Transpleural systemic artery-to-pulmonary artery communications in the absence of chronic inflammatory lung disease. A case series and review of the literature.

AIM: To describe the causes and computed tomography (CT) and angiographic appearances of transpleural systemic artery-to-pulmonary artery shunts in patients without chronic inflammatory lung disease and determine their best management. MATERIALS AND METHODS: All patients referred to a tertiary referral unit between January 2009 and January 2020 in whom a diagnosis of a systemic-to-pulmonary artery communication without underlying chronic inflammatory lung disease was subsequently made have been included in this report. Medical records and imaging findings were reviewed retrospectively. RESULTS: Ten patients (male: female ratio = 7:3; median age 42 years [range 22-70 years]) with systemic artery-to-pulmonary artery shunts without chronic inflammatory lung disease were identified. Five were misdiagnosed as having a pulmonary arteriovenous malformation and had been referred for embolisation. In six patients, there was either a history of accidental or iatrogenic thoracic trauma or of inflammatory disease involving the pleura, and in two patients, in whom a previous medical history could not be obtained, there were CT features suggesting previous pleural inflammatory disease. Two shunts were thought to be congenital. All individuals were asymptomatic other than one with localised thoracic discomfort that dated from the time of surgery. All patients were managed conservatively and have remained well with a median follow-up of 4.5 years (range 1-11.3 years). CONCLUSIONS: Localised transpleural systemic artery-to-pulmonary artery shunts in the absence of chronic inflammatory lung disease are usually related to previous thoracic trauma/intervention or abdominal or pulmonary sepsis involving a pleural or diaphragmatic surface. Congenital shunts are rare. The present study and much of the literature supports conservative management.

Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) generate a right-to-left shunt. Impaired gas exchange results in hypoxaemia and impaired CO2 clearance. Most patients compensate effectively but some are dyspneic, and these are rarely the most hypoxaemic. AIM: To test degrees of concurrent pathology influencing exercise capacity. DESIGN: Replicate, sequential single centre, prospective studies. METHODS: Cardiopulmonary exercise tests (CPETs) were performed in 26 patients with PAVMs, including individuals with and without known airflow obstruction. To replicate, relationships were tested prospectively in an independent cohort where self-reported exercise capacity evaluated by the Veterans Specific Activity Questionnaire (VSAQ) was used to calculate metabolic equivalents (METs) at peak exercise (n = 71). Additional measurements included oxygen saturation (SpO2), forced expiratory volume in 1 s (FEV1), vital capacity (VC), fractional exhaled nitric oxide (FeNO), haemoglobin and iron indices. RESULTS: By CPET, the peak work rate was only minimally associated with low SpO2 or low arterial oxygen content (calculated as CaO2=1.34 × SpO2 × haemoglobin), but was reduced in patients with low FEV1 or VC. Supranormal work rates were seen in patients with severe right-to-left shunting and SpO2 < 90%, but only if FEV1 was >80% predicted. VSAQ-calculated METS also demonstrated little relationship with SpO2, and in crude and CaO2-adjusted regression, were lower in patients with lower FEV1 or VC. Bronchodilation increased airflow even where spirometry was in the normal range: exhaled nitric oxide measurements were normal in 80% of cases, and unrelated to any PAVM-specific variable. CONCLUSIONS: Exercise capacity is reduced by relatively mild airflow limitation (obstructive or restrictive) in the setting of PAVMs.

Flightless I is a key regulator of the fibroproliferative process in hypertrophic scarring and a target for a novel antiscarring therapy.

