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1.
HPB (Oxford) ; 24(8): 1362-1364, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35289281

RESUMO

BACKGROUND: The first-line therapy for liver malignancies is a radical extended liver resection. This high-risk operation has a high incidence of post-hepatectomy liver failure (PHLF) due to a small future liver remnant (FLR). One of the procedures to increase the FLR is the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) which is still associated with high morbidity and mortality. Here, we present a new, less invasive ALPPS variant that may be associated with lower morbidity. METHODS: SoftALPPS is characterized by reduced trauma to the liver tissue and individual adaptation to the patient's health constitution. In softALPPS, portal vein embolization (PVE) is performed instead of portal vein ligation (PVL) after complete recovery of liver function. In addition, a non-absorbable foil was avoided in order to be able to extend the interval to step two or skip step two when required. RESULTS: Four patients successfully underwent softALPPS. Two of these patients have been followed-up for over a year (one patient with Klatskin tumor, one patient with extensive HCC). Both patients show no evidence of recurrence after 12 months and are in good medical condition. The other two patients who recently had surgery are also doing well. CONCLUSION: SoftALPPS offers the chance to curatively resect patients with high tumor burden of the liver even when the FLR is inadequate. This individual therapy method can give patients the possibility of complete tumor resection and can help to reduce perioperative morbidity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Ligadura/métodos , Fígado/patologia , Veia Porta/patologia , Veia Porta/cirurgia , Resultado do Tratamento
2.
Cancers (Basel) ; 14(2)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35053610

RESUMO

Growing evidence has indicated that pyroptosis functions in the development of cancer. Nonetheless, specific roles of pyroptosis-related genes in tumor progression, immune response, prognosis, and immunotherapy have not been thoroughly elucidated. After a comprehensive evaluation of pyroptosis genes, unsupervised clustering was performed to generate three distinct clusters from hepatocellular carcinoma (HCC) samples. Three distinct pyroptosis-related molecular subtypes comprising three gene clusters that had differential prognostic effects on patient survival were then identified. Immune characteristics analyses revealed diversified immune cell infiltration among the subtypes. Two clusters served as immune-hot phenotypes associated with significantly poorer survival compared to a remaining third immune-cold cluster. Among these, the immune-hot clusters were characterized by abundant adaptive immune cell infiltration, active CD4+ and CD8+ T cells, high total leukocyte counts and tumor growth status, and lower Th17 cell and M2 macrophage densities. Then, risk scores indicated that low-risk patients were more sensitive to anti-tumor therapy. Subsequently, we found a significant correlation between pyroptosis and prognosis in HCC and that pyroptosis genes drive the heterogeneity of the tumor microenvironment. The risk scoring system, based on pyroptosis-related differentially expressed genes, was established to evaluate the individual outcomes and contribute to new insights into the molecular characterization of pyroptosis-related subtypes.

3.
BMC Surg ; 21(1): 411, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863157

RESUMO

BACKGROUND: The ongoing SARS-COV-2 pandemic has severe implications for people and healthcare systems everywhere. In Germany, worry about the consequences of the pandemic led to the deferral of non-emergency surgeries. Tumor surgery accounts for a large volume in the field of visceral surgery and cannot be considered purely elective. It is not known how the SARS-COV-2 pandemic has changed the surgical volume in tumor patients. METHODS: Retrospective analysis of the amount of oncological surgeries in three academic visceral surgery departments in Bavaria, Germany, in 2020. Procedures were split into subgroups: Upper Gastrointestinal (Upper GI), Colorectal, Hepato-Pancreato-Biliary (HPB), Peritoneal and Endocrine. Procedures in 2020 were compared to a reference period from January 1st, 2017 to December 31st 2019. Surgical volume was graphically merged with SARS-COV-2 incidence and the number of occupied ICU beds. RESULTS: Surgical volume decreased by 7.6% from an average of 924 oncologic surgeries from 2017 to 2019 to 854 in 2020. The decline was temporally associated with the incidence of infections and ICU capacity. Surgical volume did not uniformly increase to pre-pandemic levels in the months following the first pandemic wave with lower SARS-COV-2 incidence and varied according to local incidence levels. The decline was most pronounced in colorectal surgery where procedures declined on average by 26% following the beginning of the pandemic situation. CONCLUSION: The comparison with pre-pandemic years showed a decline in oncologic surgeries in 2020, which could have an impact on lost life years in non-COVID-19 patients. This decline was very different in subgroups which could not be solely explained by the pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Alemanha/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos
4.
Dtsch Arztebl Int ; 118(33-34): 565, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34725034
5.
Dtsch Arztebl Int ; 118(14): 244-249, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-34114553

