Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising. METHODS: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints. DISCUSSION: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial. ETHICS AND DISSEMINATION: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives. TRIAL REGISTRATION NUMBER: DRKS00027474.

Altered serum metabolome as an indicator of paraneoplasia or concomitant cancer in patients with rheumatic disease.

OBJECTIVES: A timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both cancer and RMD, we analysed if a metabolic signature can indicate paraneoplasia (PN) or reveal concomitant cancer in patients with RMD. METHODS: Metabolic alterations in the sera of rheumatoid arthritis (RA) patients with (n=56) or without (n=52) a history of invasive cancer were quantified by nuclear magnetic resonance analysis. Metabolites indicative of cancer were determined by multivariable regression analyses. Two independent RA and spondyloarthritis (SpA) cohorts with or without a history of invasive cancer were used for blinded validation. Samples from patients with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, non-invasive (NI) precancerous lesions and non-melanoma skin cancer and systemic lupus erythematosus and samples prior to the development of malignancy were used to test the model performance. RESULTS: Based on the concentrations of acetate, creatine, glycine, formate and the lipid ratio L1/L6, a diagnostic model yielded a high sensitivity and specificity for cancer diagnosis with AUC=0.995 in the model cohort, AUC=0.940 in the blinded RA validation cohort and AUC=0.928 in the mixed RA/SpA cohort. It was equally capable of identifying cancer in patients with PN. The model was insensitive to common demographic or clinical confounders or the presence of NI malignancy like non-melanoma skin cancer. CONCLUSIONS: This new set of metabolic markers reliably predicts the presence of cancer in arthritis or PN patients with high sensitivity and specificity and has the potential to facilitate a rapid and correct diagnosis of malignancy.

Risk factors for long-term mortality after acute aortic dissection-results of the German registry for acute aortic dissection type a long-term follow-up.

OBJECTIVES: Several short-term analyses from German Registry for Acute Aortic Dissection Type A (GERAADA) have been published. This study investigated whether short-term risk factors are transferable to the long-term prognosis of patients. METHODS: Thirty-three centres with 2686 patients participated in the long-term follow-up. A total of 1164 patients died, 1063 survived and 459 were lost to follow-up during the follow-up timeframe (mean duration: 10.2 years). Long-term mortality of the cohort was compared with an age-stratified, German population. RESULTS: One, 5 and 10 years after initial surgery, the survival of the GERAADA patient cohort was 71.4%, 63.4% and 51%, respectively. Without the early deaths (90-day mortality 25.4%), survival was calculated after 1, 5 and 10 years: 95.6%, 83.5% and 68.3%. Higher age, longer extracorporeal circulation time, shorter perioperative ventilation time and postoperative neurologic deficits were predictive of long-term prognosis. In an age-divided landmark analysis, the mortality of aortic dissection surgery survivors was found to be similar to that of the general German population. If patients are sorted in risk groups according to the GERAADA score, long-term survival differs between the risk groups. CONCLUSIONS: If patients have survived an acute postoperative period of 90 days, life expectancy comparable to that of the general German population can be assumed in lower- and medium-risk patients. Whether the GERAADA score can provide valuable insights into the long-term prognosis of patients undergoing surgery for acute aortic dissection type A is still unclear.

Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials.

PURPOSE: Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS: Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS: A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group (P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION: Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

BACKGROUND: Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS: We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS: Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS: Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

Introduction: Studies have shown that pregnant women with COVID-19 have a higher risk of intensive care unit admission and invasive mechanical ventilation support than non-pregnant women. Pregnancy-associated physiological changes in respiratory function may contribute to the elevated risk. Alteration in lung volumes and capacities are attributed to the mechanical impediment caused by the growing fetus. Multiple pregnancies may therefore compromise functional lung capacity earlier than singleton pregnancies and contribute to severe respiratory symptoms of COVID-19. Materials and Methods: A total of 5514 women with a symptomatic SARS-CoV-2 infection during pregnancy registered in the COVID-19 Related Obstetric and Neonatal Outcome Study were included. The COVID-19-related adverse maternal outcomes were compared in 165 multiple versus 5349 singleton pregnancies. Combined adverse maternal outcome was defined as presence of COVID-19-related hospitalization and/or pneumonia and/or oxygen administration and/or transfer to ICU and/or death. Multivariate logistic regression was used to estimate the odds ratios and 95% confidence intervals were calculated. Results: The frequency of dyspnea, likelihood of developing dyspnea in a defined pregnancy week and duration of the symptomatic phase of the COVID-19 infection did not differ between the two groups. On average, COVID-19-related combined adverse outcome occurred earlier during pregnancy in women expecting more than one child than in singleton pregnancies. The overall incidence of singular and combined COVID-19-associated adverse maternal outcomes was not significantly different between groups. However, regression analysis revealed that multiple gestation, preconceptional BMI > 30 kg/m 2 and gestational age correlated significantly with an increased risk of combined adverse maternal outcome. Conversely, maternal age and medically assisted reproduction were not significant risk factors for combined adverse maternal outcome. Conclusion: Our data show that multiple gestation alone is a risk factor for COVID-19-associated combined adverse maternal outcome. Moreover, severe courses of COVID-19 in women expecting more than one child are observed earlier in pregnancy than in singleton pregnancies.

