-SRC. CONCLUSIONS: Prognosis of SRC is unfavorable. Although response to neoadjuvant chemotherapy is rare in SRC, it is associated with improved outcome. Thus, chemotherapy might not generally be abandoned in SRC. A stratification based on SRC should be included in clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células em Anel de Sinete/terapia , Neoplasias Esofágicas/terapia , Esofagectomia , Junção Esofagogástrica/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Terapia Neoadjuvante , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
18.
Gastric Cancer ; 17(3): 478-88, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23996162

RESUMO

BACKGROUND: Neoadjuvant chemotherapy for locally advanced gastric cancer leads to major histopathological response in less than 30 % of patients. Data on interim endoscopic response assessment do not exist. This exploratory prospective study evaluates early endoscopy after 50 % of the chemotherapy as predictor for later response and prognosis. METHODS: Forty-seven consecutive patients were included (45 resected; 33 R0 resections). All patients received baseline endoscopy and CT scans, after 50 % of their chemotherapy (EGD-1, CT-1) and after completion of chemotherapy (EGD-2, CT-2). Interim endoscopic response (EGD-1) was assessed after having received 50 % (6 weeks) of the planned 12 weeks of neoadjuvant chemotherapy. Post-chemotherapy response was clinically assessed by a combination of CT scan (CT-2) and endoscopy (EGD-2). Histopathological response was determined by a standardized scoring system (Becker criteria). Endoscopic response was defined as a reduction of >75 % of the tumor mass. RESULTS: Twelve patients were responders at EGD-1 and 13 at EGD-2. Nine patients (19.1 %) were clinical responders and 7 patients (15.6 %) were histopathological responders after chemotherapy. Specificity, accuracy, and negative predictive value of the interim EGD-1 for subsequent histopathological response were 31/38 (82 %), 36/47 (76 %), and 31/33 (93 %); and for recurrence or death, 28/30 (93.3 %), 38/47 (80.9 %), and 28/35 (80.0 %). Response at EGD-1 was significantly associated with histopathological response (p = 0.010), survival (p < 0.001), and recurrence-free survival (p = 0.009). CONCLUSIONS: Interim endoscopy after 6 weeks predicts response and prognosis. Therefore, tailoring treatment according to interim endoscopic assessment could be feasible, but the findings of this study should be validated in a larger patient cohort.


Assuntos
Antineoplásicos/uso terapêutico , Gastroscopia/métodos , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
19.
Haematologica ; 97(11): 1674-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22689672

RESUMO

Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and nonrelapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.


Assuntos
Endotélio Vascular/metabolismo , Doença Enxerto-Hospedeiro , Enteropatias , Esteroides/administração & dosagem , Trombomodulina/biossíntese , Intervalo Livre de Doença , Endotélio Vascular/patologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Enteropatias/tratamento farmacológico , Enteropatias/metabolismo , Enteropatias/mortalidade , Enteropatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo
20.
Clin Gastroenterol Hepatol ; 7(4): 389-96, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19049832

RESUMO

BACKGROUND & AIMS: A new fluoroscopy-free training system for endoscopic retrograde cholangiopancreatography (ERCP) with different model subtypes recently was developed. This study aimed to establish construct validity by investigating whether the X-Vision ERCP Training System could distinguish experienced endoscopists from beginners and to reveal characteristic mistakes during sphincterotomy. METHODS: Six staff gastroenterologists that practice ERCP, 10 trainees that perform esophagogastroduodenoscopy and colonoscopy, and 12 residents without endoscopic experience each sequentially attempted 4 different models, simulating selective cannulation of the pancreatic or bile duct, intubation of differently arranged rubber papillas, stent placement, and sphincterotomy of a biopapilla. Performance parameters were recorded and participants' expectations were compared before and after training to determine whether the simulator was a credible tool for ERCP training. Staff gastroenterologists graded the realism and utility of the simulation. The quality of sphincterotomy was assessed by an expert endoscopist. RESULTS: Participants with ERCP experience had significantly shorter procedure times compared with those with intermediate (P < .001) or no endoscopic experience (P < .001). Total and single credibility scores significantly increased after simulator practice. The faculty found the X-Vision ERCP Training System to be realistic and useful for training. In the less-experienced groups, common mistakes made during sphincterotomy included inadequate positioning of the duodenoscope, traumatic intubation of the papilla, and continued cutting despite insufficient endoscopic view. CONCLUSIONS: The X-Vision ERCP Training System distinguished subjects with different levels of experience and was regarded as realistic and useful for ERCP training. Common mistakes during sphincterotomy could be assessed objectively.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Esfinterotomia Endoscópica/métodos , Ensino/métodos , Simulação por Computador , Humanos
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