RESUMO

BACKGROUND: Appendectomy is the gold standard for treatment of acute appendicitis. However, recent studies favor primary antibiotic therapy. The aim of this observational study was to explore changes in the numbers of operations for acute appendicitis in the period 2010-2017, paying special attention to disease severity. METHODS: Data from diagnosis-related group statistics were used to analyze the trends, mortality, and complication rates in the surgical treatment of appendicitis in Germany between 2010 and 2017. All cases of appendectomy after a diagnosis of appendicitis were included. RESULTS: Altogether, 865 688 inpatient cases were analyzed. The number of appendectomies went down by 9,8%, from 113 614 in 2010 to 102 464 in 2017, while the incidence fell from 139/100 000 in 2010 to 123/100 000 in 2017 (standardized by age group). This decrease is due to the lower number of operations for uncomplicated appendicitis (79 906 in 2017 versus 93 135 in 2010). Hospital mortality decreased both in patients who underwent surgical treatment of complicated appendicitis (0.62% in 2010 versus 0.42% in 2017) and in those with a complicated clinical course (5.4% in 2010 versus 3.4% in 2017). CONCLUSION: Decisions on the treatment of acute appendicitis in German hospitals follow the current trend towards non-surgical management in selected patients. At the same time, the care of acute appendicitis has improved with regard to overall hospital morbidity and hospital mortality.


Assuntos
Apendicite , Laparoscopia , Doença Aguda , Antibacterianos/uso terapêutico , Apendicectomia , Apendicite/epidemiologia , Apendicite/cirurgia , Alemanha/epidemiologia , Humanos , Tempo de Internação , Estudos Retrospectivos , Resultado do Tratamento
6.
Dig Surg ; 38(4): 259-265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34058733

RESUMO

BACKGROUND: The first COVID-19 pandemic wave hit most of the health-care systems worldwide. The present survey aimed to provide a European overview on the COVID-19 impact on surgical oncology. METHODS: This anonymous online survey was accessible from April 24 to May 11, 2020, for surgeons (n = 298) who were contacted by the surgical society European Digestive Surgery. The survey was completed by 88 surgeons (29.2%) from 69 different departments. The responses per department were evaluated. RESULTS: Of the departments, 88.4% (n = 61/69) reported a lower volume of patients in the outpatient clinic; 69.1% (n = 47/68) and 75.0% (n = 51/68) reported a reduction in hospital bed and the operating room capacity, respectively. As a result, the participants reported an average reduction of 29.3% for all types of oncological resections surveyed in this questionnaire. The strongest reduction was observed for oncological resections of hepato-pancreatico-biliary (HPB) cancers. Of the interviewed surgeons, 68.7% (n = 46/67) agreed that survival outcomes will be negatively impacted by the pandemic. CONCLUSION: The first COVID-19 pandemic wave had a significant impact on surgical oncology in Europe. The surveyed surgeons expect an increase in the number of unresectable cancers as well as poorer survival outcomes due to cancellations of follow-ups and postponements of surgeries.