Impact of circumferential resection margin on survival in ampullary cancer: retrospective analysis.

BACKGROUND: Ampullary carcinoma is a clinically variable entity. This study aimed to evaluate prognostic factors for the outcome of resected ampullary carcinoma patients with particular intent to analyse the influence of surgical radicality. METHODS: Patients undergoing resection between 2002 and 2017 were analysed. Clinicopathological parameters, perioperative outcome and survival were examined. Risk factor analysis for postresection survival was performed. Resection margin status was evaluated according to the revised classification for pancreatic adenocarcinoma. RESULTS: A total of 234 patients were identified, 97.9 per cent (n = 229) underwent formal resection, while 2.1 per cent (n = 5) underwent ampullary resection. Histological subtypes were 46.6 per cent (n = 109) pancreatobiliary, 34.2 per cent (n = 80) intestinal, 11.5 per cent (n = 27) mixed, and 7.7 per cent (n = 18) undetermined. In the pancreatobiliary group, tumours were more advanced with more vascular resections, pT4 stage, G3 differentiation and pN+ status. Five-year overall survival was significantly different for pancreatobiliary compared to intestinal (51.7 per cent versus 72.8 per cent, P = 0.0087). In univariable analysis, age, pT4 stage, pN+, pancreatobiliary subtype and positive resection margin were significantly associated with worse overall survival. Long-term outcome was significantly better after true R0 resection (circumferential resection margin-, tumour clearance >1 mm) compared with circumferential resection margin+ (<1 mm) and R1 resections (5-year overall survival: 69.6 per cent, median overall survival 191 months versus 42.4 per cent and 53 months; P = 0.0017). CONCLUSION: Postresection survival of ampullary carcinoma patients is determined by histological subtype and surgical radicality. Intestinal differentiation is associated with less advanced tumour stages and better differentiation, which is reflected in a significantly better overall survival compared to pancreatobiliary differentiation. Despite this, true R0-resection is a prognostic key determinant in both entities, achieving 5-year survival in two-thirds of patients.

Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events.

BACKGROUND: Rheumatic immune-related adverse events (R-irAEs) occur in 5-15% of patients receiving immune checkpoint inhibitors (ICI) and, unlike other irAEs, tend to be chronic. Herein, we investigate the factors influencing cancer and R-irAEs outcomes with particular focus on adverse effects of anti-inflammatory treatment. METHODS: In this prospective, multicenter, long-term, observational study, R-irAEs were comprehensively analyzed in patients with malignant melanoma (MM, n=50) and non-small cell lung cancer (NSCLC, n=41) receiving ICI therapy who were enrolled in the study between August 1, 2018, and December 11, 2022. RESULTS: After a median follow-up of 33 months, progressive disease or death occurred in 66.0% and 30.0% of MM and 63.4% and 39.0% of patients with NSCLC. Male sex (progression-free survival (PFS): p=0.013, and overall survival (OS): p=0.009), flare of a pre-existing condition (vs de novo R-irAE, PFS: p=0.010) and in trend maximum glucocorticoid (GC) doses >10 mg and particularly ≥1 mg/kg prednisolone equivalent (sex-adjusted PFS: p=0.056, OS: p=0.051) were associated with worse cancer outcomes. Patients receiving disease-modifying antirheumatic drugs (DMARDs) showed significantly longer PFS (n=14, p=0.011) and OS (n=20, p=0.018). Effects of these variables on PFS and/or OS persisted in adjusted Cox regression models. Additionally, GC treatment negatively correlated with the time from diagnosis of malignancy and the latency from ICI start until R-irAE onset (all p<0.05). R-irAE features and outcomes were independent of other baseline patient characteristics in both studied cancer entities. CONCLUSION: Male sex, flare of pre-existing rheumatologic conditions and extensive GC treatment appeared to be linked with unfavorable cancer outcomes, while DMARD use had a favorable impact. These findings challenge the current dogma of restrictive DMARD use for R-irAE and thus may pave the way to better strategies and randomized controlled trials for the growing number of patients with R-irAE.

