The role of surgery in the treatment of oligoprogression after systemic treatment for advanced non-small cell lung cancer.

OBJECTIVES: Patients with advanced stage non-small cell lung cancer (NSCLC) are generally considered incurable. The mainstay of treatment for these patients is systemic therapy. The addition of local treatment, including surgery, remains controversial. Oligoprogression is defined as advanced stage NSCLC with limited progression of disease after a period of prolonged disease stabilisation or after a partial or complete response on systemic therapy. In this retrospective study we evaluated outcome and survival of patients who underwent a resection for oligoprogression after systemic therapy for advanced stage NSCLC. MATERIALS AND METHODS: Patients with oligoprogression after systemic treatment for advanced NSCLC who were operated in the Antoni van Leeuwenhoek Hospital were included. Patient and treatment characteristics were collected in relation to progression free survival (PFS) and overall survival (OS). RESULTS: Between January 2015 and December 2019, 28 patients underwent surgery for an oligoprogressive lesion (primary tumor lung (n = 12), other metastatic site (n = 16)). Median age at time of resection was 60 years (39-86) and 57% were female. Postoperative complications were observed in 2 patients (7%). Progression of disease after resection of the oligoprogressive site was observed in 17 patients (61%). Median PFS was 7 months since date of resection (95% CI 6.0-25.0) and median OS was not reached. Seven patients (25%) died during follow-up. Age was predictive for OS and clinical T4 stage was predictive for PFS. M1 disease at initial presentation was predictive for better PFS compared to patients who were diagnosed with M0 disease initially. Patients who underwent resection because of oligoprogression of the primary lung tumour had a better PFS, when compared to oligoprogression of another metastastic site. CONCLUSION: Surgical resection of an oligoprogressive lesion in patients with advanced NSCLC treated with systemic treatment is feasible and might be considered in order to achieve long term survival.

A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination.

BACKGROUND: Circulatory collapse is a leading cause of mortality among traumatic major exsanguination and in ruptured aortic aneurysm patients. Approximately 40% of patients die before hemorrhage control is achieved. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive surgical or endovascular repair. A systematic review was conducted for the current clinical use of REBOA in patients with hemodynamic instability and to discuss its potential role in improving prehospital and in-hospital outcome. METHODS: Systematic review and meta-analysis (1900-2017) using MEDLINE, Cochrane, EMBASE, Web of Science and Central and Emcare using the keywords "aortic balloon occlusion", "aortic balloon tamponade", "REBOA", and "Resuscitative Endovascular Balloon Occlusion" in combination with hemorrhage control, hemorrhage, resuscitation, shock, ruptured abdominal or thoracic aorta, endovascular repair, and open repair. Original published studies on human subjects were considered. RESULTS: A total of 490 studies were identified; 89 met criteria for inclusion. Of the 1436 patients, overall reported mortality was 49.2% (613/1246) with significant differences (p < 0.001) between clinical indications. Hemodynamic shock was evident in 79.3%, values between clinical indications showed significant difference (p < 0.001). REBOA was favored as treatment in trauma patients in terms of mortality. Pooled analysis demonstrated an increase in mean systolic pressure by almost 50 mmHg following REBOA use. CONCLUSION: REBOA has been used in trauma patients and ruptured aortic aneurysm patients with improvement of hemodynamic parameters and outcomes for several decades. Formal, prospective study is warranted to clarify the role of this adjunct in all hemodynamic unstable patients.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology.

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.

[A man with abdominal pain and subsequently a periumbilical haematoma]. / Een man met buikpijn en daarna een navelhematoom.

A 71-year-old male presented with periumbilical ecchymosis formed after acute onset of abdominal pain and near collapse. At the time of presentation the haematoma was the only symptom. Following a CT scan, the diagnosis of a contained rupture of an iliac artery aneurysm was made. The patient was successfully treated with an endovascular stent graft.

The role of initial clinical presentation, comorbidity and treatment in multiple myeloma patients on survival: a detailed population-based cohort study.

