[Acute thoracoabdominal aortic dissection]. / Acute dissectie van de thoraco-abdominale aorta.

BACKGROUND: A thoracic aortic dissection is a rare condition (2.5-3.5 per 100,000 person years) and patients can present with atypical symptoms. However, a missed diagnosis is often fatal. CASE DESCRIPTION: A 66-years-old male presents himself at the GP's office with sharp pain and loss of strength and sensation in the right arm. Pulse and blood pressure are undetectable on the right arm. An immediate thoracoabdominal CT-angiography is ordered in the nearest hospital. It reveals an aortic dissection (Stanford type A) and the patient is swiftly transferred to a tertiary referral hospital. Upon emergency surgery, the aortic valve, -root and ascending aorta are replaced. The patient is discharged home after one month. CONCLUSION: Swift recognition and referral are paramount to survival in aortic dissection. Patients with a low suspicion can be referred to the closed hospital for immediate imaging. When suspicion is high, direct transfer to a thoracic surgery hospital is warranted.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Oncogenic KRAS sensitises colorectal tumour cells to chemotherapy by p53-dependent induction of Noxa.

BACKGROUND: Oxaliplatin and 5-fluorouracil (5-FU) currently form the backbone of conservative treatment in patients with metastatic colorectal cancer. Tumour responses to these agents are highly variable, but the underlying mechanisms are poorly understood. Our previous results have indicated that oncogenic KRAS in colorectal tumour cells sensitises these cells to chemotherapy. METHODS: FACS analysis was used to determine cell-cycle distribution and the percentage of apoptotic and mitotic cells. A multiplexed RT-PCR assay was used to identify KRAS-controlled apoptosis regulators after exposure to 5-FU or oxaliplatin. Lentiviral expression of short-hairpin RNAs was used to suppress p53 or Noxa. RESULTS: Oncogenic KRAS sensitised colorectal tumour cells to oxaliplatin and 5-FU in a p53-dependent manner and promoted p53 phosphorylation at Ser37 and Ser392, without affecting p53 stabilisation, p21 induction, or cell-cycle arrest. Chemotherapy-induced expression of the p53 target gene Noxa was selectively enhanced by oncogenic KRAS. Suppression of Noxa did not affect p21 induction or cell-cycle arrest, but reduced KRAS/p53-dependent apoptosis after exposure to chemotherapy in vitro and in tumour xenografts. Noxa suppression did not affect tumour growth per se, but strongly reduced the response of these tumours to chemotherapy. CONCLUSION: Oncogenic KRAS determines the cellular response to p53 activation by oxaliplatin or 5-FU, by facilitating apoptosis induction through Noxa.

Surgical intervention in patients with necrotizing pancreatitis.

BACKGROUND: This study evaluated the various surgical strategies for treatment of (suspected) infected necrotizing pancreatitis (INP) and patient referrals for this condition in the Netherlands. METHODS: This retrospective study included all 106 consecutive patients who had surgical treatment for INP in the period 2000-2003 in one of eight Dutch university medical centres including three teaching hospitals. Surgical approaches included an open abdomen strategy, laparotomy with continuous postoperative lavage, minimally invasive procedures or laparotomy with primary abdominal closure. The National Hospital Registration System was searched to identify patients with acute pancreatitis who were admitted to the 90 Dutch hospitals that did not participate in the present study. RESULTS: The overall mortality rate was 34.0 per cent, 70 per cent (16 of 23) for the open abdomen strategy, 25 per cent (13 of 53) for continuous peritoneal lavage, 11 per cent (two of 18) for minimally invasive procedures and 42 per cent (five of 12) for primary abdominal closure (P < 0.001). During the study interval, 44 (12.2 per cent) of 362 patients with acute pancreatitis who were likely to require surgical intervention had been referred to university medical centres. CONCLUSION: Laparotomy with continuous postoperative lavage is the surgical strategy most often used in the Netherlands. The results of the open abdomen strategy are poor whereas a minimally invasive approach seems promising.