Primary Care Disease Management for Venous Leg Ulceration in German Healthcare: Results of the Ulcus Cruris Care Pilot Study.

Despite proven effectiveness, compression therapy is applied in only 20-40% of patients with venous leg ulceration, leading to avoidable chronification and morbidity. The Ulcus Cruris Care project was established to develop a new disease-management concept comparable to existing programs for chronic diseases to support evidence-based treatment of venous leg ulceration. This prospective controlled study assessed its first implementation. Interventional elements comprised online training for general practitioner practices, software support for case management, and educational materials for patients. A total of 20 practices and 40 patients were enrolled in a 1:1 ratio to the intervention and control group. Guideline-conform compression therapy was applied more frequently in the intervention group (19/20 [95%] vs. 11/19 [58%]; p = 0.006). For patients with ulcers existing ≤ 6 months, the healing rate at 12 weeks was 8/11 [73%] (intervention) compared to 4/11 [36%] (control; p = 0.087). Patients after intervention had higher scores for self-help and education in the PACIC-5A questionnaire (42.9 ± 41.6 vs. 11.4 ± 28.8; p = 0.044). Treatment costs were EUR 1.380 ± 1.347 (intervention) and EUR 2.049 ± 2.748 (control; p = 0.342). The results of this study indicate that the Ulcus Cruris Care intervention may lead to a significant improvement in care. Consequently, a broader rollout in German healthcare seems warranted.

Conventional specimen radiography in breast-conserving therapy: a useful tool for intraoperative margin assessment after neoadjuvant therapy?

PURPOSE: A previous study in our breast unit showed that the diagnostic accuracy of intraoperative specimen radiography and its potential to reduce second surgeries in a cohort of patients treated with neoadjuvant chemotherapy were low, which questions the routine use of Conventional specimen radiography (CSR) in this patient group. This is a follow-up study in a larger cohort to further evaluate these findings. METHODS: This retrospective study included 376 cases receiving breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. CSR was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. RESULTS: 362 patients with 2172 margins were assessed. The prevalence of positive margins was 102/2172 (4.7%). CSR had a sensitivity of 37.3%, a specificity of 85.6%, a positive predictive value (PPV) of 11.3%, and a negative predictive value (NPV) of 96.5%. The rate of secondary procedures was reduced from 75 to 37 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 10. In the subgroup of patients with clinical complete response (cCR), the prevalence of positive margins was 38/1002 (3.8%), PPV was 6.5% and the NNT was 34. CONCLUSION: This study confirms our previous finding that the rate of secondary surgeries cannot be significantly reduced by CSR-guided intraoperative re-excisions in cases with cCR after NACT. The routine use CSR after NACT is questionable, and alternative tools of intraoperative margin assessment should be evaluated.

Conventional partial pancreatoduodenectomy versus an extended pancreatoduodenectomy (triangle operation) for pancreatic head cancers-study protocol for the randomised controlled TRIANGLE trial.

BACKGROUND: Pancreatic ductal carcinoma (PDAC) is the fourth most frequent cause of cancer-related death in the Western world, and its incidence is rising. In patients that undergo curative resection, local recurrence (LR) is frequent. A recently described surgical technique of extended pancreatoduodenectomy (PD) termed the TRIANGLE operation has been proposed as a promising approach to reduce LR and improve disease-free survival in PDAC patients. METHODS: The TRIANGLE trial is a multicentre confirmatory randomised controlled superiority trial with two parallel study groups. A total of 270 patients with suspected or histologically confirmed pancreatic head cancer scheduled for PD will be included in the trial and randomly assigned to the intervention group (extended PD defined as Inoue level 3 dissection along the superior mesenteric and celiac artery as well as removal of all soft tissue in the so-called triangle between the celiac artery, the SMA and the mesenterico-portal axis) or the control group (conventional PD with lymphadenectomy and removal of soft tissue according to current guidelines). The primary endpoint of the trial will be the disease-free survival of patients. Other perioperative outcomes as well as oncological parameters and patient-reported outcomes will be analysed as secondary outcomes. DISCUSSION: Despite multimodal treatment, LR remains high and disease-free survival is limited following PD for PDAC. The TRIANGLE operation could address these shortcomings of conventional PD as indicated in several retrospective studies. However, this technique could be associated with more adverse events for patients including intractable diarrhoea. The TRIANGLE trial will close the evidence gap as well as offer a risk-benefit assessment of this more radical approach to PD. TRIAL REGISTRATION: German Clinical Trials Register DRKS00030576 (UTN U1111-1243-4412) 19th December 2022.

