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BACKGROUND: Lipoprotein(a) (Lp(a)) is an inherited risk factor for atherosclerotic cardiovascular disease (ASCVD). Limited data exist on Lp(a) values in children. We aimed to evaluate whether Lp(a) concentrations in youth are influenced by BMI. METHODS: 756 blood samples of 248 children with obesity and 264 matched healthy children aged 5 and 18 years, enrolled in the population-based LIFE Child (German civilization diseases cohort) study, were analyzed. Repeat measurements were available in 154 children (1-4 follow ups, ~1 year apart). RESULTS: The median Lp(a) concentration in the total cohort (n = 512) at first visit was 9.7 mg/dL (IQR 4.0-28.3). Lp(a) concentrations between 30-50 mg/dL were observed in 11.5%, while 12.5% exhibited Lp(a) â§50 mg/dL. There was no association of Lp(a) with body mass index (BMI) (ß = 0.004, P = 0.49). Lp(a) levels did not correlate with age or sex, while Lp(a) was associated positively with low-density lipoprotein cholesterol (ß = 0.05, P < 0.0001). The Lp(a) risk category remained stable in 94% of all children in repeated measurements. CONCLUSIONS: The data showed no association of Lp(a) levels in children with BMI, age or sex. Measurement of Lp(a) in youth may be useful to identify children at increased lifetime risk for ASCVD. IMPACT: In youth, Lp(a) levels are not affected by age, sex and BMI. Lp(a) risk categories remain stable over time in repeated measurements in children. Measurement of Lp(a) in children may be useful as an additional factor to identify children at increased lifetime risk for ASCVD and for reverse family screening.
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Índice de Massa Corporal , Lipoproteína(a) , Humanos , Criança , Lipoproteína(a)/sangue , Feminino , Masculino , Adolescente , Pré-Escolar , Fatores Etários , Fatores Sexuais , Fatores de Risco , Estudos de Casos e Controles , LDL-Colesterol/sangue , AlemanhaRESUMO
OBJECTIVE: Peripheral arterial disease (PAD) has been associated with suboptimal treatment, high mortality, and high amputation rates. It is unclear how the COVID-19 (coronavirus disease 2019) pandemic affected this development in a long term context. METHODS: This is a registry based, retrospective, nationwide cohort study including patients hospitalised with PAD as a main or secondary diagnosis and amputation surgery between 2012 - 2021 in Germany. Primary endpoints were population wide major and minor amputation rates, in hospital death, and in hospital mortality rates. Secondary endpoints were same admission revascularisations and in hospital death in the event of complications, i.e., failure to rescue (FTR). Pre-pandemic and pandemic trends, focusing on lockdown periods, were analysed. RESULTS: A total of 365 926 patient records with PAD and amputation surgery were analysed. The median patient age was 75 years and 28.8% were female. Overall population wide amputation and in hospital mortality rates (monthly decrease -0.002/100 000, p < .001, and -0.001/100 000, p< .001, respectively) and in hospital mortality rate (8.0% for 2012 - 2014 vs. 6.5% for 2020 - 2021; p < .001) declined between 2012 and 2020. Concurrently, same admission revascularisations increased (41.0% for 2012 - 2014 vs. 47.0% for 2020 - 2021; p < .001), while FTR decreased in a subset of complications (acute ischaemia, major bleeding, compartment syndrome, and mesenterial ischaemia). In the first pandemic lockdown, there was a temporary trend change to higher major amputations rates (+0.02/100 000; p < .001) and higher in hospital mortality rates (+0.007/100 000; p < .001), which changed to a decrease as of the second lockdown (-0.03/100 000, p = .034, and -0.010/100 000, p < .001, respectively) in an interrupted time series analysis. There was no statistically significant change in observed amputation rates during lockdowns, while observed in hospital mortality rates decreased by 12.0% in the first lockdown (0.22/100 000 vs. 0.25/100 000; p = .005) compared with reference periods of the two previous years. CONCLUSION: Between 2012 and 2021, pre-pandemic trends toward decreasing population wide overall amputation rates, fewer major amputations, more amputation related revascularisation procedures, and lower in hospital mortality were maintained despite a temporary trend to increased major amputations and in hospital mortality during the first COVID-19 related lockdown in Germany.