BACKGROUND: Hypertrophic scarring carries a large burden of disease, including disfigurement, pain and disability. There is currently no effective medical treatment to reduce or prevent hypertrophic scarring. Flightless I (Flii), a member of the gelsolin family of actin remodelling proteins, is an important negative regulator of wound repair. OBJECTIVES: The objective of this study was to investigate the role of Flii as a potential regulator of hypertrophic scarring. METHODS: Using human skin samples and an animal model of bleomycin-induced hypertrophic scarring in mice that overexpress or have reduced expression of Flii, we investigated its effect on dermal fibrosis and hypertrophic scarring. RESULTS: Flii expression was increased in human burns and hypertrophic scars. A similar increase in Flii was observed in hypertrophic scars formed in mice post-treatment with bleomycin. However, Flii-deficient (Flii(+/-) ) mice had reduced scarring in response to bleomycin evidenced by decreased dermal thickness, smaller cross-sectional scar areas, fewer myofibroblasts and a decreased collagen I/III ratio. In contrast, bleomycin-treated Flii-overexpressing mice (Flii(Tg/Tg) ) showed increased scar dermal thickness, larger cross-sectional scar areas, more myofibroblasts and an increased collagen I/III ratio. Injecting developing scars with a Flii neutralizing antibody led to a significant reduction in the size of the scars and a reduction in the collagen I/III ratio. CONCLUSIONS: This study identifies Flii as a profibrotic agent that contributes to excessive scar formation. Reducing its activity using neutralizing antibodies is a promising approach for reducing hypertrophic scarring.

Patterns of disease in patients at a tertiary referral centre requiring reoperative parathyroidectomy.

INTRODUCTION: Reoperative parathyroidectomy is required when there is persistent or recurrent hyperparathyroidism following the initial surgery (at least 5% of parathyroidectomies nationally). By convention, 'persistent disease' is defined as the situation where the patient has not been cured by the first operation. The term 'recurrent hyperparathyroidism' is used when the patient was confirmed to be biochemically cured for six months from the first operation but has hyperparathyroidism after this date. Reoperative surgery is associated with higher rates of postoperative complications as well as a greater rate of failure to cure. The aim of our study was to review our departmental experience of reoperative parathyroidectomy, with a view to identify patterns of disease persistence and recurrence. METHODS: Using a departmental database, patients were identified who had undergone reoperative parathyroidectomy between 2006 and 2014. All the pre, intra and postoperative information was documented including the operative note so as to record the location of the abnormal parathyroid gland found at reoperation. RESULTS: Almost two-thirds (63%) of patients had negative, equivocal or discordant conventional imaging so secondary investigative tools were required frequently. The majority of abnormal glands were found in eutopic locations. The most common locations for ectopic glands were intrathyroidal, mediastinal and intrathymic. A third (33%) of the patients had multigland disease and over a quarter (28%) had coexisting thyroid disease. CONCLUSIONS: Persistent hyperparathyroidism represents a challenging patient subgroup for which access to all radiological modalities and intraoperative parathyroid hormone monitoring are required. Patient selection for reintervention is a key determinant in the reoperation cure rate.

Pulmonary arteriovenous malformations and their mimics.

Pulmonary arteriovenous malformations (PAVMs) are abnormal communications between the pulmonary arteries and veins, which result in a right-to-left (R-L) shunt with resultant hypoxemia, the severity of which will depend upon the size and number of lesions. Most PAVMs occur in individuals with hereditary haemorrhagic telangiectasia (HHT) and are a cause of serious morbidity and mortality largely related to cerebrovascular complications secondary to paradoxical embolization. The importance of their recognition and treatment by embolization, even in the absence of symptoms, is well known. Their appearances on chest radiographs are often, but not always, characteristic and the CT appearances are diagnostic; however, there are a number of both vascular and non-vascular diseases that can cause confusion. This review serves to highlight these PAVM "mimics".

Optimizing the outcome of vascular intervention for Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA) predisposes to the development of arterial stenoses and aneurysms, and is associated with considerable morbidity and mortality amongst young patients. The aims of this study were to analyse indications and outcomes of surgical intervention, and to assess the potential benefits of immunosuppression and the use of perioperative imaging. METHODS: This was a retrospective review of patients with TA referred between 2001 and 2012. RESULTS: A series of 97 patients with TA, seen at a single tertiary centre, is reported. Immunosuppression was required in 87 patients (90 per cent). Thirty-seven (38 per cent) underwent 64 procedures: 27 patients underwent 33 open surgical procedures and 20 patients had 31 endovascular procedures. After a median follow-up of 6 years, the overall success rate was 79 per cent for open surgery (mean graft patency 9.4 years) and 52 per cent for endovascular procedures (P = 0.035). Procedural failure was significantly reduced in patients receiving preoperative immunosuppression, and particularly endovascular procedures (P = 0.001). In addition to clinical examination and measurement of acute-phase reactants, combination non-invasive imaging including Doppler ultrasonography, [18F]fluorodeoxyglucose combined positron emission and computed tomography (CT), magnetic resonance angiography and CT angiography was used to identify arterial lesions, establish the diagnosis and monitor treatment outcomes. CONCLUSION: Outcomes of vascular intervention in TA may be improved by detailed preoperative assessment including measurement of disease activity, and by ensuring optimal immunomodulatory therapy before and after the procedure.