The correlation of age and extension length in DeBakey type I aortic dissection: are older patients over 70 years at a lower risk?

OBJECTIVES: Age-related atherosclerosis has been shown to cause aortic stiffness and wall rigidification. This analysis aimed to correlate age and dissection extension length in a large contemporary multicentre study. We hypothesize that younger patients suffer more extensive DeBakey type I dissection due to aortic wall integrity, allowing unhindered extension within the layers. METHODS: The perioperative data of 3385 patients from the German Registry for Acute Aortic Dissection Type A were retrospectively analyzed with regard to postoperative outcomes and dissection extension. Patients with DeBakey type I aortic dissection (n = 2510) were retrospectively identified and divided into 2 age groups for comparison: ≤69 years (n = 1741) and ≥70 years (n = 769). Patients with DeBakey type II dissection or connective tissue disease were excluded from the analysis. RESULTS: In younger patients (≤69 years), aortic dissection involved the supra-aortic vessels significantly more often (52.0% vs 40.1%; P < 0.001) and extended significantly further downstream the aorta: descending aorta (68.4% vs 57.1%; P < 0.001), abdominal aorta (54.6% vs 42.1%; P < 0.001) and iliac bifurcation (36.6% vs 26.0%; P < 0.001). Consequently, younger patients also presented with significantly higher incidences of preoperative cerebral (P < 0.001), spinal (P < 0.001), visceral (P < 0.001), renal (P = 0.013) and peripheral (P < 0.001) malperfusion. In older patients (≥70 years), dissection extent was significantly more often limited to the level of the aortic arch (40.9% vs 29.2%; P < 0.001). No significant difference was found with regard to 30-day mortality (20.7% vs 23.6%; P = 0.114). CONCLUSIONS: Extensive DeBakey type I aortic dissection is less frequent in older patients ≥70 years than in younger patients. In contrast, younger patients suffer more often from preoperative organ malperfusion and associated complications. Postoperative mortality remains high irrespective of age groups.

Distal Pancreatectomy With En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer: A Safe and Effective Procedure.

OBJECTIVE: To determine perioperative and oncologic outcomes after distal pancreatectomy with en bloc resection of the celiac axis (DP-CAR). BACKGROUND: DP-CAR can be used in a selective group of patients to resect locally advanced pancreatic cancer involving the celiac axis or common hepatic artery without arterial reconstruction by preserving retrograde blood flow via the gastroduodenal artery to the liver and stomach. METHODS: We analyzed all consecutive patients who had undergone DP-CAR between May 2003 and April 2022 at a tertiary hospital specialized in pancreatic surgery and present one of the largest single-center studies. RESULTS: A total of 71 patients underwent DP-CAR. Additional venous resection (VR) of the mesenterico-portal axis was performed in 31 patients (44%) and multivisceral resection (MVR) in 42 patients (59%). Margin-free (R0) resection was achieved in 40 patients (56%). The overall 90-day mortality rate was 8.4% for the entire patient cohort. After a cumulated experience of 16 cases, the 90-day mortality dropped to 3.6% in the following 55 patients. Extended procedures with (+) additional MVR with or without (+/-) VR resulted in higher major morbidity (Clavien-Dindo ≥IIIB; standard DP-CAR: 19%; DP-CAR + MVR +/- VR: 36%) and higher 90-day mortality (standard DP-CAR: 0%; DP-CAR + MVR +/- VR: 11%). Median overall survival after DP-CAR was 28 months. CONCLUSIONS: DP-CAR is a safe and effective procedure but requires experience. Frequently, surgical resection has to be extended with MVR and VR to accomplish tumor resection, which results in promising oncologic outcomes. However, extended resections were associated with increased morbidity and mortality.