Assuntos
COVID-19/epidemiologia , Número de Leitos em Hospital/estatística & dados numéricos , Neoplasias/cirurgia , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Oncologia Cirúrgica/estatística & dados numéricos , Adulto , Assistência Ambulatorial/estatística & dados numéricos , COVID-19/diagnóstico , Quimioterapia Adjuvante/estatística & dados numéricos , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Salas Cirúrgicas/estatística & dados numéricos , Inquéritos e Questionários , Taxa de Sobrevida , Tempo para o Tratamento/estatística & dados numéricos
7.
Chirurg ; 92(6): 559-566, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-34009441

RESUMO

BACKGROUND: During the first wave of the COVID-19 pandemic, the downregulation of all elective interventions during the period from 15 March 2020 to 15 May 2020 in Germany led to a decrease in operations. The impact on the number of specific operations in visceral surgery is so far unknown. METHODS: This retrospective study included 301 patients who underwent a cholecystectomy or appendectomy at a university hospital or a primary care facility between 15 March 2020 and 15 May 2020 (vs. 2018 and 2019). The number of cases and the clinical outcomes were analyzed. RESULTS: The suspension of elective surgery resulted in a significant reduction in elective cholecystectomy and emergency appendectomy. At the University Hospital the number of appendectomies decreased by 33% from 24 in 2018 to 16 in 2020 and the number of cholecystectomies declined by 57% from 30 in 2018 to 13 in 2020. At the primary care hospital, the number of appendectomy patients decreased by 48% from 23 in 2018 to 12 in 2020 and the number of cholecystectomies increased from the year 2018 to 2019 and subsequently declined by 30% in 2020. The duration of surgery, length of hospital stay and clinical course of patients did not significantly differ from the previous year time periods. CONCLUSIONS: During the first wave of the COVID-19 pandemic, the lockdown resulted in a significant reduction in frequently carried out visceral surgical interventions. In order to maintain the optimal medical care for the total population, current options for surgical and conservative treatment must be weighed against each other depending on the numbers of local infections and the individual comorbidities of the patients.


Assuntos
COVID-19 , Pandemias , Apendicectomia , Controle de Doenças Transmissíveis , Alemanha , Humanos , Atenção Primária à Saúde , Estudos Retrospectivos , SARS-CoV-2
8.
Int J Colorectal Dis ; 36(7): 1487-1498, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33855608

RESUMO

PURPOSE: Little is known about difference between synchronous colorectal cancer (SCRC) and metachronous colorectal cancer (MCRC) despite the relevance for this selected patient group. The aim of this retrospective review was to analyze patients with SCRC and MCRC. METHODS: All patients who underwent surgery for SCRC and MCRC between 1982 and 2019 were included in this retrospective analysis of our tertiary referral center. Clinical, histological, and molecular genetic characteristics were analyzed. The primary endpoint was cause-specific survival, evaluated by the Kaplan-Meier method. Secondary endpoints were recurrence-free survival and the identification of prognostic factors. RESULTS: Overall, 3714 patients were included in this analysis. Of those, 3506 (94.4%) had a primary unifocal colorectal cancer (PCRC), 103 (2.7%) had SCRC, and 105 (2.8%) had MCRC. SCRC occurred more frequently in elderly (p=0.009) and in male patients (p=0.027). There were no differences concerning tumor stages or grading. Patients with SCRC did not show altered recurrence or survival rates, as compared to unifocal tumors. However, MCRC had a lower rate of recurrence, compared to PCRC (24% vs. 41%, p=0.002) and a lower rate of cause-specific death (13% vs. 37%, p<0.001). Five-year cause-specific survival rates were 63±1% for PCRC, 62±6% for SCRC (p=0.588), and 88±4% for MCRC (p<0.001). Multivariable analysis revealed that MCRC were an independent favorable prognostic parameter regarding case-specific survival. CONCLUSION: Patients with SCRC seem to not have a worse prognosis compared to patients with PCRC. Noteworthy, patients with MCRC showed better survival rates in this retrospective analysis.


