RESUMO
The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.
Assuntos
Adenocarcinoma , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/diagnóstico , Células Neoplásicas Circulantes/patologia , Biópsia Líquida/métodos , Biomarcadores Tumorais , Volume Sanguíneo , Neoplasias PancreáticasRESUMO
BACKGROUND: Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity. METHODS: Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior. RESULTS: One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: - 1079; 95% CI - 2157 to - 1; p = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life. CONCLUSIONS: Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed. TRIAL REGISTRATION: DRKS-ID: DRKS00020499 ; Registered 17 March 2020.
Assuntos
Neoplasias , Qualidade de Vida , Masculino , Humanos , Proteína C-Reativa , Retroalimentação , Exercício Físico , Terapia por Exercício , Neoplasias/cirurgia , OxigênioRESUMO
PURPOSE: Anastomotic leakage (AL) and surgical site infection (SSI) account for most postoperative complications in colorectal surgery. The aim of this retrospective trial was to investigate whether perioperative selective decontamination of the digestive tract (SDD) reduces these complications and to provide a cost-effectiveness model for elective colorectal surgery. METHODS: All patients operated between November 2016 and March 2020 were included in our analysis. Patients in the primary cohort (PC) received SDD and those in the historical control cohort (CC) did not receive SDD. In the case of rectal/sigmoid resection, SDD was also applied via a transanally placed Foley catheter (TAFC) for 48 h postoperatively. A propensity score-matched analysis was performed to identify risk factors for AL and SSI. Costs were calculated based on German diagnosis-related group (DRG) fees per case. RESULTS: A total of 308 patients (154 per cohort) with a median age of 62.6 years (IQR 52.5-70.8) were analyzed. AL was observed in ten patients (6.5%) in the PC and 23 patients (14.9%) in the CC (OR 0.380, 95% CI 0.174-0.833; P = 0.016). SSI occurred in 14 patients (9.1%) in the PC and 30 patients in the CC (19.5%), representing a significant reduction in our SSI rate (P = 0.009). The cost-effectiveness analysis showed that SDD is highly effective in saving costs with a number needed to treat of 12 for AL and 10 for SSI. CONCLUSION: SDD significantly reduces the incidence of AL and SSI and saves costs for the general healthcare system.
Assuntos
Fístula Anastomótica , Cirurgia Colorretal , Idoso , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Antibacterianos/uso terapêutico , Descontaminação , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Trato Gastrointestinal , Humanos , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).
Assuntos
Hemostasia Cirúrgica/métodos , Artéria Hepática/cirurgia , Ligamentos/cirurgia , Pancreaticoduodenectomia/métodos , Hemorragia Pós-Operatória/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/efeitos adversosRESUMO
BACKGROUND: Pelvic exenteration (PE) is the only option for long-term cure of advanced cancer originating from different types of tumor or recurrent disease in the lower pelvis. The aim was to show differences between colorectal and non-colorectal cancer in survival and postoperative morbidity. METHODS: Retrospective data of 63 patients treated with total pelvic exenteration between 2013 and 2018 are reported. Pre-, intra-, and postoperative parameters, survival data, and risk factors for complications were analyzed. RESULTS: A total of 57.2% (n = 37) of the patients had colorectal cancer, 22.3% had gynecological malignancies (vulvar (n = 6) or cervical (n = 8) cancer), 11.1% (n = 7) had anal cancer, and 9.5% had other primary tumors. A total of 30.2% (n = 19) underwent PE for a primary tumor and 69.8% (n = 44) for recurrent cancer. The 30-day in-hospital mortality was 0%. Neoadjuvant treatment was administered to 65.1% (n = 41) of the patients and correlated significantly with postoperative complications (odds ratio 4.441; 95% CI: 1.375-14.342, P > 0.05). R0, R1, R2, and Rx resections were achieved in 65.1%, 19%, 1.6%, and 14.3% of the patients, respectively. In patients undergoing R0 resection, 2-year OS and RFS were 73.2% and 52.4%, respectively. Resection status was a significant risk factor for recurrence-free and overall survival (OS) in univariate analysis. Multivariate analysis revealed age (P = 0.021), ASA ≥ 3 (P = 0.005), high blood loss (P = 0.028), low preoperative hemoglobin level (P < 0.001), nodal positivity (P < 0.001), and surgical complications (P = 0.003) as independent risk factors for OS. CONCLUSION: Pelvic exenteration is a procedure with high morbidity rates but remains the only curative option for advanced or recurrent colorectal and non-colorectal cancer in the pelvis.