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PURPOSE: A correlation between the hospital volume and outcome is described for multiple entities of oncological surgery. To date, this has not been analyzed for the surgical treatment of sigmoid diverticulitis. The aim of this study was to explore the impact of the annual caseload per hospital of colon resection on the postoperative incidence of complications, failure to rescue, and mortality in patients with diverticulitis. METHODS: Patients receiving colorectal resection independent from the diagnosis from 2012 to 2017 were selected from a German nationwide administrative dataset. The hospitals were grouped into five equal caseload quintiles (Q1-Q5 in ascending caseload order). The outcome analysis was focused on patients receiving surgery for sigmoid diverticulitis. RESULTS: In total, 662,706 left-sided colon resections were recorded between 2012 and 2017. Of these, 156,462 resections were performed due to sigmoid diverticulitis and were included in the analysis. The overall in-house mortality rate was 3.5%, ranging from 3.8% in Q1 (mean of 9.5 procedures per year) to 3.1% in Q5 (mean 62.8 procedures per year; p < 0.001). Q5 hospitals revealed a risk-adjusted odds ratio of 0.85 (95% CI 0.78-0.94; p < 0.001) for in-hospital mortality compared to Q1 during multivariable logistic regression analysis. High-volume centers showed overall lower complication rates, whereas the failure-to-rescue did not differ significantly. CONCLUSION: Surgical treatment of sigmoid diverticulitis in high-volume colorectal centers shows lower postoperative mortality rates and fewer postoperative complications.
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Colectomia , Colo Sigmoide , Diverticulite , Mortalidade Hospitalar , Humanos , Colectomia/efeitos adversos , Colectomia/estatística & dados numéricos , Colo Sigmoide/cirurgia , Diverticulite/cirurgia , Incidência , Complicações Pós-Operatórias/epidemiologiaRESUMO
PURPOSE: Coronavirus disease 2019 (COVID-19) impacted health care systems around the world. Despite a decrease in emergency admissions, an increased number of complicated forms of diverticulitis was reported. It was the aim of this study to analyze the pandemic impact on diverticulitis management in Germany. METHODS: This is a retrospective population-wide analysis of hospital billing data (2012-2021) of diverticulitis in Germany. Patients were identified based on diagnosis (ICD10) and procedural codes to stratify by conservative and operative management. Primary outcome of interest was admission rates, secondary outcomes were rates of surgical vs conservative treatment and fraction of complicated clinical courses during the pandemic. RESULTS: Of a total of 991,579 cases, 66,424 (6.7%) were admitted during pandemic lockdowns. Conservative treatment was the most common overall (66.9%) and higher during lockdowns (70.7%). Overall admissions and population adjusted rates of surgically treated patients decreased, the latter by 12.7% and 11.3%, corrected to estimated rates, in the two lockdowns. Surgery after emergency presentation decreased by 7.1% (p=0.053) and 11.1% (p=0.002) in the two lockdowns with a higher rate of ostomy and/or revision (+5.6%, p=0.219, and +10.2%, p=0.030). In-hospital mortality was increased in lockdown periods (1.64% vs 1.49%). In detail, mortality was identical in case of conservative treatment during lockdown periods (0.5%) but was higher in surgically treated patients (4.4% vs 3.6%). CONCLUSION: During lockdowns, there was an overall decrease of admissions for diverticulitis, especially non-emergency admissions in Germany, and treatment was more likely to be conservative. In case of surgery, however, there was increased risk of a complicated course (ostomy, re-surgery), possibly due to patient selection.