PURPOSE: This prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. METHODS: Detailed clinical information was obtained from the population-based registry 'HemoBase' during the period January 2005 to January 2013, with a follow-up to January 2014. RESULTS: Overall, the symptomatic MM patients (n = 225) had a median OS of 40 months. In the age categories <65, 65-75 and ≥75 years, 99, 94 and 87% of the patients received treatment, with a median OS of 92, 42 and 31 months, respectively. OS for patients with or without treatment was 43 and 3 months, respectively. In multivariable analysis, risk factors for worse OS were increasing age (<65: reference; 65-75: HRadj. = 2.2 (95% CI 1.3-3.7) and ≥75: HRadj. = 2.8 (95% CI 1.7-4.8); P < 0.001), not receiving initial treatment (HRadj. = 4.0 (95% CI 2.1-7.7); P < 0.001), hypercalcaemia (P < 0.001, HRadj. = 1.7 (95% CI 1.2-2.6), P = 0.006) and impaired renal function (HRadj. = 2.6 (95% CI 1.7-4.0); P < 0.001). CONCLUSIONS: Increasing age, not receiving initial treatment, hypercalcaemia and impaired renal function at initial presentation were independent risk factors for worse OS. Comorbidity according to Charlson comorbidity index score was not an independent variable predicting OS.

A Peculiar Case of a Floating Angio-Seal.

PURPOSE: To show a complication of the use of an Angio-Seal™ closure device. CASE: We present a patient with a systolic murmur in his femoral artery after PCI. The murmur was caused by a dislocated Angio-Seal™, a vascular closure device. This was diagnosed by Doppler Ultrasound. The device was surgically removed. CONCLUSION: Vascular complications, such as lower limb ischemia, requiring surgical intervention tend to be higher after use of a vascular closure device. We advise routine physical examination of the puncture site after percutaneous closure with a vascular closure device, such as an Angio-Seal™. The removal of the device can be performed via an open or endoscopic approach, based on available experience.

A Pseudoaneurysm of the Deep Palmar Arch After Penetrating Trauma to the Hand: Successful Exclusion by Ultrasound Guided Percutaneous Thrombin Injection.

INTRODUCTION: Pseudoaneurysm of the hand is a rare condition; most are treated surgically. Ultrasound guided thrombin injection has not previously been reported as a treatment option for pseudoaneurysms of the deep palmar arch. REPORT: A man was referred to the emergency department with a swollen, painful hand after penetrating trauma. On physical examination, a pulsating tumor was found on the dorsum of the hand. Imaging revealed a pseudoaneurysm vascularized by the deep palmar arch. Ultrasound guided percutaneous thrombin injection was successfully performed. CONCLUSION: Thrombin injection might be a safe alternative option in the treatment of pseudoaneurysm of the deep palmar arch.

Systematic review of patient-reported outcome measures in the surgical treatment of patients with esophageal cancer.

Esophageal cancer is currently the eighth most common cancer worldwide. Improvements in operative techniques and neoadjuvant therapies have led to improved outcomes. Resection of the esophagus carries a high risk of severe complications and has a negative impact on health-related quality of life (QOL). The aim of this study was to assess which patient-reported outcome measures (PROMs) are used to measure QOL after esophagectomy for cancer. A comprehensive search of original articles was conducted investigating QOL after surgery for esophageal carcinoma. Two authors independently selected relevant articles, conducted clinical appraisal, and extracted data (PJ and JS). Out of 5893 articles, 58 studies were included, consisting of 41 prospective and 17 retrospective cohort studies, including a total of 6964 patients. These studies included 11 different PROMs. The existing PROMs could be divided into generic, symptom-specific, and disease-specific questionnaires. The European Organisation for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ C-30) along with the EORTC QLQ-OESophagus module OES18 was the most widely used; in 42 and 32 studies, respectively. The EORTC and the Functional Assessment of Cancer Therapy (FACT) questionnaires use an oncological module and an organ-specific module. One validation study was available, which compared the FACT and EORTC, showing moderate to poor correlation between the questionnaires. A great variety of PROMs are being used in the measurement of QOL after surgery for esophageal cancer. A questionnaire with a general module along with a disease-specific module for assessment of QOL of different treatment modalities seem to be the most desirable, such as the EORTC and the FACT with their specific modules (EORTC QLQ-OES18 and FACT-E). Both are developed in different treatment modalities, such as in surgical patients. With regard to reproducibility of current results, the EORTC is recommended.

Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study.

PURPOSE: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. METHODS: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment ("watch and wait"), chlorambucil treatment only, and patients with other treatment(s). RESULTS: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. CONCLUSIONS: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment.

Real-world costs of chronic lymphocytic leukaemia in the Netherlands.

We performed a comprehensive cost calculation identifying the main cost drivers of treatment of chronic lymphocytic leukaemia in daily practice. In our observational study 160 patient charts were reviewed repeatedly to assess the treatment strategies from diagnosis till the study end. Ninety-seven patients (61%) received ≥1 treatment lines during an average follow-up time of 6.4 years. The average total costs per patient were €41,417 (€539 per month). The costs varied considerably between treatment groups and between treatment lines. Although patients were treated with expensive chemo(immuno-)therapy, the main cost driver was inpatient days for other reasons than administration of chemo(immuno-)therapy.

Infections of intravascular bare metal stents: a case report and review of literature.

OBJECTIVE: The objective of the paper is to present a case of an infected bare metal stent in the left common iliac artery that was removed by an urgent operation, and to review the literature on diagnosis and outcome of infected coronary and non-coronary metal stents. METHODS: A systematic search of the Medline database was performed with the purpose of identifying risk factors, signs and symptoms, imaging strategies, and treatment modalities of bare metal stent infections, both coronary and peripheral. RESULTS: In total, 76 additional studies/case reports (48 non-coronary; 29 coronary) were included and analyzed. Intravascular bare metal stent infections are a rare but serious complication, often leading to emergency surgery (overall: 75.3%; non-coronary cases: 83.3%; coronary cases: 62.1%). In 25.0% of the non-coronary cases, infection led to amputation of an extremity or removal of viscera. Reported mortality was up to 32.5% of the cases (non-coronary: 22.9%; coronary 48.3%). Physicians should always be suspicious of a stent infection when patients present with aspecific symptoms such as fever and chills after stent placement. Additional imaging can be used to detect the presence of a pseudoaneurysm. A PET-CT is an ideal medium for identification of a stent infection. CONCLUSIONS: Intravascular stent infection is associated with a high risk of morbidity and mortality. Surgery is the preferred treatment option, but not always possible, especially in patients with a coronary stent. In selected cases, bare metal stent infections may be prevented by the use of prophylactic antibiotics at stent placement.

Infection of endovascular abdominal aortic aneurysm stent graft after urosepsis: case report and review of the literature.

Infection of endovascular abdominal aneurysm stent grafts is an uncommon but known complication. Inoculation with bacteria of the endovascular abdominal aneurysm stent graft during the actual implantation, in the periprocedural hospitalization or later due to an aortoenteric fistula, has been described in the literature. We report a case of endovascular abdominal aortic aneurysm stent graft infection occurring 40 months after implantation in a patient doing well up to an episode of urosepsis. In conclusion, we postulate that poor intraluminal healing of stent grafts, as observed in several explant studies, may result in a higher susceptibility to episodes of bacteremia than prosthetic vascular grafts inserted during open repair. We therefore consider the administration of prophylactic antibiotics in patients with endovascular stent grafts during periods with a likelihood of bacteremia.

A case of intrathoracic stomach and spleen after aortic repair: an unusual complication.