Assuntos
Neoplasias do Ânus , Exenteração Pélvica , Neoplasias Retais , Humanos , Recidiva Local de Neoplasia/cirurgia , Exenteração Pélvica/efeitos adversos , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation. BACKGROUND DATA: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear. METHODS: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint. RESULTS: Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy [odds ratio 0.27, 95% confidence interval (CI) 0.09-0.88; P = 0.029]. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups. CONCLUSION: A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts. TRIAL REGISTRATION: German Clinical Trials Register DRKS 00004900.
Assuntos
Hemotórax/epidemiologia , Pneumotórax/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Implantação de Prótese/métodos , Dispositivos de Acesso Vascular , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate whether liver metastases contribute to metastatic spread of colorectal cancer (CRC) by shedding intact tumor cells. BACKGROUND: Metastases represent the primary cause of death in CRC. Understanding the metastatic activity of metastases and which patients are at high risk for tumor cell dissemination may, therefore, have significant influence on cancer care in the future. METHODS: Circulating tumor cells (CTCs) were detected in the hepatic inflow (portal venous blood [PVB]) and outflow compartment (hepatic venous blood [HVB]) of a training (nâ=â55) and validation (nâ=â50) set using the CellSearch system. Isolated CTC from the HVB were subjected to gene expression analyses by quantitative polymerase chain reaction. RESULTS: CTC detection rate (37.2% vs 19.6%; Pâ=â0.04) and count (mean: 12.7, SEM:â±â5.9 vs 1.9;â±â1.2; Pâ=â0.01) were significantly higher in HVB compared to PVB. The increased CTC detection rate (54% vs 11.4%; Pâ<â0.001) and CTC count (14.7â±â5.1 vs 1.1â±â0.6; Pâ<â0.001) in the HVB compared to the PVB compartment was confirmed in the validation cohort. Expression of epithelial markers and genes involved in cell-to-cell and cell-to-matrix adhesion was reduced in CTC compared to tumor cells in liver metastases. Metastasis size greater than 5âcm was associated with CTC shedding from established liver metastases in the training and validation cohorts. CONCLUSIONS: Colorectal liver metastases shed intact tumor cells with an invasive phenotype. Metastasis size serves as a surrogate marker for metastatic activity of colorectal liver metastases.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Veias Hepáticas , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células Neoplásicas Circulantes/patologia , Veia Porta , Estudos ProspectivosRESUMO
Complete surgical resection with microscopically tumor-free resection margins (R0) is the most important survival determinant for patients with localized pancreatic cancer. The medial and posterior resection margins are the dominant sites of microscopic tumor involvement, and outline the so-called mesopancreas. In this study, we present a modified surgical approach to the superior mesenteric artery, celiac trunc, and mesopancreas during pancreatoduodenectomy, which enables a comfortable exposure and radical en bloc clearance of the mesopancreas and the tissue adjacent to the superior mesenteric artery. The dissection of the mesopancreas is directed from the ventral aspect of the portal vein downward along the superior mesenteric artery and the celiac trunc, before the transection of the duodenal mesentery is accomplished. The described technique complements the established surgical approaches to pancreatic head tumors, and is indicated in the absence of portal vein infiltration. J. Surg. Oncol. 2016;113:668-671. © 2016 Wiley Periodicals, Inc.
