Short- and long-term effects of imatinib in hospitalised COVID-19 patients: A randomised trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

Impact of hospital volume on failure to rescue for complications requiring reoperation after elective colorectal surgery: multicentre propensity score-matched cohort study.

BACKGROUND: It has previously been reported that there are similar reoperation rates after elective colorectal surgery but higher failure-to-rescue (FTR) rates in low-volume hospitals (LVHs) versus high-volume hospitals (HVHs). This study assessed the effect of hospital volume on reoperation rate and FTR after reoperation following elective colorectal surgery in a matched cohort. METHODS: Population-based retrospective multicentre cohort study of adult patients undergoing reoperation for a complication after an elective, non-centralized colorectal operation between 2006 and 2017 in 11 hospitals. Hospitals were divided into either HVHs (3 hospitals, median ≥126 resections per year) or LVHs (8 hospitals, <126 resections per year). Patients were propensity score-matched (PSM) for baseline characteristics as well as indication and type of elective surgery. Primary outcome was FTR. RESULTS: A total of 6428 and 3020 elective colorectal resections were carried out in HVHs and LVHs, of which 217 (3.4%) and 165 (5.5%) underwent reoperation (P < 0.001), respectively. After PSM, 142 patients undergoing reoperation remained in both HVH and LVH groups for final analyses. FTR rate was 7.7% in HVHs and 10.6% in LVHs (P = 0.410). The median Comprehensive Complication Index was 21.8 in HVHs and 29.6 in LVHs (P = 0.045). There was no difference in median ICU-free days, length of stay, the risk for permanent ostomy or overall survival between the groups. CONCLUSION: The reoperation rate and postoperative complication burden was higher in LVHs with no significant difference in FTR compared with HVHs.

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Comparison of Oncological and Surgical Outcomes Between Formal Pancreatic Resections and Parenchyma-Sparing Resections for Small PanNETs (<2 cm): Pancreas2000 Research and Educational Program (Course 9) Study Protocol.

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors but incidence is increasing. An increasing number of these tumors are diagnosed incidentally when they are small (<2 cm) and when patients are asymptomatic. The European Neuroendocrine Tumor Society (ENETS) recommends conservative watch and wait policy for these patients. However, best surgical approach (parenchyma-sparing or formal oncological resection) for these small tumors when surgery is indicated is currently unknown. Parenchyma-sparing resections such as enucleation is associated with higher risk of post-operative morbidity compared to formal oncological resections. They are also be associated with potentially inadequate surgical margin clearance and with lack of lymphadenectomy for full pathological staging. Method: This study is a retrospective study and the aim is to analyze pre-operative clinical predictors of nodal metastases for small PanNETs to identify which patients are at a lower risk of lymph node metastases and are therefore suitable for parenchyma-sparing resection. Conclusion: The primary endpoint of this study is to determine if pre-operative clinical predictors such as tumor size are associated with lymph node involvement in small PanNETs.

INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn (INCARO): a multicentre, open-label, randomised controlled trial - study protocol.

INTRODUCTION: CT is the primary imaging option for acute abdominal pain in adults. Intravenous (IV) contrast media use improves CT quality but may cause post-contrast acute kidney injury (PC-AKI). Retrospective studies show no association between reduced baseline renal function and IV contrast CT, but, to our knowledge, no data from randomised controlled trials exist. METHODS AND ANALYSIS: The INCARO (INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn) trial is a multicentre, open-label, parallel group, superiority, individually randomised controlled trial comparing IV contrast-enhanced CT to native CT in patients requiring emergency abdominal or body CT with impaired renal function defined as an estimated glomerular filtration rate (eGFR) of 15 to 45 mL/min/1.73 m2. The primary outcome is a composite of all-cause mortality or renal replacement therapy (RRT) within 90 days from CT. Secondary outcomes are AKI measured by KDIGO (The Kidney Disease: Improving Global Outcomes) criteria within 72 hours from CT, organ dysfunction defined by mSOFA (modified Sequential Organ Failure Assessment) criteria after 48 hours from CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment. All-cause mortality, need for RRT and renal transplant in long-term follow-up are also measured. The calculated sample size is 994 patients. Patient recruitment is estimated to take 3 years. ETHICS AND DISSEMINATION: The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: NCT04196244.

