Influence of Certification Program on Treatment Quality and Survival for Rectal Cancer Patients in Germany: Results of 13 Certified Centers in Collaboration with AN Institute.

INTRODUCTION: The certification of oncological units as colorectal cancer centers (CrCCs) has been proposed to standardize oncological treatment and improve the outcomes for patients with colorectal cancer (CRC). The proportion of patients with CRC in Germany that are treated by a certified center is around 53%. Lately, the effect of certification on the treatment outcomes has been critically discussed. AIM: Our aim was to investigate the treatment outcomes in patients with rectal carcinoma at certified CrCCs, in German hospitals of different medical care levels. METHODS: We performed a retrospective analysis of a prospective, multicentric database (AN Institute) of adult patients who underwent surgery for rectal carcinoma between 2002 and 2016. We included 563 patients from 13 hospitals of different medical care levels (basic, priority, and maximal care) over periods of 5 years before and after certification. RESULTS: The certified CrCCs showed a significant increase in the use of laparoscopic approach for rectal cancer surgery (5% vs. 55%, p < 0.001). However, we observed a significantly prolonged mean duration of surgery in certified CrCCs (161 Min. vs. 192 Min., p < 0.001). The overall morbidity did not improve (32% vs. 38%, p = 0.174), but the appearance of postoperative stool fistulas decreased significantly in certified CrCCs (2% vs. 0%, p = 0.036). Concerning the overall in-hospital mortality, we registered a positive trend in certified centers during the five-year period after the certification (5% vs. 3%, p = 0.190). The length of preoperative hospitalization (preop. LOS) was shortened significantly (4.71 vs. 4.13 days, p < 0.001), while the overall length of in-hospital stays was also shorter in certified CrCCs (20.32 vs. 19.54 days, p = 0.065). We registered a clear advantage in detailed, high-quality histopathological examinations regarding the N, L, V, and M.E.R.C.U.R.Y. statuses. In the performed subgroup analysis, a significantly longer overall survival after certification was registered for maximal medical care units (p = 0.029) and in patients with UICC stage IV disease (p = 0.041). In patients with UICC stage III disease, we registered a slightly non-significant improvement in the disease-free survival (UICC III: p = 0.050). CONCLUSIONS: The results of the present study indicate an improvement in terms of the treatment quality and outcomes in certified CrCCs, which is enforced by certification-specific aspects such as a more differentiated surgical approach, a lower rate of certain postoperative complications, and a multidisciplinary approach. Further prospective clinical trials are necessary to investigate the influence of certification in the treatment of CRC patients.

The Pancreas as a Target of Metastasis from Renal Cell Carcinoma: Is Surgery Feasible and Safe? A Single-Center Experience in a High-Volume and Certified Pancreatic Surgery Center in Germany.

Background: Secondary malignant tumors of the pancreas are rare, representing 2-5% of all pancreatic malignancies. Nevertheless, the pancreas is one of the target organs in cases of metastatic clear cell renal cell carcinoma (CCRCC). Additionally, recurrent metastasis may occur. Surgical resection remains the best and prognostically most favorable therapeutic option in cases of solitary pancreatic metastasis. Aim: To review retrospectively the clinical tumor registry of the University Hospital of Magdeburg, Germany, for this rare entity, performing a clinical systematic single-center observational study (design). Methods: A retrospective cohort analysis of consecutive patients who had undergone pancreatic resection for metastatic CCRC was performed in a single high-volume certified center for pancreatic surgery in Germany from 2010 to 2022. Results: All patients (n = 17) included in this study had a metachronous metastasis from a CCRCC. Surgery was performed at a median time interval of 12 (range, 9-16) years after primary resection for CCRCC. All 17 patients were asymptomatic at the time of diagnosis. Three of those patients (17.6%) presented with recurrent metastasis in a different part of the pancreas during follow-up. In a total of 17 patients, including those with recurrent disease, a surgical resection was performed; Pancreatoduodenectomy was performed in 6 patients (35%); left pancreatectomy with splenectomy was performed in 7 patients (41%). The rest of the patients underwent either a spleen-preserving pancreatic tail resection, local resection of the tumor lesion or a total pancreatectomy. The postoperative mortality rate was 6%. Concerning histopathological findings, seven patients (41%) had multifocal metastasis. An R0 resection could be achieved in all cases. The overall survival at one, three and five years was 85%, 85% and 72%, respectively, during a median follow-up of 43 months. Conclusions: CCRC pancreatic metastases can occur many years after the initial treatment of the primary tumor. Surgery for such a malignancy seems feasible and safe; it offers very good short- and long-term outcomes, as indicated. A repeated pancreatic resection can also be safely performed.

NETworking for Health and in Disease: Neutrophil Extracellular Traps in Pediatric Surgical Care.