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COVID-19 , Diverticulite , Humanos , Estudos Retrospectivos , COVID-19/epidemiologia , Pandemias , Estudos de Coortes , Controle de Doenças Transmissíveis , Diverticulite/cirurgia , Hospitalização , Alemanha/epidemiologiaRESUMO
BACKGROUND: Colon conduit is an alternative approach to reconstructing the alimentary tract after esophagectomy. Hyperspectral imaging (HSI) has been demonstrated to be effective for evaluating the perfusion of gastric conduits, but not colon conduits. This is the first study to describe this new tool addressing image-guided surgery and supporting esophageal surgeons to select the optimal colon segment for the conduit and anastomotic site intraoperatively. PATIENTS AND METHODS: Of 10 patients, eight who underwent reconstruction with a long-segment colon conduit after esophagectomy between 01/05/2018 and 01/04/2022 were included in this study. HSI was recorded at the root and tip of the colon conduit after clamping the middle colic vessels, allowing us to evaluate the perfusion and appropriate part of the colon segment. RESULTS: Anastomotic leak (AL) was detected in only one (12.5%) of all the enrolled patients (n = 8). None of the patients developed conduit necrosis. Only one patient required re-anastomosis on postoperative day 4. No patient needed conduit removal, esophageal diversion, or stent placement. There was a change in the anastomosis site to proximal in two patients intraoperatively. There was no need to change the side of colon conduit intraoperatively in any patient. CONCLUSION: HSI is a promising and novel intraoperative imaging tool to objectively assess the perfusion of the colon conduit. It helps the surgeon to define the best perfused anastomosis site and the side of colon conduit in this type of operation.
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Esofagectomia , Imageamento Hiperespectral , Humanos , Colo/diagnóstico por imagem , Colo/cirurgia , Estômago , PerfusãoRESUMO
PURPOSE: In selected cases of severe Cushing's syndrome due to uncontrolled ACTH secretion, bilateral adrenalectomy appears unavoidable. Compared with unilateral adrenalectomy (for adrenal Cushing's syndrome), bilateral adrenalectomy has a perceived higher perioperative morbidity. The aim of the current study was to compare both interventions in endogenous Cushing's syndrome regarding postoperative outcomes. METHODS: We report a single-center, retrospective cohort study comparing patients with hypercortisolism undergoing bilateral vs. unilateral adrenalectomy during 2008-2021. Patients with adrenal Cushing's syndrome due to adenoma were compared with patients with ACTH-dependent Cushing's syndrome (Cushing's disease and ectopic ACTH production) focusing on postoperative morbidity and mortality as well as long-term survival. RESULTS: Of 83 patients with adrenalectomy for hypercortisolism (65.1% female, median age 53 years), the indication for adrenalectomy was due to adrenal Cushing's syndrome in 60 patients (72.2%; 59 unilateral and one bilateral), and due to hypercortisolism caused by Cushing's disease (n = 16) or non-pituitary uncontrolled ACTH secretion of unknown origin (n = 7) (27.7% of all adrenalectomies). Compared with unilateral adrenalectomy (n = 59), patients with bilateral adrenalectomy (n = 24) had a higher rate of severe complications (0% vs. 33%; p < 0.001) and delayed recovery (median: 10.2% vs. 79.2%; p < 0.001). Using the MTL30 marker, patients with bilateral adrenalectomy fared worse than patients after unilateral surgery (MTL30 positive: 7.2% vs. 25.0% p < 0.001). Postoperative mortality was increased in patients with bilateral adrenalectomy (0% vs. 8.3%; p = 0.081). CONCLUSION: While unilateral adrenalectomy for adrenal Cushing's syndrome represents a safe and definitive therapeutic option, bilateral adrenalectomy to control ACTH-dependent extra-adrenal Cushing's syndrome or Cushing's disease is a more complicated intervention with a mortality of nearly 10%.
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Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Adrenalectomia/efeitos adversos , Hormônio Adrenocorticotrópico , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Acute appendicitis is a global disease with high incidence. The main objective was to assess the association between time from admission to surgery (TAS) and surgery during emergency hours with operative outcome in light of conflicting evidence. METHODS: This is a retrospective population-wide analysis of hospital billing data (2010-2021) of all adult patient records of surgically treated cases of acute appendicitis in Germany by TAS. The primary outcome was a composite clinical endpoint (CCE; prolonged length of stay, surgical site infection, interventional draining after surgery, revision surgery, ICU admission and/or in-hospital mortality). Cases of complicated appendicitis were identified using diagnosis (ICD-10) and procedural codes (resection beyond appendectomy). RESULTS: 855 694 patient records were included, of which 27·6% (236,481) were complicated cases of acute appendicitis. 49·0% (418,821) were females and median age was 37 (interquartile range 22·5-51·5). Age, male sex, and comorbidity were associated with an increased proportion of CCE and in-hospital mortality. TAS was associated with a clinically relevant increase of CCE after 12 h in complicated appendicitis [Odd's ratio (OR), 1·19, 95% CI: 1·14-1·21] and after 24 h in uncomplicated appendicitis (OR 1·10, 95% CI: 1·02-1·19). Beyond the primary endpoint, the proportion of complicated appendicitis increased after TAS of 72 h. Surgery during emergency hours (6 pm-6.59 am) was associated with an increase of CCE and mortality (OR between 1·14 and 1·49). Age, female sex, night-time admission, weekend admission, a known previous surgery, obesity, and therapeutic anticoagulation were associated with delayed performance of surgery. CONCLUSION: This work found an increase of a CCE after TAS of 12 h for complicated appendicitis and an increase of the CCE after TAS of 24 h for uncomplicated appendicitis with a stable proportion of complicated appendicitis in these time windows. Both CCE and mortality were increased if appendectomy was performed during emergency hours.