UNLABELLED: A patient is described who presented with an intrathoracic stomach and spleen two weeks after aortic repair for an aortoduodenal fistula. At an urgent laparotomy the stomach was repositioned and the spleen removed. The patient recovered fully. The possible mechanism of this severe complication is discussed and relevant literature reviewed. KEYWORDS: Aortoduodenal fistula; Complication; Intrathoracic stomach; Intrathoracic spleen.

Implementation of endovenous laser ablation for varicose veins in a large community hospital: the first 400 procedures.

UNLABELLED: Endovenous laser ablation (ELA) has become a standard treatment of the incompetent great saphenous vein (GSV). Our prospective audit examines the implementation of this new method in a large community hospital with special attention to obstacles, technical results, pain scores, failures and our learning curve. METHODS: Three hundred and twenty-three patients (403 limbs) with incompetence of the GSV underwent ELA. Patients were assessed by clinical examination and venous duplex ultrasound was performed 6 weeks after operation. Visual analog scale (VAS) pain scores of the first postoperative week were recorded. Operative time and success rate were analysed. RESULTS: After 6 weeks, 301 (74.7%) treated legs were examined by duplex ultrasound imaging. Successful complete occlusion was present in 282 (93.7%) GSVs. Partial occlusion was present in 12 (4.0%) GSVs. In seven (2.3%) limbs the GSV was not occluded. The maximum mean VAS pain score was noted on the 5th postoperative day. From the start of this series, the operation time decreased rapidly for each surgeon, stabilising after 15 limbs. CONCLUSION: ELA of the incompetent GSV is effective and safe. ELA is simple to perform, well accepted by patients and relatively atraumatic. In our opinion, ELA can be easily implemented in surgical practice.

[Endovenous laser therapy: a new treatment for varicose veins]. / Endoveneuze lasertherapie: een nieuwe behandeling van varices.

Varicose veins are very common. For years the most commonly applied treatment for great saphenous vein (GSV) insufficiency was saphenofemoral junction ligation with saphenous vein stripping. Minimally invasive methods, such as the endovenous laser therapy, are increasingly used during the last few years. In endovenous laser therapy, a diode laser fibre is inserted percutaneously into the GSV using ultrasonography to confirm the position. Thermal laser energy is applied to the endothelium ofthe GSV, resulting in local venous occlusion. The procedure has rapidly become popular with clinicians who treat varicose veins due to its relative simplicity and high rate of patient satisfaction. Efficacy outcomes are good with an occlusion rate of up to 100%. Recanalisation is rarely occurring even after several years. Pain, haematoma and phlebitis are common adverse events associated with endovenous laser therapy but in most cases are self-limiting. Serious adverse events, such as deep vein thrombosis, are uncommon. The advantages ofendovenous laser therapy are the lack of surgical wounds, so infection and scarring are avoided, and that the procedure can be performed in an outpatient setting using local anaesthesia. Endovenous laser therapy appears to be a safe and effective treatment option for refluxing varicose veins.

Cardiac failure following group A streptococcal infection with echocardiographically proven pericarditis, still insufficient arguments for acute rheumatic fever: a case report and literature update.

We recently encountered a 49-year-old female who developed fever due to group A streptococcal (GAS) bacteriaemia spreading to an abscess in the iliac muscle and a bacterial monarthritis of the right knee with a sterile arthritis of her left knee. Treatment was started with a six-week course of intravenous penicillin. She developed a mitral valve insufficiency and pericarditis on the tenth day of admission. In the third week heart failure developed with, on echocardiograph, a high output left ventricular failure without signs of valvulitis or myocarditis. Using a diuretic regimen she was recompensated. Because of the pericarditis with mitral valve insufficiency corticosteroids were given, which had a rapid beneficial effect. A discussion follows on the position of acute rheumatic fever versus post-streptococcal reactive arthritis in this clinical picture and the literature is updated.

Enteropathy-associated T-cell lymphoma presenting with eosinophilia.