This comprehensive review examines the role of Neutrophil Extracellular Traps (NETs) in pediatric surgery. Focusing on NET formation, functions, and implications, this study highlights their dual impact in infection control and contribution to tissue damage after surgery. It covers the role of NET formation in a range of pediatric conditions including immunothrombosis, formation of peritoneal adhesions, appendicitis, burns, gallstones, tumors, and necrotizing enterocolitis (NEC). The results underscore the significance of NETs in fighting infections and their association with complications like sepsis and delayed wound healing. The breakdown products of NETs as a diagnostic tool of the clinical course of acute appendicitis will also be discussed. Understanding NET formation in the pathophysiology can potentially help to find new therapeutic approaches such as the application of DNase and elastase inhibitors to change the clinical course of various diseases in pediatric surgery such as improvement of wound healing, adhesion formation, NEC, and many more.

Management of acute appendicitis during COVID-19 pandemic. Single center data from a tertiary care hospital in Germany.

Objectives: The unexpected global overload of the health system during COVID-19 pandemic has caused changes in management of acute appendicitis worldwide. Whereas conservative treatment was widely recommended, the appendicectomy remained standard therapy in Germany. We aimed to investigate the impact of COVID-19 pandemic on treatment routine for acute appendicitis at University Hospital of Magdeburg. Methods: Adult patients with clinical and/or radiological diagnosis of acute appendicitis were included in the single center retrospective study. Data was collected to patient demographics, treatment modality and outcomes including morbidity and length of stay. The patient data related to COVID-19 period from March 22, 2020 to December 31, 2021 (649 days) were compared to the Non-COVID-19 period from June 12, 2018 to March 21, 2020 (649 days). Subgroup analysis related to conservative or surgical treatment has been performed. Results: A total of 385 patients was included in the study, 203 (52.73 %) during Non-COVID-19 period and 182 (47.27 %) during COVID-19 period. Mean age of entire collective was 43.28 years, containing 43.9 % female patients (p=0.095). Conservative treatment was accomplished in 49 patients (12.7 % of entire collective), increasing from 9.9 % to 15.9 % during COVID-19 period (p=0.074). Laparoscopic appendicectomy was performed in 99.3 % (n=152) of operated patients during COVID-19 period (p=0.013), followed by less postoperative complications compared to reference period (23.5 % vs. 13.1 %, p=0.015). The initiation of antibiotic therapy after the diagnosis increased from 37.9 % to 53.3 % (p=0.002) during COVID-19 period regardless the following treatment modality. Antibiotic treatment showed shorter duration during pandemic period (5.57 days vs. 3.16 days, p<0.001) and it was given longer in the conservative treatment group (5.63 days vs. 4.26 days, p=0.02). The overall length of stay was shorter during COVID-19 period (4.67 days vs. 4.12 days, p=0.052) and in the conservative treatment group (3.08 days vs. 4.47 days, p<0.001). However, the overall morbidity was lower during the COVID-19 period than before (17.2 % vs. 7.7 %, p=0.005) and for conservative therapy compared to appendicectomy (2 % vs. 14.3 %, p=0.016). There was no mortality documented. Conclusions: According to our findings the COVID-19 pandemic had a relevant impact on treatment of acute appendicitis, but it was possible to maintain the traditional diagnostic and treatment pathway. Although laparoscopic appendicectomy remains a recommended procedure, the conservative treatment of uncomplicated appendicitis with excellent short-term outcome can be a safe alternative to surgery during potential new wave of COVID-19 pandemic and in the daily routine.

Moonlighting chromatin: when DNA escapes nuclear control.

Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable.

COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma.

Background: Treatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma. Methods: Several public databases had been screened to observe COL10A1 expression in transcriptome levels with cell lines and tissues. Protein interactions and alignment to changes in clinical parameters and immune cell invasion were performed, too. We also used algorithms to build a novel COL10A1-related immunomodulator signature. Various wet-lab experiments were conducted to quantify COL10A1 protein and transcript expression levels in disease and control cell models. Results: COL10A1 mRNA levels in tumor material is clinical and molecular prognostic, featuring upregulation compared to non-cancer tissue, increase with histomorphological malignancy grading of the tumor, elevation in tumors that invade perineural areas, or lymph node invasion. Transcriptomic alignment noted a strong positive correlation of COL10A1 with transcriptomic signature of cancer-associated fibroblasts (CAFs) and populations of the immune compartment, namely, B cells and macrophages. We verified those findings in functional assays showing that COL10A1 are decreased in CRC cells compared to fibroblasts, with strongest signal in the cell supernatant of the cells. Conclusion: COL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment.

[Influence of the COVID-19 pandemic on robotic visceral surgery in Germany]. / Auswirkungen der COVID-19-Pandemie auf die robotische Viszeralchirurgie in Deutschland.