Assuntos
Adenocarcinoma/cirurgia , Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adenocarcinoma/diagnóstico por imagem , Dissecação/métodos , Humanos , Margens de Excisão , Artéria Mesentérica Superior/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Radiografia Intervencionista , Tomografia Computadorizada por Raios XRESUMO
Epithelial-to-mesenchymal transition (EMT) contributes significantly to tumor progression and metastasis. The assessment of EMT-associated transcription factors could be a promising approach to identify biomarkers and potential therapeutic targets in colorectal cancer. In our study, we focused on the transcription factor "Sine oculis homeobox" (SIX) 1, which is a member of the superfamily of the homeobox genes and has been described to promote EMT in different types of tumors. Immunohistochemistry against SIX1 was performed on colorectal mucosa, adenomas, carcinomas-in situ and primary adenocarcinomas. An expression score was developed and subsequently assessed for its prognostic value in two independent cohorts. Cohort 1 consisted of 128 patients with stage I-III colorectal cancer; cohort 2 included 817 patients with stage I-III colorectal cancer who had participated in the DACHS study. HCT-116 cells were transfected with SIX1 plasmids and subjected to migration and colony formation assays. The expression of SIX1 increases gradually from mucosa to colorectal adenocarcinomas (p > 0.0001). Univariate and multivariate analyses reveal that high expression of SIX1 is associated with decreased overall survival (cohort 1: HR: 4.01, CI: 1.20-14.07, p = 0.025; cohort 2: HR: 1.43, CI: 1.014-2.02, p = 0.047). Overexpression of SIX1 induces a more mesenchymal-like phenotype in HCT-116 cells and enhances tumor migration. High expression of SIX1 is an independent prognostic marker in colorectal cancer. It might be a promising biomarker to stratify patients into different risk groups. Moreover, targeting SIX1 might be a novel therapeutic approach in patients with colorectal cancer.
Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Homeodomínio/metabolismo , Adenocarcinoma/patologia , Adenoma/patologia , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Proteínas de Homeodomínio/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , PrognósticoRESUMO
PURPOSE: Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS: Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS: A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group (P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION: Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.
Assuntos
Neoplasias do Colo , Humanos , Feminino , Masculino , Idoso , Neoplasias do Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Metástase Neoplásica , Idoso de 80 Anos ou mais , AdultoRESUMO
Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11â¯700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.
Assuntos
Biguanidas , Laparotomia , Infecção da Ferida Cirúrgica , Irrigação Terapêutica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Masculino , Feminino , Laparotomia/efeitos adversos , Pessoa de Meia-Idade , Biguanidas/uso terapêutico , Biguanidas/administração & dosagem , Idoso , Cuidados Intraoperatórios/métodos , AdultoRESUMO
BACKGROUND: Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer. METHODS: The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy. RESULTS: We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48-0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85-1.00). However, it was associated with increased perioperative mortality (1.48; 1.08-2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23-2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39-0.72), with no impact on perioperative outcome and long-term survival. CONCLUSIONS: Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation.