Infective aneurysm of the inferior pancreaticoduodenal artery.

INTRODUCTION: Pancreaticoduodenal (PD) artery aneurysms account for less than 2% of all splanchnic aneurysms. A mycotic aetiology is extremely uncommon. INTRODUCTION: Two weeks following an episode of sepsis related to a prostatic biopsy, a 59-year-old man presented with abdominal pain and anaemia. Ultrasonography and computed tomography revealed an inferior PD artery pseudoaneurysm with an associated mesenteric root haematoma. This was treated successfully by transcatheter embolisation. INTRODUCTION: Infective pseudoaneurysms of the PD artery are rare but can be associated with rupture into the gastrointestinal tract or retroperitoneum. Transcatheter embolisation remains the most effective therapy as it is associated with low morbidity and mortality rates and recurrence is very unlikely provided the aneurysm is completely excluded from the circulation.

Laparoscopic management of insulinomas.

BACKGROUND: Conventional surgical management of insulinomas involves an open technique. The laparoscopic approach has advantages in terms of improved postoperative pain and recovery time. This retrospective study evaluated the laparoscopic management of pancreatic insulinomas. METHODS: Between December 2000 and March 2007, 23 patients were referred for consideration of laparoscopic insulinoma resection. Two patients were not deemed appropriate for the laparoscopic approach and were managed with open surgery. All surgery was performed by one experienced pancreatic surgeon. Laparoscopic intraoperative ultrasonography was not available for the first six procedures, but was used thereafter. RESULTS: Twenty-one patients (five men and 16 women, median age 46 (range 22-70) years) had a successful resection. All had single tumours, five in the head, nine in the body and seven in the tail of the pancreas. One conversion to open operation was performed in a patient with an insulinoma in the head of the pancreas who had dense adhesions resulting from pancreatitis. Three patients developed a postoperative pancreatic fistula. There has been no recurrence of symptoms in any patient. CONCLUSION: Laparoscopic management of insulinomas is feasible and safe. Laparoscopic intraoperative ultrasonography is a promising adjunct to the procedure, even after accurate preoperative localization.

Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services.

OBJECTIVES: Hereditary haemorrhagic telangiectasia (HHT) affects 1 in 5-8000 individuals. Pregnancy outcomes are rarely reported. The major reason is that most women do not have their HHT diagnosed prior to pregnancy. Using a large well-characterised series, we studied all pregnancies known to have occurred in HHT-affected women, whether or not their diagnosis was known at the time of pregnancy. Our aim was to estimate rates and types of major complications of HHT in pregnancy, to guide management decisions. DESIGN: Cohort study, with prospective, retrospective and familial components. SETTING/POPULATION: Tertiary referral centre population. METHODS: All 262 pregnancies in the 111 women with HHT and pulmonary arteriovenous malformations (PAVMs) reviewed between 1999 and 2005 were studied. Eighty-two women (74%) did not have a diagnosis of HHT/PAVM at the time of pregnancy. 222 pregnancies in their 86 HHT-affected relatives were also studied. MAIN OUTCOME MEASURES: PAVM bleed, stroke and maternal death. RESULTS: Thirteen women experienced life-threatening events during pregnancy: 1.0% (95% CI 0.1-1.9) of pregnancies resulted in a major PAVM bleed; 1.2% (0.3-2.2%) in stroke (not all were HHT related); and 1.0% (0.13-1.9%) in maternal death. All deaths occurred in women previously considered well. In women experiencing a life-threatening event, prior awareness of HHT or PAVM diagnosis was associated with improved survival (P = 0.041, Fisher's exact test). CONCLUSIONS: Most HHT pregnancies proceed normally. Rare major complications, and improved survival outcome following prior recognition, means that pregnancy in a woman with HHT should be considered high risk. Recommendations for pregnancy management are provided.

Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure.

Increasing evidence supports the use of embolisation to treat pulmonary arteriovenous malformations (AVMs). Most pulmonary AVM patients have hereditary haemorrhagic telangiectasia (HHT), a condition that may be associated with pulmonary hypertension. The current authors tested whether pulmonary AVM embolisation increases pulmonary artery pressure (P(pa)) in patients without baseline severe pulmonary hypertension. P(pa) was measured at the time of pulmonary AVM embolisation in 143 individuals, 131 (92%) of whom had underlying HHT. Angiography/embolisation was not performed in four individuals with severe pulmonary hypertension, whose systemic arterial oxygen saturation exceeded levels usually associated with dyspnoea in pulmonary AVM patients. In 143 patients undergoing pulmonary AVM embolisation, P(pa) was significantly correlated with age, with the most significant increase occurring in the upper quartile (aged >58 yrs). In 43 patients with repeated measurements, there was no significant increase in P(pa) as a result of embolisation. In half, embolisation led to a fall in P(pa). The maximum rise in mean P(pa) was 8 mmHg: balloon test occlusion was performed in one of these individuals, and did not predict the subsequent rise in P(pa) following definitive embolisation of the pulmonary AVMs. In the present series of patients, which excluded those with severe pulmonary hypertension, pulmonary artery pressure was not increased significantly by pulmonary arteriovenous malformation embolisation.

Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia.

BACKGROUND: Brain abscesses and ischaemic strokes complicate pulmonary arteriovenous malformations (PAVMs). At risk individuals are poorly recognised. Stroke/abscess risk factors have not been defined. METHODS: A cohort study of 323 consecutive individuals with PAVMs (n = 219) and/or the commonly associated condition hereditary haemorrhagic telangiectasia (HHT, n = 305) was performed. Most of the 201 individuals with PAVMs and HHT had no respiratory symptoms, and were unaware they had HHT. Anderson-Gill models assessed constant and time dependent potential predictive variables for stroke/abscess, and rate reduction by PAVM embolisation. RESULTS: 57 individuals with PAVMs and HHT experienced brain abscess or ischaemic stroke, usually prior to the diagnosis of underlying PAVMs/HHT. The primary determinants of stroke and abscess risks were unrelated to severity of PAVMs. Males had higher brain abscess rates (hazard ratio 3.61 (95% CI 1.58, 8.25), p = 0.0024); interventional histories and bacteriological isolates suggested dental sources. Once adjusted for gender, there was a marginal association between brain abscess and low oxygen saturation. For ischaemic stroke, there was no association with any marker of PAVM severity, or with conventional neurovascular risk factors. Surprisingly, low mean pulmonary artery pressure was strongly associated with ischaemic stroke (hazard ratio 0.89 (95% CI 0.83, 0.95) per mm Hg increase; p = 6.2x10(-5)). PAVM embolisation significantly reduced ischaemic stroke rate (p = 0.028); no strokes/abscesses occurred following obliteration of all angiographically visible PAVMs. The mean PAVM diagnosis-treatment interval was longer, however, when neurological risks were unrecognised. CONCLUSIONS: Ischaemic strokes and brain abscesses occur commonly in undiagnosed HHT patients with PAVMs. Risk reduction could be improved.

Mid-trimester dilation and evacuation with laminaria does not increase the risk for severe subsequent pregnancy complications.

OBJECTIVE: To evaluate subsequent pregnancy outcomes in women with a previous mid-trimester (12-24 weeks) pregnancy termination by dilation and evacuation (D&E) as compared to women without a previous D&E. METHOD: Medical records for women who underwent a D&E between 1995 and 2003 were identified and reviewed. Women with subsequent pregnancies were compared on a 1:2 basis with women in a control group who had viable pregnancies and no previous mid-trimester DE. Outcomes of interest included preterm labor, placental abnormalities, and a composite complication outcome. RESULTS: Of the 317 women who underwent a D&E, 85 had viable subsequent pregnancies. These women delivered slightly earlier than the 170 controls (38.9 versus 39.5 weeks, p=0.001), although there was no statistically significant difference between the two groups with regard to birth weights, spontaneous preterm delivery, abnormal placentation, and overall complication rate. CONCLUSIONS: Mid-trimester termination by D&E does not increase the rate of clinically significant subsequent pregnancy complications.