Assuntos
Neoplasias Colorretais , Neoplasias Primárias Múltiplas , Idoso , Neoplasias Colorretais/genética , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas/cirurgia , Prognóstico , Estudos Retrospectivos
9.
Int J Colorectal Dis ; 36(11): 2419-2426, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33876296

RESUMO

PURPOSE: Despite primary conservative therapy for Crohn's disease, a considerable proportion of patients ultimately needs to undergo surgery. Presumably, due to the increased use of biologics, the number of surgeries might have decreased. This study aimed to delineate current case numbers and trends in surgery in the era of biological therapy for Crohn's disease. METHODS: Nationwide standardized hospital discharge data (diagnosis-related groups statistics) from 2010 to 2017 were used. All patients who were admitted as inpatient Crohn's disease cases in Germany were included. Time-related development of admission numbers, rate of surgery, morbidity, and mortality of inpatient Crohn's disease cases were analyzed. RESULTS: A total number of 201,165 Crohn's disease cases were included. Within the analyzed time period, the total number of hospital admissions increased by 10.6% (n = 23,301 vs. 26,069). While gender and age distribution remained comparable, patients with comorbidities such as stenosis formation (2010: 10.1%, 2017: 13.4%) or malnutrition (2010: 0.8%, 2017: 3.2%) were increasingly admitted. The total number of all analyzed operations for Crohn's disease increased by 7.5% (2010: n = 1567; 2017: n = 1694). On average, 6.8 ± 0.2% of all inpatient patients received ileocolonic resections. Procedures have increasingly been performed minimally invasive (2010: n = 353; 2017: n = 687). The number of postoperative complications remained low. CONCLUSION: Despite the development of novel immunotherapeutics, the number of patients requiring surgery for Crohn's disease remains stable. Interestingly, patients have been increasingly hospitalized with stenosis and malnutrition. The trend towards more minimally invasive operations has not relevantly changed the rate of overall complications.


Assuntos
Doença de Crohn , Terapia Biológica , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Grupos Diagnósticos Relacionados , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias
10.
Dig Surg ; 38(2): 158-165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33640885

RESUMO

BACKGROUND: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. METHODS: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. RESULTS: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. DISCUSSION/CONCLUSIONS: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.


Assuntos
COVID-19/prevenção & controle , Acessibilidade aos Serviços de Saúde/tendências , Pancreatectomia/tendências , Neoplasias Pancreáticas/cirurgia , Padrões de Prática Médica/tendências , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Assistência ao Convalescente/tendências , Atitude do Pessoal de Saúde , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , Pesquisas sobre Atenção à Saúde , Acessibilidade aos Serviços de Saúde/normas , Humanos , Controle de Infecções/métodos , Controle de Infecções/tendências , Estadiamento de Neoplasias , Pancreatectomia/normas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Assistência Perioperatória/tendências , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Tempo para o Tratamento/normas , Tempo para o Tratamento/tendências
11.
BMC Surg ; 20(1): 313, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272227

RESUMO

BACKGROUND: During the first wave of the COVID-19 pandemic, German health care centres were restructured for the treatment of COVID-19 patients. This was accompanied by the suspension of the surgical programme. The aim of the survey was to determine the effects of COVID-19 on surgical care in non-university hospitals in Germany. METHODS: This cross-sectional study was based on an anonymous online survey, which was accessible from April 24th to May 10th, 2020 for surgeons of the Konvent der leitenden Krankenhauschirurgen (Convention of leading Hospital Surgeons) in Germany. The analysis comprised of 22.8% (n = 148/649) completed surveys. RESULTS: Communication and cooperation with authorities, hospital administration and other departments were largely considered sufficient. In the early phase of the COVID-19 pandemic, 28.4% (n = 42/148) of the respondents complained about a short supply of protective equipment available for the hospital staff. 7.4% (n = 11/148) of the participants stated that emergency operations had to be postponed or rescheduled. A decreased quantity of emergency surgical procedures and a decreased number of surgical emergency patients treated in the emergency room was reported in 43.9% (n = 65/148) and 63.5% (n = 94/148), respectively. Consultation and treatment of oncological patients in the outpatient clinic was decreased in 54.1% (n = 80/148) of the surveyed hospitals. To increase the capacity for COVID-19 patients, a reduction of bed and operating room occupancy of 50.8 ± 19.3% and 54.2 ± 19.1% were reported, respectively. Therefore, 90.5% (n = 134/148) of all participants expected a loss of revenue of 28.2 ± 12.9% in 2020. CONCLUSION: The first wave of the COVID-19 pandemic had a significant impact on surgical care in Germany. The reduction in the bed and the operating room capacity may have lead to considerable delays in urgent and semi-elective surgical interventions. In addition to the risk of worsening patient care, we anticipate severe financial damage to the clinics in 2020 and beyond. National and supranational planning is urgently needed to ensure the surgical care of patients during the ongoing COVID-19 pandemic.