Assuntos
Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/radioterapia , Humanos , Prognóstico , Radioterapia AdjuvanteRESUMO
BACKGROUND: The detrimental impact of malnutrition and cachexia in cancer patients subjected to surgical resection is well established. However, how systemic and local metabolic alterations in cancer patients impact the serum metabolite signature, thereby leading to cancer-specific differences, is poorly defined. In order to implement metabolomics as a potential tool in clinical diagnostics and disease follow-up, targeted metabolite profiling based on quantitative measurements is essential. We hypothesized that the quantitative metabolic profile assessed by 1 H nuclear magnetic resonance (NMR) spectroscopy can be used to identify cancer-induced catabolism and potentially distinguish between specific tumour entities. Importantly, to prove tumour dependency and assess metabolic normalization, we additionally analysed the metabolome of patients' sera longitudinally post-surgery in order to assess metabolic normalization. METHODS: Forty two metabolites in sera of patients with tumour entities known to cause malnutrition and cachexia, namely, upper gastrointestinal cancer and pancreatic cancer, as well as sera of healthy controls, were quantified by 1 H NMR spectroscopy. RESULTS: Comparing serum metabolites of patients with gastrointestinal cancer with healthy controls and pancreatic cancer patients, we identified at least 15 significantly changed metabolites in each comparison. Principal component and pathway analysis tools showed a catabolic signature in preoperative upper gastrointestinal cancer patients. The most specifically upregulated metabolite group in gastrointestinal cancer patients was ketone bodies (3-hydroxybutyrate, P < 0.0001; acetoacetate, P < 0.0001; acetone, P < 0.0001; false discovery rate [FDR] adjusted). Increased glycerol levels (P < 0.0001), increased concentration of the ketogenic amino acid lysine (P = 0.03) and a significant correlation of 3-hydroxybutyrate levels with branched-chained amino acids (leucine, P = 0.02; isoleucine, P = 0.04 [FDR adjusted]) suggested that ketone body synthesis was driven by lipolysis and amino acid breakdown. Interestingly, the catabolic signature was independent of the body mass index, clinically assessed malnutrition using the nutritional risk screening score, and systemic inflammation assessed by CRP and leukocyte count. Longitudinal measurements and principal component analyses revealed a quick normalization of key metabolic alterations seven days post-surgery, including ketosis. CONCLUSIONS: Together, the quantitative metabolic profile obtained by 1 H NMR spectroscopy identified a tumour-induced catabolic signature specific to upper gastrointestinal cancer patients and enabled monitoring restoration of metabolic homeostasis after surgery. This approach was critical to identify the obtained metabolic profile as an upper gastrointestinal cancer-specific signature independent of malnutrition and inflammation.
Assuntos
Neoplasias Gastrointestinais , Desnutrição , Neoplasias Pancreáticas , Humanos , Ácido 3-Hidroxibutírico , Caquexia/etiologia , Caquexia/metabolismo , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/metabolismo , Inflamação/metabolismo , Leucina , Desnutrição/etiologia , Desnutrição/metabolismo , Neoplasias Pancreáticas/metabolismo , MetabolômicaRESUMO
BACKGROUND: The prognostic role of circulating tumor cells (CTCs) has been established for colorectal cancer (CRC). We investigated the qualitative and quantitative detection of CTC in the central (CVBC) and mesenteric (MVBC) venous blood compartments to elucidate the patterns of hematogenous tumor cell dissemination in patients with CRC. METHODS: A total of 200 patients were enrolled prospectively. Blood samples were collected from the tumor-draining vein and via a central venous line. CTCs were detected and quantified by using the CellSearch system. Factors associated with CTC detection in both compartments were analyzed by using univariate and multivariate analyses. RESULTS: CTC analyses were performed in the CVBC and MVBC in 200 and 80 patients, respectively. CTCs were found at a higher rate (P=0.01) and at a higher count (P=0.006) in the MVBC compared with the CVBC. On multivariate analyses, stage IV disease (odds ratio, 3.83; 95% confidence interval, 1.42-10.35) and increased preoperative carbohydrate antigen 19-9 level (odds ratio, 3.57; 1.30-9.79) were associated with CTC detection in the CVBC. CTCs were detected more frequently (P=0.05) and at higher numbers (P=0.05) in the CVBC of patients with low compared with mid or high rectal tumors. CONCLUSIONS: The qualitative and quantitative detection of CTCs is higher in the MVBC compared with the CVBC of patients with CRC.