Role of Pre-operative Inflammatory Markers as Predictors of Lymph Node Positivity and Disease Recurrence in Well-Differentiated Pancreatic Neuroendocrine Tumours: Pancreas2000 Research and Educational Program (Course 9).

Pancreatic neuroendocrine tumours (PNET) is a rare disease and in the absence of metastases, surgical resection is recommended. Key factors affecting survival in PNETs are the stage and grade of the disease, but there is increasing evidence suggesting lymph node involvement is associated with shorter disease-free and overall survival. Ability to predict the likelihood of lymph node involvement at the time of diagnosis would affect surgical decision making in these patients. A systemic inflammatory index such as neutrophil to lymphocyte ratio or platelet to lymphocyte ratio has been associated with poor prognosis in several cancers. Method: This study is a retrospective multi-centre study. The data including pre-operative inflammatory markers such as haemoglobin, neutrophil, lymphocyte counts and pathological data including number of positive lymph nodes, tumour grade and size, are collected to assess the association between inflammatory index and lymph node involvement. Conclusion: This study aims to assess the value of routinely available pre-operative haematological markers in predicting lymph node involvement in non-functioning PNETs.

Transcatheter arterial embolization in hepatic tumor hemorrhage.

Objective: Spontaneous hepatic tumor hemorrhage is a rare but challenging emergency especially among cirrhotic patients with poor hepatic function. This study aimed at analyzing the safety, efficacy and feasibility of transcatheter arterial embolization (TAE) in the treatment of hepatic tumor hemorrhage. Methods: This retrospective study included all patients undergoing embolization attempt for hepatic tumor hemorrhage in the Helsinki University Hospital during 2004-2017. Electronic medical records provided the study data. Outcomes included the 30-day rebleeding, complication and mortality rates, need for blood transfusions, durations of intensive care unit and hospital admissions, estimates of overall survival, and analysis of factors associated with 30-day mortality. Results: During the study period, 49 patients underwent angiography for hepatic tumor hemorrhage. TAE was technically feasible in 45 patients (92%), and controlled the bleeding with the first attempt in 84%. The 30-day complication and mortality rates were 57 and 33%, respectively. Major complications occurred in 33% of patients. In-hospital mortality was higher among cirrhotic than non-cirrhotic patients (55 versus 7%, p < .001). Patients with bleeding hepatic metastases, but no cirrhosis, had an in-hospital mortality of 0% with no major complications. Patients with benign etiology had a good prognosis and no bleeding- or tumor-related mortality. Discussion: TAE is an effective method in controlling the bleeding in spontaneous hepatic hemorrhage. Underlying pathology determines the prognosis that is poor especially in cirrhotic patients with bleeding hepatocellular carcinoma.

Transcatheter Arterial Embolization in Lower Gastrointestinal Bleeding: Ischemia Remains a Concern Even with a Superselective Approach.

PURPOSE: To evaluate the safety, efficacy, and feasibility of transcatheter arterial embolization (TAE) in the treatment of lower gastrointestinal bleeding (LGIB). METHODS: Study group comprised all patients receiving angiography for LGIB in the Helsinki University Hospital during the period of 2004-2016. Hospital medical records provided the study data. Rebleeding, complication, and mortality rates (≤ 30 days) were the primary outcomes. Secondary outcomes included need for blood transfusions, durations of intensive care unit and hospital admissions, incidence of delayed rebleeding, and long-term complications, as well as overall survival. RESULTS: During the study period, angiography for LGIB was necessary on 123 patients. Out of 123, 55 (45%) underwent embolization attempts. TAE was technically successful in 53 (96%). Rebleeding occurred in 14 (26%). The complication rate was 36%, minor complications occurring in 10 (19%) and major in nine (17%). Major complications resulted in bowel resection in seven (13%). Post embolization ischemia was the most common single complication seen in nine (17%). The mortality rate was 6%. Survival estimates of 1 and 5 years were 79 and 49%. DISCUSSION: LGIB is a severe physiological insult occurring in patients who are often elderly and moribund. Although major post embolization complications occur, transcatheter arterial embolization should be the first-line approach over surgery in profuse LGIB in patients with hemodynamic instability, when colonoscopy fails or is unavailable, or when computerized tomography angiography detects small intestinal bleeding.