Assuntos
COVID-19 , Centro Cirúrgico Hospitalar/organização & administração , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Estudos Transversais , Alemanha , Número de Leitos em Hospital , Hospitais , Humanos , Pandemias
12.
Chirurg ; 91(9): 762-768, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32776251

RESUMO

BACKGROUND AND AIMS: From the beginning of the SARS-CoV­2 pandemic the German healthcare system focused on the treatment of COVID-19 patients. This was accompanied by the suspension of all elective operations. The aim of this study was to investigate the impact of the SARS-CoV­2 pandemic on general and visceral surgery in university hospitals in Germany. METHODS: This cross-sectional study was based on an anonymous survey, which was accessible online from 3 April 2020 to 17 April 2020 for the surgical departments of university hospitals in Germany. In total 73% (n = 29/40) of the hospitals participated in the survey. RESULTS: Cooperation with the authorities and the hospital administration was generally considered adequate; however, only 3% (1/29) and 7% (2/29) fully agreed with the statement that the health authorities at the federal and state level, respectively, were supportive of general and visceral surgery. The hospital directors expect an average loss of revenues of 28 ± 16%. There was an average reduction in beds or operating room capacity of 38% and 45%, respectively. In addition, 11% of the medical personnel in general and visceral surgery were reallocated to other departments. CONCLUSION: The SARS-CoV­2 pandemic has a significant impact on academic general and visceral surgery in Germany. The reduction in beds and operating room capacity can lead to considerable delays in urgent surgical interventions and financial burdens in 2020 and subsequent years.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Estudos Transversais , Alemanha , Humanos , SARS-CoV-2
13.
FASEB J ; 34(8): 10387-10397, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32539223

RESUMO

TLR3 is implicated in anti-viral immune responses, but may also act as a sensor of tissue damage in the absence of infection. Here, we provide evidence for an essential role of TLR3 in liver regeneration after an acute loss of tissue due to partial hepatectomy. Mice lacking TLR3 had a severe and sustained defect in the restoration of liver tissue with reduced liver-to-body weight ratios even after an extended recovery period of 2 weeks. Hepatocyte cell cycle progression into S phase was impaired in TLR3-deficient mice. Mechanistic analyses revealed that TLR3-deficient mice had markedly reduced systemic levels of active HGF, but had increased amounts of inactive tissue-bound HGF. Importantly, expression of uPA, which orchestrates the processing and release of HGF from the hepatic extracellular matrix, was reduced in regenerating livers of TLR3-deficient mice. In addition, expression of the HGF maturation factor HGFAC was transiently diminished in TLR3-deficient mice. In vitro, engagement of TLR3 directly stimulated expression of uPA by hepatic stellate cells. Thus, TLR3 supports liver regeneration through upregulation of uPA, which promotes the release of preformed HGF from extracellular matrix stores.


Assuntos
Proliferação de Células/fisiologia , Fator de Crescimento de Hepatócito/metabolismo , Hepatócitos/metabolismo , Receptor 3 Toll-Like/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Animais , Matriz Extracelular/metabolismo , Matriz Extracelular/fisiologia , Hepatectomia/métodos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/fisiologia , Fígado/metabolismo , Regeneração Hepática/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Organogênese/fisiologia
14.
FASEB J ; 34(6): 8125-8138, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32329113