Assuntos
Cateterismo Venoso Central , Compartimento Celular , Neoplasias Colorretais/patologia , Mesentério/irrigação sanguínea , Mesentério/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Although blood group 0 is associated with a reduced risk of pancreatic cancer, little is known about the role of AB0 blood group antigens in disease progression. We assessed the prognostic relevance of AB0 blood status in a large cohort of patients with resected pancreatic cancer. METHODS: A total of 627 patients, who underwent resection for pancreatic ductal adenocarcinoma between October 2001 and December 2008 were enrolled. The relationship between AB0 blood group status and outcome was analyzed using univariate and multivariate Cox regression analyses. RESULTS: In patients with pancreatic cancer the incidence of blood group 0 (31%) was lower compared to 13.044 patients without pancreatic cancer (38%) (p = 0.0005). There were no significant differences in clinicopathologic characteristics among patients with different AB0 blood groups. The 3-year and 5-year overall survival rates were 29% and 14%. On univariate analysis AB0 blood group status did not correlate with survival (p = 0.39). Multivariate analysis, however, revealed a favorable and independent impact of blood group 0 on survival (Hazard ratio 0.78; 95% confidence interval 0.62 - 0.99; p = 0.037). CONCLUSION: AB0 blood group status is associated independently with the prognosis of patients with resected pancreatic cancer.
Assuntos
Sistema ABO de Grupos Sanguíneos , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Currently, it remains unclear, if patients with colon cancer and synchronous unresectable metastases who present without severe symptoms should undergo resection of the primary tumour prior to systemic chemotherapy. Resection of the primary tumour may be associated with significant morbidity and delays the beginning of chemotherapy. However, it may prevent local symptoms and may, moreover, prolong survival as has been demonstrated in patients with metastatic renal cell carcinoma. It is the aim of the present randomised controlled trial to evaluate the efficacy of primary tumour resection prior to systemic chemotherapy to prolong survival in patients with newly diagnosed colon cancer who are not amenable to curative therapy. METHODS/DESIGN: The SYNCHRONOUS trial is a multicentre, randomised, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases are eligible for inclusion. Exclusion criteria are primary tumour-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumour as well as systemic chemotherapy is provided according to the standards of the participating institution. The primary endpoint is overall survival that is assessed with a minimum follow-up of 36 months. Furthermore, it is the objective of the trial to assess the safety of both treatment strategies as well as quality of life. DISCUSSION: The SYNCHRONOUS trial is a multicentre, randomised, controlled trial to assess the efficacy and safety of primary tumour resection before beginning of systemic chemotherapy in patients with metastatic colon cancer not amenable to curative therapy. TRIAL REGISTRATION: ISRCTN30964555.
Assuntos
Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Cirurgia Colorretal , Antineoplásicos/uso terapêutico , Carcinoma/mortalidade , Carcinoma/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Cirurgia Colorretal/métodos , Terapia Combinada , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Qualidade de Vida , Análise de SobrevidaRESUMO
BACKGROUND: Digital innovations in medicine are disruptive technologies that can change the way diagnostic procedures and treatments are delivered. Such innovations are typically designed in teams with different disciplinary backgrounds. This paper concentrates on 2 interdisciplinary research teams with 20 members from the medicine and engineering sciences working jointly on digital health solutions. OBJECTIVE: The aim of this paper was to identify factors on the individual, team, and organizational levels that influence the implementation of interdisciplinary research projects elaborating on digital applications for medicine and, based on the results, to draw conclusions for the proactive design of the interdisciplinary research process to make these projects successful. METHODS: To achieve this aim, 2 interdisciplinary research teams were observed, and a small case study (response rate: 15/20, 75%) was conducted using a web-based questionnaire containing both closed and open self-report questions. The Spearman rank correlation coefficient was calculated to analyze the quantitative data. The answers to the open-ended questions were subjected to qualitative content analysis. RESULTS: With regard to the interdisciplinary research projects investigated, the influencing factors of the three levels presented (individual, team, and organization) have proven to be relevant for interdisciplinary research cooperation. CONCLUSIONS: With regard to recommendations for the future design of interdisciplinary cooperation, management aspects are addressed, that is, the installation of a coordinator, systematic definition of goals, required resources, and necessary efforts on the part of the involved interdisciplinary research partners. As only small groups were investigated, further research in this field is necessary to derive more general recommendations for interdisciplinary research teams. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00023909, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023909â; German Clinical Trials Register, DRKS00025077, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00025077.