Bleeding gastric and duodenal ulcers: case-control study comparing angioembolization and surgery.

OBJECTIVES: To compare the safety, efficacy and feasibility of transcatheter arterial embolization (TAE) and surgery in the treatment of bleeding gastric and duodenal ulcers (BGDUs). MATERIALS AND METHODS: The study group comprised patients receiving TAE or surgery for BGDUs after failed endoscopic hemostasis in Helsinki University Hospital (HUH) during 2000-2015. Hospital medical records provided study data. 30-d mortality and rebleeding rates were the primary outcomes. Postoperative complications, blood transfusion rate, and the durations of intensive care and hospital admissions were the secondary outcomes. RESULTS: During the study period, BGDUs lead to 1583 hospital admissions. TAE or surgery was necessary on 85 (5.4%) patients, 43 receiving surgery and 42 TAE. Out of 42, 16 received prophylactic TAE. Two underwent angiography and TAE to localize the bleeding. The remaining 24 received TAE for active or recurrent bleeding after endoscopy. The comparison of TAE (n = 24) and surgery (n = 43) included only patients with active or recurrent bleeding. Mortality rate was 12.5% after TAE and 25.6% after surgery (p = 0.347). Rebleeding rate was 25% after TAE and 16.3% after surgery (p = 0.641). Postprocedural complications were less frequent after TAE than surgery (37.5 vs. 67.4%, p = 0.018). Other secondary outcomes did not differ. Out of 85 procedures, 14 (16.5%) took place between midnight and 8 a.m., all nighttime interventions being surgeries. CONCLUSIONS: Mortality and rebleeding rates did not differ between TAE and surgery. With less postoperative complications, TAE should be the preferred hemostatic method when endoscopy fails.

Bleeding pancreatic pseudoaneurysms: management by angioembolization combined with therapeutic endoscopy.

BACKGROUND: Bleeding pancreatic pseudocysts (PPCs) are a rare but lethal complication of pancreatitis. Transcatheter arterial embolization (TAE) is the first-line treatment of acute hemorrhage, but consensus on the definitive management of bleeding PPCs is lacking. The aim of this study was to evaluate the safety and efficacy of the combination of TAE and therapeutic endoscopy in the treatment of bleeding PPCs. METHODS: Patients with acute or chronic pancreatitis treated for bleeding PPCs in Helsinki University Hospital during 2004-2014 comprised the study group. Inpatients with acute necrotizing pancreatitis were excluded. Patients underwent TAE as the primary treatment to control the bleeding. Therapeutic endoscopy performed on an outpatient visit after TAE allowed the definitive treatment of PPCs. RESULTS: A total of 58 patients underwent TAE. Re-bleeding rate (<30 days) was 15.5 %, necessitating re-embolization on seven and surgical intervention on two patients. Overall, TAE success rate was 96.6 %. Mortality rate (<30 days) was 3.4 %. Of the 58, 47 patients were followed up for their PPCs in our unit. PPCs resolved spontaneously in 13 (27.1 %). The remaining 34 had an endoscopic treatment attempt with endoscopic draining performed on 32 and unsuccessful cannulation on two (5.9 %). Of the 32 patients with initially successful endoscopy, 7 (21.9 %) needed an additional drainage procedure (six non-surgical and one surgical). Overall success rate of non-surgical management was 91.5 %. Post-endoscopy mortality rate (<30 days) was 2.9 %. Our follow-up continued for 15 (1-75) months. By the time of data retrieval, 35 of 58 patients had died with alcohol liver disease being the most common cause of death. Five-year survival estimate was 63 %. CONCLUSIONS: Bleeding pancreatic pseudoaneurysms require non-surgical management. We need more data on the optimal timing of therapeutic endoscopy and on the role of empirical embolizations.