Trileaflet Semilunar Valve Reconstruction: Acute Porcine in Vivo Evaluation.

Objective: The surgical treatment of malformed semilunar valves in congenital heart defects is challenging in terms of providing both longevity and the potential to grow with the recipient. We investigated a new surgical technique "Trileaflet Semilunar Valve Reconstruction" in an acute porcine model, a technique with geometrical properties that could remain sufficient and allow for some growth with the child. Methods: An acute 60-kg porcine model was used. With echocardiography, baseline pulmonary valvular geometry and hemodynamics were investigated. On cardiopulmonary bypass, the pulmonary leaflets were explanted, and the Trileaflet Semilunar Valve Reconstruction was performed with customized homograft-treated pericardial neo-leaflets. Off bypass, hemodynamics was reassessed. Results: Twelve animals were investigated. The neo-valves were found sufficient in ten animals and with minimal regurgitation in two animals. The neo-valve had a peak gradient of 3 ± 2 mm Hg with a peak velocity of 0.8 ± 0.2 m/s. The coaptation in the neo-valve had a mean increase of 4 ± 3 mm, P < .001. The neo-valve had a windmill shape in the echocardiographic short-axis view, and the neo-leaflets billowed at the annular plane in the long-axis view. Conclusions: In this acute porcine model, the neo-valve had no clinically significant regurgitation or stenosis. The neo-valve had an increased coaptation, a windmill shape, and leaflets that billowed at the annular plane. These geometric findings may allow for sustained sufficiency as the annular and pulmonary artery dimension increase with the child's growth. Further long-term studies should be performed to evaluate the efficacy and the growth potential.

A handsewn pericardial valved pulmonary conduit: pulsatile flow loop in vitro and acute porcine in vivo evaluation.

OBJECTIVES: Right ventricle to pulmonary artery anatomic discontinuity is common in complex congenital heart malformations. Handsewn conduits are a practised method of repair. In a proof-of-concept study, we evaluated pulmonary valve replacement with a handsewn pericardial valved pulmonary conduit in vitro and in vivo. METHODS: A pulsatile flow-loop model (in vitro) and an acute 60-kg porcine model (in vivo) were used. With echocardiography and pressure catheters, baseline geometry and fluid dynamics were measured. The pulmonary valve was replaced with a handsewn glutaraldehyde-treated pericardial valved pulmonary conduit corresponding to a 21-mm prosthetic valve, after which geometric measurements and fluid dynamics were reassessed. RESULTS: In vitro, 15 pulmonary trunks at 4 l/min and 13 trunks at 7 l/min, and in vivo, 11 animals were investigated. The valved pulmonary conduit was straightforward to produce at the operating table and easy to suture in place. All valves were clinically sufficient in vitro and in vivo. The mean transvalvular pressure gradient in the native valve and the conduit was 8 mmHg [standard deviation (SD): 2] and 7 mmHg (SD: 2) at 4 l/min in vitro, 19 mmHg (SD: 3) and 17 mmHg (SD: 4) at 7 l/min in vitro and 3 mmHg (SD: 2) and 6 mmHg (SD: 3) in vivo. CONCLUSIONS: Our proof-of-concept demonstrates no early evidence of structural damage to the conduit, and the fluid dynamic data were acceptable. The handsewn conduit can be produced at the operating table.

Fatigue and quality of life in patients with neuroendocrine neoplasia.