RESUMO
Background: Cinacalcet is a calcimimetic drug that has increasingly been used as a bridging therapy for primary hyperparathyroidism (pHPT), especially during the COVID-19 pandemic. The aim of our study was to investigate if preoperative cinacalcet therapy affects intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy, which is an important indicator for the success of surgery. Methods: In this single-center retrospective analysis, we studied the outcomes of 72 patients who underwent surgery for pHPT. We evaluated two groups: those with cinacalcet therapy before operationthe cinacalcet group (CG)and those without medical therapy preoperatively (non-CG). In order to perform a between-group comparison of time trends, we fit a linear mixed-effects model with PTH as the response variable and predictors PTH levels preoperatively, group (cinacalcet yes/no), time, the group-by-time interaction, and a random intercept (per subject). Results: Our cohort included 51 (71%) women and 21 (29%) men, who were operated upon for pHPT in the period from January 2018 until August 2021. All patients were diagnosed with pHPT and 54% of the cohort were symptomatic for hypercalcemia. Moreover, 30% of the patients were treated with cinacalcet as a bridging therapy preoperatively, and this increased during the COVID-19 pandemic, as 64% of this group were treated in the last two years. Calcium values were significantly different before (p < 0.001) and after (p = 0.0089) surgery, but calcium level change did not differ significantly between the CG and non-CG. Parathyroid hormone (PTH) levels dropped significantly in both groups during 10 min IOPTH monitoring (p < 0.001), but there was no significant difference between the two groups (p = 0.212). Conclusions: In the examined patient cohort, the use of cinacalcet did not affect the value of IOPTH monitoring during surgery for pHPT.
RESUMO
INTRODUCTION: It has been shown that cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for patients suffering from peritoneal malignancies. Despite good results, there is an ongoing debate about this treatment due to perioperative morbidity. The aim of this study is to identify relevant risk factors for an unfavorable postoperative outcome after CRS and HIPEC. MATERIALS AND METHODS: A retrospective analysis of a prospectively recorded database of all patients undergoing CRS and HIPEC between 2013 and 2020 in the Department of Surgery of the University Hospital Dresden was performed with a special focus on certain surgical steps of multivisceral resection, one- or 2- stage CRS/HIPEC and underlying diagnosis as possible risk factors for worse postoperative course. RESULTS: N = 173 CRS and HIPEC procedures were performed for various diagnoses. Relevant postoperative morbidity was 24% and 30d-mortality 1.2%. Simultaneous liver resections, preoperative hypalbuminemia and 2-staged CRS/HIPEC were significant risk factors for a worse postoperative course in multivariable analysis. Assessment of the association of simultaneous anastomoses and morbidity and mortality was inconclusive. CONCLUSION: CRS and HIPEC is a safe treatment without relevant intraoperative morbidity and mortality and acceptable postoperative outcome. One-stage CRS/HIPEC should be preferred.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Humanos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Estudos Retrospectivos , Hipertermia Induzida/efeitos adversos , Terapia Combinada , Morbidade , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The skills, knowledge and resources to search for, find, understand, evaluate and apply health information is defined as health literacy (HL). If individuals want to use health information from the Internet, they need Digital Health Literacy (eHL), which in addition to HL also includes, for example, media literacy. If information cannot be found or understood by patients due to low (e)HL, patients will not have the opportunity to make informed decisions. In addition, many health apps for self-management or prevention also require (e)HL. Thus, it follows that active participation in healthcare, in terms of Person-Centered Care (PCC) is only possible through (e)HL. Currently, there is a great need to strengthen these competencies in society to achieve increased empowerment of patients and their health. However, at the same time, there is a need to train and improve competencies in the field of healthcare professionals so that they can counsel and guide patients. This article provides an overview with a focus on HL and eHL in healthcare, shows the opportunities to adapt services and describes the possible handling of patients with low (e)HL. In addition, the opportunities for patients and healthcare professionals to improve (e)HL are highlighted.