RESUMO

The effectiveness of liver regeneration limits surgical therapies of hepatic disorders and determines patient outcome. Here, we investigated the role of the neuropeptide calcitonin gene-related peptide (CGRP) for liver regeneration after acute or chronic injury. Mice deficient for the CGRP receptor component receptor activity-modifying protein 1 (RAMP1) were subjected to a 70% partial hepatectomy or repeated intraperitoneal injections of carbon tetrachloride. RAMP1 deficiency severely impaired recovery of organ mass and hepatocyte proliferation after both acute and chronic liver injury. Mechanistically, protein expression of the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) was decreased in regenerating livers of RAMP1-deficient mice. Lack of RAMP1 was associated with hyperphosphorylation of YAP on Ser127 and Ser397, which regulates YAP functional activity and protein levels. Consequently, expression of various YAP-controlled cell cycle regulators and hepatocyte proliferation were severely reduced in the absence of RAMP1. In vitro, CGRP treatment caused increased YAP protein expression and a concomitant decline of YAP phosphorylation in liver tissue slice cultures of mouse and human origin and in primary human hepatocytes. Thus, our results indicate that sensory nerves represent a crucial control element of liver regeneration after acute and chronic injury acting through the CGRP-RAMP1 pathway, which stimulates YAP/TAZ expression and activity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Regeneração Hepática/fisiologia , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Hepatectomia/métodos , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/fisiologia , Transdução de Sinais/fisiologia , Proteínas de Sinalização YAP
15.
Sci Rep ; 8(1): 12271, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115978

RESUMO

Stimulation of cytosolic nucleic acid sensors of innate immunity by pathogen-derived nucleic acids is important for antimicrobial defence, but stimulation through self-derived nucleic acids may contribute to autoinflammation and cancer. DNA sensing in the cytosol requires the stimulator of interferon genes (STING), while cytosolic RNA sensors use mitochondrial antiviral-signalling protein (MAVS). In a murine model of two-thirds hepatectomy, combined deficiency of MAVS and STING resulted in strongly impaired hepatocyte proliferation and delayed recovery of liver mass. Whereas lack of MAVS and STING did not influence upregulation of the G1-phase cyclins D1 and E1, it substantially reduced the hyperphosphorylation of retinoblastoma protein, attenuated the activation of cyclin-dependent kinase (CDK)-2, delayed upregulation of CDK1 and cyclins A2 and B1, and impaired S-phase entry of hepatocytes. Mechanistically, lack of cytosolic nucleic acid sensors strongly upregulated the anti-proliferative mediators TGF-ß2 and activin A, which was associated with an increased expression of the cell cycle inhibitors p15 and p21. Partial hepatectomy was followed by the release of exosomes with abundant nucleic acid cargo, which may provide ligands for the MAVS and STING pathways. Together, these findings identify a previously unrecognised function of cytosolic nucleic acid sensors of innate immunity for promoting liver regeneration.


Assuntos
Citosol/metabolismo , DNA/metabolismo , Hepatectomia , Imunidade Inata , Regeneração Hepática/imunologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Animais , Ciclo Celular , Proliferação de Células , Hepatócitos/citologia , Hepatócitos/metabolismo , Interleucina-6/biossíntese , Proteínas de Membrana/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Regulação para Cima
16.
Gastrointest Tumors ; 4(1-2): 11-19, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29071260

RESUMO

BACKGROUND: Adjuvant chemotherapy has become the standard form of treatment for all patients with stage III colorectal cancer and is also recommended for patients with stage II disease and defined risk factors. However, clinical studies that evaluate the effect of adjuvant treatment regimens have a selection bias in favor of younger patients, so that even retrospective subgroup analyses cannot define the best therapeutic procedure in elderly patients with comorbidities. SUMMARY: As long as the role of adjuvant chemotherapy in elderly colorectal cancer patients is not investigated in comprehensive trials, no clear recommendations are possible. KEY MESSAGE: An exploratory review of the relevant literature revealed that a formal meta-analysis concerning adjuvant chemotherapy in elderly patients with colorectal cancer is not feasible due to varying definitions of elderly patients, inclusion and exclusion criteria, and a plethora of chemotherapeutic regimens. PRACTICAL IMPLICATIONS: Given the high incidence of colorectal cancer and the median age of 68 years for patients at the time of diagnosis, health economic considerations should promote randomized controlled trials regarding the role of adjuvant chemotherapy in the elderly.