Hypereosinophilia can be related to various diseases; when it occurs without an obvious cause it is called idiopathic hypereosinophilic syndrome (IHES). We describe a patient with increasing eosinophilia, which in spite of extensive diagnostic procedures initially remained unexplained. However, during follow-up it became apparent that this patient had a lethal enteropathy-associated T lymphoma (EATL) causing the hypereosinophilia.

Reduction of non-endothelial cell contamination of microvascular endothelial cell seeded grafts decreases thrombogenicity and intimal hyperplasia.

INTRODUCTION: fat derived microvascular endothelial cells (MVEC) seeded on prosthetic vascular grafts, improve patency in animals. Results in humans were disappointing, due to thrombogenicity and progressive intimal hyperplasia. Also in animals intimal hyperplasia was found. We postulate that contaminating cells present in the transplant are involved in the intimal hyperplasia. We developed a method to further purify human MVEC from 40-90%. Here we tested the effects of enrichment upon thrombogenicity and seeding-related intimal hyperplasia. METHODS: liposuction fat was enzymatically digested and centrifuged. To enrich MVEC, contaminating macrophages and fibroblasts were removed with dynabeads coated with macrophage- and fibroblast-specific antibodies. Thrombogenicity was assessed by measuring tissue factor and thrombomodulin activity, presence of endothelial nitric oxide synthase and via perfusion of the cells with whole blood. To investigate seeding-related intimal hyperplasia, PTFE grafts were seeded with the cells and cultured for 3 weeks. RESULTS: tissue factor activity of purified cells was reduced compared to nonpurified cells. Purified cells showed thrombomodulin activity and eNOS expression. Fragment 1+2 and Fibrinopeptide A generation after perfusion of purified cells were significantly lower than after perfusion of nonpurified cells, and only nonpurified cells were covered with platelets and fibrin. Prostheses seeded with nonpurified cells showed an EC monolayer above a multilayer of myofibroblasts, prostheses seeded with purified cells only showed a single EC monolayer. Mixing experiments with human umbilical cord EC (HUVEC) and fibroblasts showed that when more than 25% HUVEC were present a confluent EC layer was formed. When the amount of fibroblasts was 25% or less, no development of a subendothelial multilayer of myofibroblasts was found within 3 weeks. CONCLUSION: reduction of non-endothelial cell contamination of microvascular endothelial cell seeded grafts decreases thrombogenicity and might prevent seeding-related intimal hyperplasia.

Contaminants from the transplant contribute to intimal hyperplasia associated with microvascular endothelial cell seeding.

OBJECTIVES: seeding prosthetic grafts with fat-derived microvascular endothelial cells (MVEC) results not only in a non-thrombogenic EC layer, but also in intimal hyperplasia. Here we investigated incidence, composition, progression, and cause of this intimal hyperplasia. DESIGN: EPTFE grafts with MVEC were implanted as carotid interpositions in six dogs with 1 month, and in three dogs with 4, 8 and 12 months follow-up. Grafts seeded without cells, implanted in the contralateral carotid, served as a control. In another three dogs labelled cells were seeded to investigate the contribution of the seeded cells (2-3 weeks). MATERIALS AND METHODS: MVEC were isolated from the falciform ligament. Cells were pressure seeded on ePTFE grafts. Labelling was performed using retroviral gene transduction. The grafts were analysed with immunohistochemical techniques. RESULTS: after 1 month, all patent non-seeded grafts (5/6) showed fibrin and platelet deposition, and all patent seeded grafts (5/6) were covered with a confluent endothelial monolayer on top of a multilayer of myofibroblasts, elastin and collagen. After long term follow-up, all non-seeded grafts were occluded, all patent seeded grafts (4 and 12 months) were covered with an EC-layer with intimal hyperplasia underneath. The thickness of the intima did not progress after 1 month. Transduced cells were found in the endothelial monolayer, hyperplastic intima and luminal part of the prosthesis. CONCLUSIONS: MVEC seeding in dogs results in intimal hyperplasia in all patent grafts, which contains myofibroblasts. Contaminants from the transplant contribute to this intimal hyperplasia.