BACKGROUND: Robotic procedures are gaining more and more importance in visceral surgery and seem to develop into an indispensable tool in minimally invasive visceral surgery. In 2020 the COVID-19 pandemic caused unexpected changes in daily surgical routines with still ongoing challenges. We evaluated the impact of the COVID-19 pandemic on robotic visceral procedures and the associated training provided in Germany. MATERIAL AND METHODS: We performed a thorough evaluation of German hospitals and identified 89 surgical departments performing robotic visceral procedures. After extensive topic-related literature search an online questionnaire was developed. It included 35 questions referring to all relevant topics on robotic surgery, such as training programs and influence of the COVID-19 pandemic. The survey was sent via email three times to each department. Descriptive and subgroup analysis were performed. RESULTS: We reported a response to our questionnaire from 22 (24.7%) surgical departments and17 questionnaires were analyzable. The vast majority of them weresurgical departments of university hospitals (58.8%), 17.6% maximum care clinics and 23.5% main care clinics. Robotic procedures were performed for the upper gastrointestinal tract (UGI 88.2%), the hepatopancreaticobiliary system (HPB 82.4%), in the colorectal region (94.1%) and for hernias (35.3%). The relative proportion of robotic operations in comparison to all visceral procedures was between 0.3% and 15.4%. The average conversion rate was 4.6 ± 3.2% referring to 2020. All participating clinics used the robotic DaVinci® system (Intuitive Surgical Inc., CA, USA). In summary 22 robotic systems were used mainly in an interdisciplinary setting (82.4%). For teaching purposes, 7 departments (41.2%) provided a second robotic console. On average 13.2 ± 6.5% of surgeons per clinic were involved in robotic procedures. Defined operating room (OR) teams (82.4%) consisted of consultants, specialists and residents. Team training for surgeons and OR nurses was mainly (52.9%) based on clinic-specific programs. Due to the COVID-19 pandemic the number of robotic procedures decreased in 70.0% of the participating departments compared to 2019 with the highest decline reported during the second quarter of 2020 (64.7%). Referring to this, staff shortage of non-surgical disciplines (anesthesiologists 35.3%, OR nurses 35.3%, intensive care medics 17.6%), COVID-19-specific regulations (58.8%) and limited capacities of intensive and intermediate care (47.1%) were specified as underlying causes. Due to the COVID-19 pandemic, caused by a decline in numbers of robotic procedures, robotic training was paused completely in assistance at the operating table in 23.5% and at the second console in 42.9%. CONCLUSION: Robotic visceral surgery is already implemented with a broad spectrum of operations in many German clinics of different care levels; however, the relative proportion of robotic procedures is low, when compared to the overall caseload of each clinic. Training concepts are heterogeneous and focused on experts. In surgeons with growing experience in robotic surgery, conversion rates are recorded to be very low. There was a negative impact on robotic case numbers and training provided in 2020 caused by the COVID-19 pandemic. Therefore, a further endorsement of robotic training programs and an improvement of training designs seem to be essential tools in order to enforce robotic procedures in visceral surgery.

Laparoscopic cholecystectomy during the COVID-19 pandemic in a tertiary care hospital in Germany: higher rates of acute and gangrenous cholecystitis in elderly patients.

BACKGROUND: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany. PATIENTS AND METHODS: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year. RESULTS: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality. CONCLUSION: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly.

Hypoxia Promotes Neutrophil Survival After Acute Myocardial Infarction.

Phagocytosis, degranulation, and neutrophil extracellular traps (NETs) formation build the armory of neutrophils for the first line of defense against invading pathogens. All these processes are modulated by the microenvironment including tonicity, pH and oxygen levels. Here we investigated the neutrophil infiltration in cardiac tissue autopsy samples of patients with acute myocardial infarction (AMI) and compared these with tissues from patients with sepsis, endocarditis, dermal inflammation, abscesses and diseases with prominent neutrophil infiltration. We observed many neutrophils infiltrating the heart muscle after myocardial infarction. Most of these had viable morphology and only few showed signs of nuclear de-condensation, a hallmark of early NET formation. The abundance of NETs was the lowest in acute myocardial infarction when compared to other examined diseases. Since cardiac oxygen supply is abruptly abrogated in acute myocardial infarction, we hypothesized that the resulting tissue hypoxia increased the longevity of the neutrophils. Indeed, the viable cells showed increased nuclear hypoxia inducible factor-1α (HIF-1α) content, and only neutrophils with low HIF-1α started the process of NET formation (chromatin de-condensation and nuclear swelling). Prolonged neutrophil survival, increased oxidative burst and reduced NETs formation were reproduced under low oxygen tensions and by HIF-1α stabilization in vitro. We conclude that nuclear HIF-1α is associated with prolonged neutrophil survival and enhanced oxidative stress in hypoxic areas of AMI.