Die Prävalenz von Lymphknotenmetastasen und prognostische Faktoren bezogen auf das Langzeitüberleben nach pulmonaler Metastasektomie bei kolorektalem Karzinom

Ziel dieser Studie war es, die Prävalenz von thorakalen Lymphknotenmetastasen und das Langzeitüberleben, als auch prognostische Faktoren, bei Patienten die eine systematische Lymphknotendissektion und eine pulmonale Metastasektomie bei kolorektalem Karzinom erhielten zu untersuchen. Hierbei wurden retrospektiv die prospektiven Daten von allen Patienten mit kolorektalem Karzinom, die von 1999 bis 2009, in kurativer Absicht an pulmonalen Metastasen inklusiver systematischer Lymphknotendissektion operiert wurden untersucht. Die Prävalenz der Lymphknotenmetastasen lag bei 22,4%. Lymphknotenmetastasen wurden häufiger bei einer Primärtumorlokalisation im Rektum (30,2% Rektum vs. 11,6% Kolon, p= 0,005), bei anatomischen Segment-/ Lappenresektionen (27,5% Anatomische Segmentresektion oder Lobektomie vs. 12,5% Keil-/ Laserresektion, p= 0,031) und bei einem Vorhandensein von mehr als 10 Lungenmetastasen gefunden (45,5% Anzahl der Metastasen ≥ 10 vs. 20,8% bei 1-9 Metastasen, p= 0,071). Das mediane Überleben für alle Patienten lag bei 64 Monaten. Lymphknotenmetastasen waren mit einem geringerem, aber vielversprechendem Langzeitüberleben assoziiert (44 vs. 78 Monate, p= 0,03). Die Primärtumorlokalisation im Rektum, der M-Status des Primärtumors, die thorakale Lymphknotenmetastasierung und ein Progress der Erkrankung bei präoperativer Chemotherapie vor Metastasektomie waren unabhängige signifikante Prognosefaktoren beim Langzeitüberleben. Keinen signifikanten Unterschied zeigte die Metastasierungsart bei syn- oder metachronen Lungen- und Lebermetastasen (nur Lunge 78 Monate, metachron Lunge und Leber 74 Monate, synchron Lunge und Leber 63 Monate p= 0,527). Bei unserem Patientengut waren 66% der Resektionen anatomische Segmentresektionen und Lobektomien, wobei keine Laser- oder Keilresektion möglich waren. Damit fordert die Wachstumsform der Metastase eine Lymphknotendissektion, da eine Segmentresektion und Lobektomie nur über eine Lymphknotendissektion möglich sind. Zusammenfassend zeigt diese Studie, dass Lymphknotenmetastasen mit einem geringeren, aber vielversprechendem Langzeitüberleben assoziiert sind, welches eine konsequente Metastasenresektion bei einem ausgewählten Patientengut begründet (medianes Überleben 44 Monate). Eine routinemäßige systematische Lymphknotendissektion als Kompartmentdissektion, zur kompletten Resektion der Metastasen, sollte aufgrund der hohen Prävalenz von thorakalen Lymphknotenmetastasen insbesondere bei einer Primärtumorlokalisation im Rektum, im Falle von notwendigen anatomischen Resektionen und bei einer hohen Anzahl an Lungenmetastasen durchgeführt werden. Die Primärtumorlokalisation im Rektum, der M-Status des Primärtumors, die Anzahl vorhandener thorakaler Lymphknotenmetastasen und ein Progress der Erkrankung bei präoperativer Chemotherapie vor Metastasektomie waren unabhängige negative Prognosefaktoren auf das Überleben

Impact of an in-hospital endocarditis team and a state-wide endocarditis network on perioperative outcomes