Pulmonary artery-to-pulmonary artery anastomoses: angiographic demonstration in patients with chronic thromboembolic pulmonary hypertension.

AIM: To describe direct pulmonary artery-to-pulmonary artery anastomoses seen at pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension and discuss their possible significance. MATERIALS AND METHODS: Between 1 August 2000 and 31 July 2004 43 patients (male-to-female ratio 25:18) with a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) underwent selective pulmonary angiography to assess the extent of disease and suitability for surgical pulmonary endarterectomy. The mean pulmonary artery pressure ranged from 27-84 mmHg (average of 51 mmHg). Selective bilateral digital subtraction pulmonary angiograms performed in all individuals were reviewed for the presence of intrapulmonary collaterals. RESULTS: In 15 of the 43 patients (male-to-female ratio =7:8) definite (n = 12) or probable (n = 3) pulmonary artery-to-pulmonary artery anastomoses were demonstrated. Of the remaining 28 patients in whom intrapulmonary collaterals were not seen it was felt that in 16 the angiograms were of insufficient diagnostic quality (grades 4-5) to exclude their presence. Twelve patients, eight of whom had angiograms of sufficient diagnostic quality (grades 1-3), demonstrated one or more areas of luxury perfusion but intrapulmonary collaterals were not seen. CONCLUSION: Direct pulmonary artery-to-pulmonary artery anastomoses were demonstrated in patients with chronic thromboembolic pulmonary hypertension, which to our knowledge have not been previously described. The importance of these collateral vessels is unclear but they may play a role in the maintenance of pulmonary parenchymal viability in patients with chronic pulmonary embolic disease. The rate of development of these collaterals and their prognostic significance in patients with chronic thromboembolic pulmonary hypertension are areas worthy of further study.

Spontaneous rupture of a true uterine artery aneurysm: a cause of retroperitoneal haematoma.

We report the first case of spontaneous rupture of a true uterine artery aneurysm in a 69-year-old woman presenting with severe abdominal pain, a left iliac fossa mass, anaemia and a retroperitoneal haematoma on CT scanning. In this patient, the aneurysm was successfully embolised using microcoils. The different imaging modalities used for diagnosis and the treatment options are discussed.

Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22,061 years of HHT patient life.

BACKGROUND: The frequency of haemorrhage in individuals with hereditary haemorrhagic telangiectasia (HHT), 10% of whom will have cerebral arteriovenous (AV) malformations, could be high enough to justify screening. This would allow presymptomatic treatment to prevent early onset stroke in a condition that affects at least 1 in 8000 individuals. This is an important issue in view of the contrast between transatlantic management approaches, the worldwide dissemination of patient information, and the ethical implications of the diagnosis for the untreated patient. OBJECTIVES: To define the annual incidence of haemorrhagic stroke in individuals with HHT. METHODS: Retrospective study on stroke incidence in individuals with HHT and their immediate families (n = 674; 22,061 HHT patient years), specifically analysing patients under 46 years of age (17,515 patient years). The results were compared with stroke risk in the general population. RESULTS: In the majority of cases, the haemorrhage was the first significant neurological event. Overcorrecting for any bias towards overestimation that would be introduced in excluding non-penetrant family members, cerebral haemorrhages were more than 20 times more common in male HHT subjects under the age of 45 years than in the general population (standardised ratio 22.99; 95% confidence interval, 13.14 to 37.33). Haemorrhages were also six times more common in female HHT subjects (6.18; 2.27 to 13.45). The incidence ratio of cerebral haemorrhage in male patients (1.84; 1.05 to 2.99) yielded a haemorrhage rate in individuals with cerebral AV malformations of 1.4-2.0% per annum, comparable to figures in the non-HHT cerebral AV malformation population. CONCLUSIONS: These data contradict accepted wisdom in many countries that asymptomatic HHT patients are at a low (and acceptable) risk of haemorrhage. The data justify a more aggressive screening approach to identify small causative lesions amenable to treatment.