Overall morbidity after total minimally invasive keyhole oesophagectomy versus hybrid oesophagectomy (the MICkey trial): study protocol for a multicentre randomized controlled trial.

BACKGROUND: Oesophageal cancer (EC) is the sixth leading cause of cancer death worldwide. Oesophageal resection is the only curative treatment option for EC which is frequently performed via an abdominal and right thoracic approach (Ivor-Lewis operation). This 2-cavity operation is associated with a high risk of major complications. To reduce postoperative morbidity, several minimally invasive techniques have been developed that can be broadly classified into either hybrid oesophagectomy (HYBRID-E) via laparoscopic/robotic abdominal and open thoracic surgery or total minimally invasive oesophagectomy (MIN-E). Both, HYBIRD-E and MIN-E, compare favourable to open oesophagectomy. However, there is still an evidence gap comparing HYBRID-E with MIN-E with regard to postoperative morbidity. METHODS: The MICkey trial is a multicentre randomized controlled superiority trial with two parallel study groups. A total of 152 patients with oesophageal cancer scheduled for elective oesophagectomy will be randomly assigned 1:1 to the control group (HYBRID-E) or to the intervention group (MIN-E). The primary endpoint will be overall postoperative morbidity assessed via the comprehensive complication index (CCI) within 30 days after surgery. Specific perioperative parameters, as well as patient-reported and oncological outcomes, will be analysed as secondary outcomes. DISCUSSION: The MICkey trial will address the yet unanswered question whether the total minimally invasive oesophagectomy (MIN-E) is superior to the HYBRID-E procedure regarding overall postoperative morbidity. TRIAL REGISTRATION: DRKS00027927 U1111-1277-0214. Registered on 4th July 2022.

Impact of age on indication for chemotherapy in early breast cancer patients: results from 104 German institutions from 2008 to 2017.

PURPOSE: Today, the decision to treat patients with chemotherapy for early breast cancer (EBC) is made based on the patient's individual risk stratification and tumor biology. In cases with chemotherapy indication, the neoadjuvant application (NACT) is the preferred option in comparison with primary surgery and adjuvant chemotherapy (ACT). Age remains a relevant factor in the decision-making process. The aim of the present study was to illustrate the impact of age on the use of systemic therapy in clinical routine. METHODS: The study separately analyzed chemotherapy use among six age cohorts of EBC patients who had been treated at 104 German breast units between January 2008 and December 2017. RESULTS: In total, 124,084 patients were included, 46,279 (37.3%) of whom had received chemotherapy. For 44,765 of these cases, detailed information on treatment was available. Within this cohort, chemotherapy was administered as NACT to 14,783 patients (33.0%) and as ACT to 29,982 (67.0%) patients. Due to the higher prevalence of unfavorable tumor subtypes, younger patients had a higher rate of chemotherapy (≤ 29y: 74.2%; 30-39y: 71.3%) and a higher proportion of NACT administration ( ≤ 29y: 66.9%; 30-39y: 56.0%) in comparison with elderly patients, who had lower rates for overall chemotherapy (60-69y: 37.5%; ≥ 70y: 17.6%) and NACT (60-69y: 25.5%; ≥ 70y: 22.8%). Pathologic complete response was higher in younger than in older patients (≤ 29y: 30.4% vs. ≥ 70y: 16.7%), especially for HER2- subtypes. CONCLUSION: The data from the nationwide German cohort reveal relevant age-dependent discrepancies concerning the use of chemotherapy for EBC.

Completion Pancreatectomy After Pancreatoduodenectomy: Who Needs It?