Background: Infective endocarditis (IE) requires multidisciplinary management. We established an endocarditis team within our hospital in 2011 and a state-wide endocarditis network with referring hospitals in 2015. We aimed to investigate their impact on perioperative outcomes. Methods: We retrospectively analyzed data from patients operated on for IE in our center between 01/2007 and 03/2018. To investigate the impact of the endocarditis network on referral latency and pre-operative complications we divided patients into two eras: before ( n = 409) and after ( n = 221) 01/2015. To investigate the impact of the endocarditis team on post-operative outcomes we conducted multivariate binary logistic regression analyses for the whole population. Kaplan–Meier estimates of 5-year survival were reported. Results: In the second era, after establishing the endocarditis network, the median time from symptoms to referral was halved (7 days (interquartile range: 2–19) vs. 15 days (interquartile range: 6–35)), and pre-operative endocarditis-related complications were reduced, i.e., stroke (14% vs. 27%, p < 0.001), heart failure (45% vs. 69%, p < 0.001), cardiac abscesses (24% vs. 34%, p = 0.018), and acute requirement of hemodialysis (8% vs. 14%, p = 0.026). In both eras, a lack of recommendations from the endocarditis team was an independent predictor for in-hospital mortality (adjusted odds ratio: 2.12, 95% CI: 1.27–3.53, p = 0.004) and post-operative stroke (adjusted odds ratio: 2.23, 95% CI: 1.12–4.39, p = 0.02), and was associated with worse 5-year survival (59% vs. 40%, log-rank < 0.001). Conclusion: The establishment of an endocarditis network led to the earlier referral of patients with fewer pre-operative endocarditis-related complications. Adhering to endocarditis team recommendations was an independent predictor for lower post-operative stroke and in-hospital mortality, and was associated with better 5-year survival

Short-term and long-term outcomes after resection of thoracic growing teratoma syndrome

PURPOSE Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available. METHODS We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan-Meier method. RESULTS Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19-50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13-237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively. CONCLUSIONS TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection

Abstract Introduction and objectives Postchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery. Patients and methods From a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy. Results All patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%. Conclusion The data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen

Pulmonary Resection after Radiosurgery and Neoadjuvant Immunochemotherapy for NSCLC Patients with Synchronous Brain Metastasis—A Case Series of Three Patients

Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches

Pulmonary Resection after Radiosurgery and Neoadjuvant Immunochemotherapy for NSCLC Patients with Synchronous Brain Metastasis&mdash;A Case Series of Three Patients

Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches

Impact of higher-order heme degradation products on hepatic function and hemodynamics

Background & Aims: Biliverdin and bilirubin were previously considered end products of heme catabolism; now, however, there is evidence for further degradation to diverse bioactive products. Z-BOX A and Z-BOX B arise upon oxidation with unknown implications for hepatocellular function and integrity. We studied the impact of Z-BOX A and B on hepatic functions and explored their alterations in health and cholestatic conditions. Methods: Functional implications and mechanisms were investigated in rats, hepatocytic HepG2 and HepaRG cells, human immortalized hepatocytes, and isolated perfused livers. Z-BOX A and B were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in acute and acute-on-chronic liver failure and hereditary unconjugated hyperbilirubinemia. Results: Z-BOX A and B are found in similar amounts in humans and rodents under physiological conditions. Serum concentrations increased similar to 20-fold during cholestatic liver failure in humans (p <0.001) and in hereditary deficiency of bilirubin glucuronidation in rats (p <0.001). Pharmacokinetic studies revealed shorter serum half-life of Z-BOX A compared to its regio-isomer Z-BOX B (p = 0.035). While both compounds were taken up by hepatocytes, Z-BOX A was enriched similar to 100-fold and excreted in bile. Despite their reported vasoconstrictive properties in the brain vasculature, BOXes did not affect portal hemodynamics. Both Z-BOX A and B showed dose-dependent cytotoxicity, affected the glutathione redox state, and differentially modulated activity of Rev-erba and Rev-erbb. Moreover, BOXes-triggered remodeling of the hepatocellular cytoskeleton. Conclusions: Our data provide evidence that higher-order heme degradation products, namely Z-BOX A and B, impair hepatocellular integrity and might mediate intra-and extrahepatic cytotoxic effects previously attributed to hyperbilirubinemia. Lay summary: Degradation of the blood pigment heme yields the bile pigment bilirubin and the oxidation products Z-BOX A and Z-BOX B. Serum concentrations of these bioactive molecules increase in jaundice and can impair liver function and integrity. Amounts of Z-BOX A and Z-BOX B that are observed during liver failure in humans have profound effects on hepatic function when added to cultured liver cells or infused into healthy rats. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V