INTRODUCTION: Neuroendocrine Neoplasms (NEN) are rare tumours arising in the gastro-intestinal tract or lungs. Poor health related quality of life (HRQoL) is associated with the carcinoid syndrome (CS), but fatigue is also important. We aimed to quantify HRQoL and fatigue in out-patients with NEN. METHODS: In a cross-sectional study, we included 231 patients with NEN (G1-G3). We used pre-validated questionnaires MFI-20, EQ-5D-5L and 85% responded. We collected clinical, biochemical, imaging, and pathology data from Electronic Patient files. Normative values for fatigue and HRQoL were derived from background populations. RESULTS: Median age was 68 years (range 21-91) and 52% were male. Patients with NEN reported more fatigue and worse HRQoL compared to the background population (p < .05). Cured patients reported higher HRQoL than patients with current disease, and patients with high grade neoplasms (G2-G3) reported more anxiety and depression compared to patients with low grade G1 disease (p < .05). The CS resulted in a 9% relative loss in Quality Adjusted Life Years compared to patients without CS. (p < .05). More than 50% of patients with CS reported problems with usual activities, pain/discomfort, and anxiety/depression. Overall, 36% of patients with NEN were fatigued and 92% of these had psychological fatigue. Younger patients (<65 years) experienced more fatigue than older patients (p < .05). CONCLUSION: Patients with NEN report significantly lower HRQoL and more fatigue compared to the background population. Especially, patients with CS had pain, discomfort, anxiety, and depression and a relative reduction in HRQoL. However, compared to other cancer types, patients with NEN experience less fatigue.

Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients.

Introduction: The European Neuroendocrine Tumor Society, ENETS, reports variables of prognostic significance in pancreatic neuroendocrine tumors (PNET). However, studies have short follow-ups, and the optimal treatment remains controversial. We aimed to determine overall survival (OS), progression-free survival (PFS) after conservative treatment, and recurrence-free survival (RFS) after surgery and further to find predictors of aggressive PNET behavior to support treatment decisions. Methods: 174 patients with PNET treated at Aarhus University Hospital from 2011 to 2021 were included in a retrospective cohort study. Patients were divided into surgically resected (SUR, n=91) and medically or conservatively treated (MED, n=83). Variables were tested in univariate and multivariate survival analysis. Median follow-up time was 3.4 years in the MED group and 4.5 years in the SUR group. Results: The 5-year OS was 95% and 65% for the SUR and MED groups, respectively. The 5-year RFS in the SUR group was 80% whereas the 5-year PFS in the MED group was 41%. Larger tumor size, Ki67 index, tumor grade, and stage were predictive of shorter OS, RFS, and PFS. Further, chromogranin A was a predictor of OS. Larger tumor size was associated with higher stage and grade. Only 1 of 28 patients with stage 1 disease and size ≤2 cm developed progression on a watch-and-wait strategy during a median follow-up of 36 months. Conclusion: This study supported the ENETS staging and grading system to be useful to predict OS, PFS, and RFS in PNET. Further, our data support that small, localized, low-grade PNETS can be followed with active surveillance.

First-generation somatostatin ligand receptor treatment in a pregnant patient with a neuroendocrine tumor with liver metastases.

SUMMARY: This rare case describes the course of a pregnancy in a patient with a disseminated small intestinal neuroendocrine tumor. The patient received treatment with first-generation somatostatin ligand receptor (SLR) every 4 weeks and had stable disease for several years before her pregnancy. First-generation SLR treatment was initially paused after detection of the pregnancy. During pregnancy, the patient experienced moderate gastro-intestinal discomfort and fatigue, which was considered predominantly pregnancy related. However, since symptoms could be linked to the patient's cancer, treatment was resumed after the first trimester. Chromogranin-A measurements remained stable throughout pregnancy and was paralleled by the absence of diarrhea and only minor flushing. She gave birth by elective caesarean section in week 37 to a healthy baby. Subsequent follow up imaging immediately after and 10 months postpartum showed no disease progression. The safety profile of SLR treatment during pregnancy in the context of disseminated neuroendocrine tumors (NET) is discussed. LEARNING POINTS: Neuroendocrine neoplasms (NEN) are rare cancers often occurring in the gastro-intestinal tract or lungs. Many patients with NEN live for several years with disseminated disease. SLR treatment has been given to pregnant patients before; often patients with acromegaly. Pregnancies are reported uneventful. This patient completed an uneventful pregnancy while receiving SLR treatment for disseminated neuroendocrine disease and gave birth to a healthy baby. More research regarding long term effects and safety signals of SLR treatment during pregnancy are much needed.