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Apendicectomia , Apendicite , Humanos , Apendicite/cirurgia , Apendicite/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Apendicectomia/efeitos adversos , Alemanha/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Adulto Jovem , Mortalidade Hospitalar , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Estudos de Coortes , Fatores de TempoRESUMO
Objective: Postoperative pulmonary embolism (PE) is a rare but potentially life-threatening complication, which can be treated with extracorporeal membrane oxygenation (ECMO) therapy, a novel therapy option for acute cardiorespiratory failure. We postulate that hospitals with ECMO availability have more experienced staff, technical capabilities, and expertise in treating cardiorespiratory failure. Design: A retrospective analysis of surgical procedures in Germany between 2012 and 2019 was performed using hospital billing data. High-risk surgical procedures for postoperative PE were analyzed according to the availability of and expertise in ECMO therapy and its effect on outcome, regardless of whether ECMO was used in patients with PE. Methods: Descriptive, univariate, and multivariate analyses were applied to identify possible associations and correct for confounding factors (complications, complication management, and mortality). Results: A total of 13,976,606 surgical procedures were analyzed, of which 2,407,805 were defined as high-risk surgeries. The overall failure to rescue (FtR) rate was 24.4% and increased significantly with patient age, as well as type of surgery. The availability of and experience in ECMO therapy (defined as at least 20 ECMO applications per year; ECMO centers) are associated with a significantly reduced FtR in patients with PE after high-risk surgical procedures. In a multivariate analysis, the odds ratio (OR) for FtR after postoperative PE was significantly lower in ECMO centers (OR, 0.75 [0.70-0.81], P < 0.001). Conclusions: The availability of and expertise in ECMO therapy lead to a significantly reduced FtR rate of postoperative PE. This improved outcome is independent of the use of ECMO in these patients.
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BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is estimated to have claimed more than 6 million lives globally since it started in 2019. Germany was exposed to two waves of coronavirus disease 2019 in 2020, one starting in April and the other in October. To ensure sufficient capacity for coronavirus disease 2019 patients in intensive care units, elective medical procedures were postponed. The fraction of major abdominal cancer resections affected by these measures remains unknown, and the most affected patient cohort has yet to be identified. METHODS: This is a register-based, retrospective, nationwide cohort study of anonymized 'diagnosis-related group' billing data provided by the Federal Statistical Office in Germany. Cases were identified using diagnostic and procedural codes for major cancer resections. Population-adjusted cancer resection rates as the primary endpoint were compared at baseline (2012-2019) to those in 2020. RESULTS: A change in resection rates for all analyzed entities (esophageal, gastric, liver, pancreatic, colon, rectum, and lung cancer) was observed from baseline to 2020. Total monthly oncological resections dropped by 7.4% (8.7% normalized to the annual German population, P =0.011). Changes ranged from +3.7% for pancreatic resections ( P =0.277) to -19.4% for rectal resections ( P <0.001). Reductions were higher during lockdown periods. During the first lockdown period (April-June), the overall drop was 14.3% (8.58 per 100 000 vs. 7.35 per 100 000, P <0.001). There was no catch-up effect during the summer months except for pancreatic cancer resections. In the second lockdown period, there was an overall drop of 17.3%. In subgroup analyses, the elderly were most affected by the reduction in resection rates. There was a significant negative correlation between regional SARS-CoV-2 incidences and resections rates. This correlation was strongest for rectal cancer resections (Spearman's r : -0.425, P <0.001). CONCLUSIONS: The pandemic lockdowns had a major impact on the oncological surgical caseload in Germany in 2020. The elderly were most affected by the reduction. There was a clear correlation between SARS-CoV-2 incidences regionally and the reduction of surgical resection rates. In future pandemic circumstances, oncological surgery has to be prioritized with an extra focus on the most vulnerable patients.