Genetic Factors of the Disease Course After Sepsis: Rare Deleterious Variants Are Predictive

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. For its clinical course, host genetic factors are important and rare genomic variants are suspected to contribute. We sequenced the exomes of 59 Greek and 15 German patients with bacterial sepsis divided into two groups with extremely different disease courses. Variant analysis was focusing on rare deleterious single nucleotide variants (SNVs). We identified significant differences in the number of rare deleterious SNVs per patient between the ethnic groups. Classification experiments based on the data of the Greek patients allowed discrimination between the disease courses with estimated sensitivity and specificity &gt; 75%. By application of the trained model to the German patients we observed comparable discriminatory properties despite lower population-specific rare SNV load. Furthermore, rare SNVs in genes of cell signaling and innate immunity related pathways were identified as classifiers discriminating between the sepsis courses. Sepsis patients with favorable disease course after sepsis, even in the case of unfavorable preconditions, seem to be affected more often by rare deleterious SNVs in cell signaling and innate immunity related pathways, suggesting a protective role of impairments in these processes against a poor disease course

Cytokine Hemoadsorption During Cardiac Surgery Versus Standard Surgical Care for Infective Endocarditis (REMOVE): Results From a Multicenter Randomized Controlled Trial

BACKGROUND: Cardiac surgery often represents the only treatment option in patients with infective endocarditis (IE). However, IE surgery may lead to a sudden release of inflammatory mediators, which is associated with postoperative organ dysfunction. We investigated the effect of hemoadsorption during IE surgery on postoperative organ dysfunction. METHODS: This multicenter, randomized, nonblinded, controlled trial assigned patients undergoing cardiac surgery for IE to hemoadsorption (integration of CytoSorb to cardiopulmonary bypass) or control. The primary outcome (change in sequential organ failure assessment score [Delta SOFA]) was defined as the difference between the mean total postoperative SOFA score, calculated maximally to the 9th postoperative day, and the basal SOFA score. The analysis was by modified intention to treat. A predefined intergroup comparison was performed using a linear mixed model for Delta SOFA including surgeon and baseline SOFA score as fixed effect covariates and with the surgical center as random effect. The SOFA score assesses dysfunction in 6 organ systems, each scored from 0 to 4. Higher scores indicate worsening dysfunction. Secondary outcomes were 30-day mortality, duration of mechanical ventilation, and vasopressor and renal replacement therapy. Cytokines were measured in the first 50 patients. RESULTS: Between January 17, 2018, and January 31, 2020, a total of 288 patients were randomly assigned to hemoadsorption (n=142) or control (n=146). Four patients in the hemoadsorption and 2 in the control group were excluded because they did not undergo surgery. The primary outcome, Delta SOFA, did not differ between the hemoadsorption and the control group (1.79 +/- 3.75 and 1.93 +/- 3.53, respectively; 95% CI, -1.30 to 0.83; P=0.6766). Mortality at 30 days (21% hemoadsorption versus 22% control; P=0.782), duration of mechanical ventilation, and vasopressor and renal replacement therapy did not differ between groups. Levels of interleukin-1 beta and interleukin-18 at the end of integration of hemoadsorption to cardiopulmonary bypass were significantly lower in the hemoadsorption than in the control group. CONCLUSIONS: This randomized trial failed to demonstrate a reduction in postoperative organ dysfunction through intraoperative hemoadsorption in patients undergoing cardiac surgery for IE. Although hemoadsorption reduced plasma cytokines at the end of cardiopulmonary bypass, there was no difference in any of the clinically relevant outcome measures