17.
Dtsch Arztebl Int ; 113(29-30): 489-96, 2016 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-27545699

RESUMO

BACKGROUND: If conservative treatment of chronic pancreatitis is unsuccessful, surgery is an option. The choice of the most suitable surgical method can be difficult, as the indications, advantages, and disadvantages of the available methods have not yet been fully documented with scientific evidence. METHODS: In April 2015, we carried out a temporally unlimited systematic search for publications on surgery for chronic pancreatitis. The target parameters were morbidity, mortality, pain, endocrine and exocrine insuffi - ciency, weight gain, quality of life, length of hospital stay, and duration of urgery. Differences between surgical methods were studied with network meta-analysis, and duodenum-preserving operations were compared with partial duodenopancreatectomy with standard meta-analysis. RESULTS: Among the 326 articles initially identified, 8 randomized controlled trials on a total of 423 patients were included in the meta-analysis. The trials were markedly heterogeneous in some respects. There was no significant difference among surgical methods with respect to perioperative morbidity, pain, endocrine and exocrine insufficiency, or quality of life. Duodenumpreserving procedures, compared to duodenopancreatectomy, were associated with a long-term weight gain that was 3 kg higher (p <0.001; three trials), a mean length of hospital stay that was 3 days shorter (p = 0.009; six trials), and a duration of surgery that was 2 hours shorter (p <0.001; five trials). CONCLUSION: Duodenum-preserving surgery for chronic pancreatitis is superior to partial duodenopancreatectomy in multiple respects. Only limited recommendations can be given, however, on the basis of present data. The question of the best surgical method for the individual patient, in view of the clinical manifestations, anatomy, and diagnostic criteria, remains open.


Assuntos
Insuficiência Pancreática Exócrina/mortalidade , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Pancreatectomia/mortalidade , Pancreatite Crônica/mortalidade , Pancreatite Crônica/cirurgia , Complicações Pós-Operatórias/mortalidade , Adulto , Comorbidade , Medicina Baseada em Evidências , Insuficiência Pancreática Exócrina/prevenção & controle , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/estatística & dados numéricos , Pancreatite Crônica/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
18.
Ann Surg Oncol ; 22 Suppl 3: S1212-20, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26350368

RESUMO

BACKGROUND: FOLFIRINOX is an active but relatively toxic chemotherapeutic regimen for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The increased frequency of responding tumors shift interest to neoadjuvant approaches. We report our institutional experience with FOLFIRINOX for therapy-naïve patients with locally advanced and initially unresectable PDAC. METHODS: All patients with unresectable locally advanced PDAC who underwent treatment with FOLFIRINOX at a single center between 2011 and 2014 were identified and evaluated retrospectively regarding chemotherapy response, toxicity, conversion to resectability, and survival. Resectability, response to chemotherapy, and postoperative complications were reported according to NCCN-guidelines, RECIST-criteria, and Clavien-Dindo-classification, respectively. RESULTS: Overall, 14 patients received FOLFIRINOX as first-line therapy for locally advanced and unresectable PDAC. Fifty-seven percent of the patients had severe tumor-related comorbidities at the time of diagnosis, and in 86 %, dose reduction due to toxicity was necessary during a median of seven cycles. Nevertheless, only one patient had progressive disease during FOLFIRINOX, whereas the others experienced stable disease (n = 6) or partial remission (n = 6; no restaging in one patient). Oncological tumor resection was possible in 4 patients (29 % of all patients) with no postoperative mortality and only one grade 2 surgical complication. After a median follow-up of 10 months, 4 of the 14 patients were still in remission, 5 were alive with stable disease under ongoing systemic chemotherapy, and 5 died tumor-related. CONCLUSIONS: FOLFIRINOX is a powerful first-line regimen that leads to resectability in a substantial portion of patients with initially unresectable pancreatic cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
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