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COVID-19 , Neoplasias Retais , Humanos , Idoso , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Estudos de Coortes , Pandemias , Controle de Doenças Transmissíveis , Alemanha/epidemiologiaRESUMO
BACKGROUND: Due to Covid-19, elective medical procedures were partly postponed to reduce the burden on the medical system. The impact of these effects in bariatric surgery and their individual consequences remain unknown. MATERIALS/METHODS: In a retrospective monocentric analysis, all bariatric patients at our centre between 01/2020 and 12/2021 were investigated. All patients with postponed surgery due to pandemic were analysed regarding weight change and metabolic parameters. In addition, we performed a nationwide cohort study of all bariatric patients in 2020 using billing data provided by the Federal Statistical Office. Population adjusted procedure rates of 2020 were compared to 2018/2019. RESULTS: Seventy-four patients (42.5%) out of 174 scheduled for bariatric surgery were postponed due to pandemic-related limitations, and 47 (63.5%) patients waited longer than 3 months. Mean postponement was 147.7 days. Apart from outliers (6.8% of all patients), mean weight (+0.9 kg) and body mass index (+0.3 kg/m2) remained stable. HbA1c increased significantly in patients with a postponement longer than 6 months (p = 0.024) and in diabetic patients (+0.18% vs -0.11 in non-diabetic, p = 0.042). In the Germany-wide cohort, the overall reduction of bariatric procedures in the first lockdown (04-06/2020) was -13.4% (p = 0.589). In the second lockdown (10-12/2020), there was no nationwide detectable reduction (+3.5%, p = 0.843) but inter-state differences. There was a catch-up in the interim months (+24.9%, p = 0.002). CONCLUSION: For future lockdowns or other healthcare bottleneck circumstances, the impact of postponement in bariatric patients has to be addressed and prioritization of vulnerable patients (e.g. diabetics) should be considered.
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Cirurgia Bariátrica , COVID-19 , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , COVID-19/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Controle de Doenças Transmissíveis , Alemanha/epidemiologiaRESUMO
OBJECTIVE: Adrenal resections are rare procedures of a heterogeneous nature. While recent European guidelines advocate a minimum annual caseload for adrenalectomies (6 per surgeon), evidence for a volume-outcome relationship for this surgery remains limited. DESIGN: A retrospective analysis of all adrenal resections in Germany between 2009 and 2017 using hospital billing data was performed. Hospitals were grouped into three tertiles of approximately equal patient volume. METHODS: Descriptive, univariate, and multivariate analyses were applied to identify a possible volume-outcome relationship (complications, complication management, and mortality). RESULTS: Around 17 040 primary adrenal resections were included. Benign adrenal tumors (n = 8,213, 48.2%) and adrenal metastases of extra-adrenal malignancies (n = 3582, 21.0%) were the most common diagnoses. Six hundred and thirty-two low-volume hospitals performed an equal number of resections as 23 high-volume hospitals (median surgeries/hospital/year 3 versus 31, P < .001). Complications were less frequent in high-volume hospitals (23.1% in low-volume hospitals versus 17.3% in high-volume hospitals, P < .001). The most common complication was bleeding in 2027 cases (11.9%) with a mortality of 4.6% (94 patients). Overall in-house mortality was 0.7% (n = 126). Age, malignancy, an accompanying resection, complications, and open surgery were associated with in-house mortality. In univariate analysis, surgery in high-volume hospitals was associated with lower mortality (OR: 0.47, P < .001). In a multivariate model, the tendency remained equal (OR: 0.59, P = .104). Regarding failure to rescue (death in case of complications), there was a trend toward lower mortality in high-volume hospitals. CONCLUSIONS: The annual caseload of adrenal resections varies considerably among German hospitals. Our findings suggest that surgery in high-volume centers is advantageous for patient outcomes although fatal complications are rare.
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Adrenalectomia , Humanos , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgiaRESUMO
Background: Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome. Methods: This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included. Results: A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different "low volume" hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different "high volume" hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications. Conclusion: Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals.