OBJECTIVE: The objective of this study was to identify the indications for and report the outcomes of completion pancreatectomy (CPLP) in the postoperative course after pancreatoduodenectomy (PD). BACKGROUND: CPLP may be considered or even inevitable for damage control after PD. METHODS: A prospectively maintained database of all patients undergoing PD between 2001 and 2019 was searched for patients who underwent CPLP in the postoperative course after PD. Baseline characteristics, perioperative details, and outcomes of CPLP patients were analyzed and specific indications for CPLP were identified. RESULTS: A total of 3953 consecutive patients underwent PD during the observation period. CPLP was performed in 120 patients (3%) after a median of 10 days following PD. The main indications for CPLP included postpancreatectomy acute necrotizing pancreatitis [n=47 (39%)] and postoperative pancreatic fistula complicated by hemorrhage [n=41 (34%)] or associated with uncontrollable leakage of the pancreatoenteric anastomosis [n=23 (19%)]. The overall 90-day mortality rate of all 3953 patients was 3.5% and 37% for patients undergoing CPLP. CONCLUSIONS: Our finding that only very few patients (3%) need CPLP suggests that conservative, interventional, and organ-preserving surgical measures are the mainstay of complication management after PD. Postpancreatectomy acute necrotizing pancreatitis, uncontrollable postoperative pancreatic fistula, and fistula-associated hemorrhage are highly dangerous and represent the main indications for CPLP after PD.

Pancreatic Surgery in Children: Complex, Safe and Effective.

OBJECTIVE: The aim of this study is to assess indications for and report outcomes of pancreatic surgery in pediatric patients. BACKGROUND: Indications for pancreatic surgery in children are rare and data on surgical outcomes after pediatric pancreatic surgery are scarce. METHODS: All children who underwent pancreatic surgery at a tertiary hospital specializing in pancreatic surgery between 2003 and 2022 were identified from a prospectively maintained database. Indications, surgical procedures, and perioperative as well as long-term outcomes were analyzed. RESULTS: In total, 73 children with a mean age of 12.8 years (range: 4 months-18 years) underwent pancreatic surgery during the observation period. Indications included chronic pancreatitis (n=35), pancreatic tumors (n=27), and pancreatic trauma (n=11). Distal pancreatectomy was the most frequently performed procedure (n=23), followed by pancreatoduodenectomy (n=19), duodenum-preserving pancreatic head resection (n=10), segmental pancreatic resection (n=7), total pancreatectomy (n=3), and others (n=11). Postoperative morbidity occurred in 25 patients (34.2%), including 7 cases (9.6%) with major complications (Clavien-Dindo≥III). There was no postoperative (90-day) mortality. The 5-year overall survival was 90.5%. The 5-year event-free survival of patients with chronic pancreatitis was 85.7%, and 69.0% for patients with pancreatic tumors. CONCLUSION: This is the largest single-center study on pediatric pancreatic surgery in a Western population. Pediatric pancreatic surgery can be performed safely. Centralization in pancreatic centers with high expertise in surgery of adult and pediatric patients is important as it both affords the benefits of pancreatic surgery experience and ensures that surgical management is adapted to the specific needs of children.

Correction: Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

[This corrects the article DOI: 10.1055/a-2196-6224.].

Perioperative prothrombin complex concentrate and fibrinogen administration are associated with thrombotic complications after liver transplant.

Background: Use of intraoperative prothrombin complex concentrates (PCC) and fibrinogen concentrate administration has been linked to thrombotic events. However, it is unknown if its use is associated with thrombotic events after liver transplant. Methods and analysis: We conducted a post hoc analysis of a prospectively conducted registry database study on patients who underwent liver transplant between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariate and multivariate analyses were used to determine the association between PCC and fibrinogen concentrate administration and thrombotic complications. Results: Data from 939 transplantations were included in the analysis. Perioperative PCC or fibrinogen administration was independently associated with the primary composite endpoint Hepatic artery thrombosis (HAT), Portal vein thrombosis (PVT), and inferior vena cava thrombosis [adjusted HR: 2.018 (1.174; 3.468), p = 0.011]. PCC or fibrinogen administration was associated with the secondary endpoints 30-day mortality (OR 4.225, p < 0.001), graft failure (OR 3.093, p < 0.001), intraoperative blood loss, red blood cell concentrate, fresh frozen plasma and platelet transfusion, longer hospitalization, and longer length of stay in intensive care units (ICUs) (all p < 0.001). PCC or fibrinogen administration were not associated with pulmonary embolism, myocardial infarction, stroke, or deep vein thrombosis within 30 days after surgery. Conclusion: A critical review of established strategies in coagulation management during liver transplantation is warranted. Perioperative caregivers should exercise caution when administering coagulation factor concentrate during liver transplant surgery. Prospective randomized controlled trials are needed to establish causality for the relationship between coagulation factors and thrombotic events in liver transplantation. Further studies should be tailored to identify patient subgroups that will likely benefit from PCC or fibrinogen administration.