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Adrenalectomia , Hospitais com Baixo Volume de Atendimentos , Adolescente , Adrenalectomia/efeitos adversos , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The German Cancer Society (DKG) board certifies hospitals in treating esophageal, gastric, liver and pancreatic cancer among others. There has been no systematic verification of the number of major surgical resections set by DKG certification with regards to in-house mortality and failure to rescue (FtR). METHODS: This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). Inclusion criteria were based on the annual surgical minimum caseload (SMC) in accordance with DKG certification. RESULTS: 171,429 datasets were identified, including 31,140 esophageal, 54,155 gastric, 57,343 pancreatic and 28,791 liver resections. In-house mortality ranged from 6.2% for gastric resections to 8.1% for pancreatic resections. Differences in in-house mortality between hospitals which fulfilled SMC on average and those which did not fulfill SMC on average were 40.8% (5.3% vs 8.2%) for esophageal, 32.3% (4.8% vs 6.8%) for gastric and 45.7% (6.1% vs 9.8%) for pancreatic resections, while it was 8.2% higher in SMC-hospitals (7.6% vs 7.0%) for liver resections. Complication occurrence rates for esophageal, gastric and pancreatic resections were similar in SMC- and non-SMC-hospitals while FtR in hospitals fulfilling SMC was significantly lower. Data for liver resections demonstrated the same trends only in a sub-analysis of complex procedures. CONCLUSION: This study demonstrates an association between caseload threshold defined by DKG and lower mortality in esophageal, gastric, pancreatic and complex liver surgery. In these resections, FtR was reduced if SMC was fulfilled.
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Neoplasias Hepáticas , Complicações Pós-Operatórias , Gastrectomia , Mortalidade Hospitalar , Humanos , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461-induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC-interacting zinc-finger protein 1 (MIZ1)- and retinoblastoma protein (Rb)-dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine- and patient-derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside.
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Neoplasias Colorretais , RNA Polimerase I , Animais , Nucléolo Celular/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Camundongos , RNA Polimerase I/genética , Proteínas Ribossômicas/metabolismo , SenoterapiaRESUMO
Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%-local recurrence, 19% (n = 65)-distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.
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OBJECTIVE: Clinical evidence on giant intracranial aneurysms (GIAs), intracranial aneurysms with a diameter of at least 25 mm, is limited. The authors aimed to investigate the natural history, case fatality, and treatment outcomes of ruptured and unruptured GIAs. METHODS: In this international observational registry study, patients with a ruptured or unruptured GIA received conservative management (CM), surgical management (SM), or endovascular management (EM). The authors investigated rupture rates and case fatality. RESULTS: The retrospective cohort comprised 219 patients with GIAs (21.9% ruptured GIAs and 78.1% unruptured GIAs) whose index hospitalization occurred between January 2006 and November 2016. The index hospitalization in the prospective cohort (362 patients with GIAs [17.1% ruptured and 82.9% unruptured]) occurred between December 2008 and February 2017. In the retrospective cohort, the risk ratio for death at a mean follow-up of 4.8 years (SD 2.2 years) after CM, compared with EM and SM, was 1.63 (95% CI 1.23-2.16) in ruptured GIAs and 3.96 (95% CI 2.57-6.11) in unruptured GIAs. In the prospective cohort, the 1-year case fatality in ruptured GIAs/unruptured GIAs was 100%/22.0% during CM, 36.0%/3.0% after SM, and 39.0%/12.0% after EM. Corresponding 1-year rupture rates in unruptured GIAs were 25.0% during CM, 1.2% after SM, and 2.5% after EM. In unruptured GIAs, the HR for death within the 1st year in patients with posterior circulation GIAs was 6.7 (95% CI 1.5-30.4, p < 0.01), with patients with a GIA at the supraclinoid internal carotid artery as reference. Different sizes of unruptured GIAs were not associated with 1-year case fatality. CONCLUSIONS: Rupture rates for unruptured GIAs were high, and the natural history and treatment outcomes for ruptured GIAs were poor. Patients undergoing SM or EM showed lower case fatality and rupture rates than those undergoing CM. This difference in outcome may in part be influenced by patients in the CM group having been found poor candidates for SM or EM.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov).