The Conflicting Prognostic Role of the Stroma-Tumor Ratio in Breast Cancer Molecular Subtypes.

The tumor microenvironment plays a key role in tumor progression. The proportion of the stroma-to-tumor cells (stroma-tumor ratio [STR]) has a variable prognostic significance in breast cancer (BC) molecular classes. In this study, we evaluated the mechanisms of stroma formation and composition in different molecular subtypes, which could explain the different prognostic values. This study interrogated 2 large well-characterized BC cohorts. Firstly, an in-house BC cohort (n = 822) encompassing all BC molecular subtypes from the Nottingham series was used. In each subtype, stromal assessment was carried out, and tumors were assigned to 2 groups: high and low STR, and further correlation with tumor characteristics and patient outcomes was investigated. The contribution of tumor-infiltrating lymphocytes (TILs) to the stroma has also been studied. Secondly, the public domain data set (The Cancer Genome Atlas data [TCGA], n = 978) was used as a validation cohort and for differential gene expression (DGE) analysis. DGE was performed to identify a set of genes associated with high STR in the 3 main molecular subtypes. High STR was associated with favorable patient outcomes in the whole cohort and in the luminal subtype, whereas high STR showed an association with poor outcomes in triple-negative BC (TNBC). No association with outcome was found in the HER2 enriched BC. DGE analysis identified various pathways in luminal and TNBC subtypes, with immune upregulation and hypoxia pathways enriched in TNBC, and pathways related to fibrosis and stromal remodeling enriched in the luminal group instead. Low STR accompanied by high TILs was shown to carry the most favorable prognosis in TNBC. In line with the DGE results, TILs played a major prognostic role in the stroma of TNBC but not in the luminal or HER2-enriched subtypes. The underlying molecular mechanisms and composition of the stroma in BC are variable in the molecular subtypes and explain the difference in its prognostic significance.

Predictors of moderate to severe obstructive sleep apnea in patients with lung cancer.

BACKGROUND AND OBJECTIVES: OSA is a known medical condition that is associated with several comorbidities and affect patients' quality of life. The association between OSA and lung cancer remains debated. Some studies reported increased prevalence of OSA in patients with lung cancer. We aimed to assess predictors of moderate-to-severe OSA in patients with lung cancer. METHODS: We enrolled 153 adult patients who were newly diagnosed with lung cancer. Cardiorespiratory monitoring was performed using home sleep apnea device. We carried out Univariate and multivariate logistic regression analysis on multiple parameters including age, gender, smoking status, neck circumference, waist circumference, BMI, stage and histopathology of lung cancer, presence of superior vena cava obstruction, and performance status to find out the factors that are independently associated with a diagnosis of moderate-to-severe OSA. RESULTS: Our results suggest that poor performance status is the most significant predictor of moderate to severe OSA in patients with lung cancer after controlling for important confounders. CONCLUSION: Performance status is a predictor of moderate to severe OSA in patients with lung cancer in our population of middle eastern ethnicity.

Geometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy.

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n = 100) and invasive tumours (n = 100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68 ± 11.2 fibre/µm2) compared to DCIS (p < 0.0001). The collagen fibres were thinner (13.78 ± 1.08 µm), straighter (0.96 ± 0.006, on a scale of 0-1), more disorganised (95.07° ± 11.39°) and less aligned (0.20 ± 0.09, on a 0-1 scale) in the invasive BC compared to DCIS (all p < 0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients' outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion.

Burden of obstructive sleep apnea in patients with lung cancer and its effect on performance status.

The association between lung cancer and obstructive sleep apnea has remained a matter of debate for years. Obstructive sleep apnea is thought to increase the incidence of lung cancer due to intermittent hypoxaemia and sleep fragmentation. The aim of this study is to assess the prevalence of obstructive sleep apnea in patients with lung cancer and its effect on those patients' performance status. This is a prevalence study that was conducted at Chest Diseases Department, Alexandria Main University Hospitals. We enrolled 153 patients with lung cancer. All patients underwent cardiorespiratory monitoring using a home sleep-testing device. Performance status was assessed using Karnofsky performance status scale. The study included 120 (78.4%) males and 33 (21.6%) females newly diagnosed with lung cancer. The mean age was 59.98 ± 11.11 years. Obstructive sleep apnea (apnea-hypopnea index ≥ 5) was present in 134 (87.6%) patients. Eighty-five (63.4%) patients had mild obstructive sleep apnea, 39 (29.1%) patients had moderate obstructive sleep apnea, and 10 (7.46%) patients had severe obstructive sleep apnea. Prolonged nocturnal oxygen desaturation as demonstrated by time of oxygen saturation spent below 90% (T90%) during total sleep time > 30% was present in 25 (16.3%) patients. There was a significant difference in the median value of Karnofsky performance status scale between patients with lung cancer and associated obstructive sleep apnea and those without obstructive sleep apnea. In conclusion, obstructive sleep apnea is highly prevalent among patients with lung cancer. Performance status is worse among patients with lung cancer in the presence of obstructive sleep apnea. Screening patients with lung cancer for obstructive sleep apnea is important regardless of the presence of classical symptoms of obstructive sleep apnea.

Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?

BACKGROUND: Encapsulated papillary carcinoma (EPC) is surrounded by a thick fibrous capsule-like structure, which is interpreted as a thickened basement membrane (BM). This study aimed to describe the geometric characteristics of the EPC capsule and to refine whether it is an expansion of the BM or a stromal reactive process. MATERIAL AND METHODS: In all, 100 cases were divided into four groups: EPC, ductal carcinoma in situ (DCIS), normal breast tissue and invasive tumours, with an additional encapsulated papillary thyroid carcinoma (EPTC) control group. Representative slides from each case were stained with picrosirius red (PSR) stain and examined using polarised microscopy. Images were analysed using ImageJ, CT-FIRE, and Curve align image analysis programmes. RESULTS: Compared to the normal and DCIS BM, the EPC group showed a significant increase of collagen fibre width, straightness, and density, and a decrease of fibre length. The EPC capsule showed less alignment of fibres with a more perpendicular arrangement, and it was enriched with disorganised collagen type I (stromal collagen) fibres. Compared to other groups, the EPC capsule showed significant variation in the thickness, evenness, distribution of collagen fibres, and significant intracapsular heterogeneity. Compared to BM-like material in the invasive group, the EPC capsule showed a higher density of collagen fibres with longer, straighter, and more aligned fibres, but there was no difference in the distribution of both collagen types I and III. Conversely, compared to EPTC, there were no differences between both EPC and EPTC capsules except that the fibres in the EPC capsule were straighter. Although differences between normal ducts and lobules and DCIS BM collagen fibre density, straightness, orientation, and alignment were detected, both were significantly different from EPC capsule. CONCLUSION: This study provided evidence that the EPC capsule is a reactive process rather than a thickened native BM characteristic of normal and in situ lesions, which provides further evidence that EPC is an indolent invasive carcinoma based on capsule characteristics.

Fatigue-related symptom clusters and functional status of older adults in hospice.

BACKGROUND: Fatigue is frequently co-existing with other symptoms and is highly prevalent among patients with cancer and geriatric population. There was a lack of knowledge that focus on fatigue clusters in older adults with cancer in hospice care. OBJECTIVES: To identify fatigue-related symptom clusters in older adult hospice patients and discover to what extent fatigue-related symptom clusters predict functional status while controlling for depression. METHOD: This was a cross-sectional study in a sample of 519 older adult hospice patients with cancer, who completed the Memorial Symptom Assessment Scale, the Center for Epidemiological Studies Depression, Boston Short Form Scale, and the Palliative Performance Scale. Data from a multi-center symptom trial were extracted for this secondary analysis using exploratory factor analysis and hierarchical multiple regression analysis. RESULTS: Data from 519 patients (78 ± 7 years) with terminal cancer who received hospice care under home healthcare services revealed that 39% of the participants experienced fatigue-related symptom clusters (lack of energy, feeling drowsy, and lack of appetite). The fatigue cluster was significantly associated positively with depression (r = 0.253, p < 0.01), and negatively with functional status (r = -0.117, p < 0.01) and was a strong predictor of participants' low functional status. Furthermore, depression made a significant contribution to this predictive relationship. CONCLUSION: Older adult hospice patients with cancer experienced various concurrent symptoms. The fatigue-specific symptom cluster was identified significantly associated with depression and predicted functional status. Fatigue should be routinely monitored in older adults, especially among hospice cancer patients, to help reduce psychological distress and prevent functional decline.

Home monitoring of lung function, symptoms and quality of life after admission with COVID-19 infection: The HOMECOMIN' study.

BACKGROUND AND OBJECTIVE: To develop targeted and efficient follow-up programmes for patients hospitalized with coronavirus disease 2019 (COVID-19), structured and detailed insights in recovery trajectory are required. We aimed to gain detailed insights in long-term recovery after COVID-19 infection, using an online home monitoring programme including home spirometry. Moreover, we evaluated patient experiences with the home monitoring programme. METHODS: In this prospective multicentre study, we included adults hospitalized due to COVID-19 with radiological abnormalities. For 6 months after discharge, patients collected weekly home spirometry and pulse oximetry measurements, and reported visual analogue scales on cough, dyspnoea and fatigue. Patients completed the fatigue assessment scale (FAS), global rating of change (GRC), EuroQol-5D-5L (EQ-5D-5L) and online tool for the assessment of burden of COVID-19 (ABCoV tool). Mixed models were used to analyse the results. RESULTS: A total of 133 patients were included in this study (70.1% male, mean age 60 years [SD 10.54]). Patients had a mean baseline forced vital capacity of 3.25 L (95% CI: 2.99-3.44 L), which increased linearly in 6 months with 19.1% (Δ0.62 L, p < 0.005). Patients reported substantial fatigue with no improvement over time. Nevertheless, health status improved significantly. After 6 months, patients scored their general well-being almost similar as before COVID-19. Overall, patients considered home spirometry useful and not burdensome. CONCLUSION: Six months after hospital admission for COVID-19, patients' lung function and quality of life were still improving, although fatigue persisted. Home monitoring enables detailed follow-up for patients with COVID-19 at low burden for patients and for the healthcare system.

Association of weekly strength exercise frequency and academic performance among students at a large university in the United States.

The study aimed to examine (a) the association between weekly strength exercise frequency and grade point average (GPA), and (b) the demographic characteristics of weekly strength exercise frequency among undergraduate students at a large southern state university in the United States. Health behavior data (N = 1125) collected by the American College Health Association at the university in 2008 were analyzed. Analysis of variance was used to investigate weekly strength exercise frequency differences in GPA, sex, ethnicity, and year in university. The results revealed that those who more frequently engaged in strength exercise had significantly higher GPA. There was a significant difference in weekly strength exercise frequency by sex and ethnicity. Findings suggest that regular engagement in strength exercise may not only have physical health benefits but is also associated with academic achievement in high education. There is a need to further investigate the mechanism of strength exercise on GPA among university students.

Defining invasion in breast cancer: the role of basement membrane.

Basement membrane (BM) is an amorphous, sheet-like structure separating the epithelium from the stroma. BM is characterised by a complex structure comprising collagenous and non-collagenous proteoglycans and glycoproteins. In the breast, the thickness, density and composition of the BM around the ductal lobular system vary during differing development stages. In pathological conditions, the BM provides a physical barrier that separates proliferating intraductal epithelial cells from the surrounding stroma, and its absence or breach in malignant lesions is a hallmark of invasion and metastases. Currently, diagnostic services often use special stains and immunohistochemistry (IHC) to identify the BM in order to distinguish in situ from invasive lesions. However, distinguishing BM on stained sections, and differentiating the native BM from the reactive capsule or BM-like material surrounding some invasive malignant breast tumours is challenging. Although diagnostic use of the BM is being replaced by myoepithelial cell IHC markers, BM is considered by many to be a useful marker to distinguish in situ from invasive lesions in ambiguous cases. In this review, the structure, function and biological and clinical significance of the BM are discussed in relation to the various breast lesions with emphasis on how to distinguish the native BM from alternative pathological tissue mimicking its histology.

[Early hospital discharge for patients with COVID-19: evaluation of the transmural healthcare program in Amsterdam]. / Vervroegd ontslag van patiënten met covid-19.

OBJECTIVE: Evaluation of an early discharge program for COVID-19-patients who still required additional oxygen support, supervised by their own general practitioner (GP) in a home setting. We evaluated safety and gathered experiences from patients, caregivers and GPs. DESIGN: Cohort study (prospective and retrospective inclusion) METHOD: Adult COVID-19-patients admitted to one of the three Amsterdam hospitals, the Netherlands, were eligible when clinically stable for at least 48 hours, with a minimum oxygen saturation of 94% and a maximum of 3 l/min oxygen support. Patients were included from 23-10-2020 to 26-03-2021. RESULTS: We included 113 patients, of whom 40 retrospectively . Median age was 58 years and median length of hospital stay 8 days. Four patients (3.7%) were readmitted within 14 days after discharge. Median duration of oxygen support at home was 8 days. Almost no home visits were conducted by GPs, but contact by telephone was regular (median 6 times in 2 weeks). All stakeholders reported feeling safe, able and confident while delivering the necessary (self) care. The program was graded by patients and GPs with an 8 (on a scale of 1 to 10). CONCLUSION: Early discharge for COVID-19-patients with a necessity for oxygen support, under supervision of the GP, is safe and was positively evaluated by all stakeholders involved.

Low frequency of community-acquired bacterial co-infection in patients hospitalized for COVID-19 based on clinical, radiological and microbiological criteria: a retrospective cohort study.

BACKGROUND: We defined the frequency of respiratory community-acquired bacterial co-infection in patients with COVID-19, i.e. patients with a positive SARS-CoV-2 PCR or a COVID-19 Reporting and Data System (CO-RADS) score ≥ 4, based on a complete clinical assessment, including prior antibiotic use, clinical characteristics, inflammatory markers, chest computed tomography (CT) results and microbiological test results. METHODS: Our retrospective study was conducted within a cohort of prospectively included patients admitted for COVID-19 in our tertiary medical centres between 1-3-2020 and 1-6-2020. A multidisciplinary study team developed a diagnostic protocol to retrospectively categorize patients as unlikely, possible or probable bacterial co-infection based on clinical, radiological and microbiological parameters in the first 72 h of admission. Within the three categories, we summarized patient characteristics and antibiotic consumption. RESULTS: Among 281 included COVID-19 patients, bacterial co-infection was classified as unlikely in 233 patients (82.9%), possible in 35 patients (12.4%) and probable in 3 patients (1.1%). Ten patients (3.6%) could not be classified due to inconclusive data. Within 72 h of hospital admission, 81% of the total study population and 78% of patients classified as unlikely bacterial co-infection received antibiotics. CONCLUSIONS: COVID-19 patients are unlikely to have a respiratory community-acquired bacterial co-infection. This study underpins recommendations for restrictive use of antibacterial drugs in patients with COVID-19.

Evaluation of transconjunctival frontalis suspension using nonabsorbable suture.

PURPOSE: To evaluate the transconjunctival frontalis suspension technique using nonabsorbable suture (4/0 polypropylene) in patients with severe blepharoptosis and poor levator function. METHODS: A total of 22 patients (33 ptotic eyelids) were included in a prospective interventional case series study. All had severe ptosis with poor levator function. Transconjunctival frontalis suspension using 4/0 polypropylene suture was done in all patients. RESULTS: Twelve patients (17 eyelids) had congenital ptosis, 6 patients (12 eyelids) had blepharophimosis, and 4 patients (4 eyelids) had traumatic ptosis. The surgical technique was easy and fast and surgical results in the 3 groups were good functionally and cosmetically. Recurrences in 3 eyelids (9%) happened after 3 years. Follow-up ranged from 1 to 4 years. CONCLUSIONS: Transconjunctival frontalis suspension technique is simple and time saving for treatment of severe ptosis with poor levator function. It gives good functional and cosmetic results. Healing was normal with no postoperative swelling or infection. 4/0 Polypropylene exhibits satisfactory results and easy manipulation.

A Primer on Interstitial Lung Disease and Thoracic Radiation.

Interstitial lung disease (ILD) is a term used to describe a heterogeneous group of lung disorders with characteristic clinical and imaging features. Patients with ILD are at an increased risk of developing NSCLC, which is frequently medically comorbid, often precluding operative management. In this scenario, radiotherapy (RT) is generally recommended; however, ILD is known to increase the risk of RT-related toxicity. Recommendations for treatment with appropriately individualized risks and benefits are thus dependent on integration of patient-, ILD-, and cancer-specific factors. We aim to provide an overview of ILD for the thoracic oncologist, an assessment of risk of thoracic RT in patients with ILD, and evidence-based recommendations for treatment in a variety of clinical scenarios.

Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma.

PURPOSE: To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL). PATIENTS AND METHODS: IC consisted of thiotepa 250 mg/m(2)/d days -9 through -7, busulfan 10 mg/kg (total dose) days -6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly. RESULTS: Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure. CONCLUSION: IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients > or = 60 years. A prospective multicenter study is ongoing.

Phase II trial of CPT-11 in myelodysplastic syndromes with excess of marrow blasts.

CPT-11 is an antineoplastic agent which acts as a specific inhibitor of DNA topisomerase 1 and has a broad spectrum of activity in solid tumors. Very few studies have evaluated the activity of CPT-11 in hematological malignancies. We conducted a phase II trial of CPT-11 in 26 patients with high-risk MDS (RAEB 1: n = 4; RAEB 2: n = 9; MDS having progressed to AML: n = 10; CMML: n = 3) who could not receive anthracycline/cytarabine intensive chemotherapy. Induction therapy consisted of four courses of CPT-11 given intravenously at 200 mg/m(2) every 2 weeks. Patient characteristics were: median age, 71 (range 51-77); sex, (M/F), 21/5, median % marrow blasts cells, 13.5 (range 7-52). Cytogenetics according to IPSS were: low-risk n = 13, intermediate-risk n = 6, high-risk n = 3, failure or not done n = 4. Six patients stopped treatment after only one or two courses of CPT-11 due to severe infection (n = 2), progressive disease (n = 3), acute lysis syndrome with renal failure (n = 1). In the 20 patients who received at least three cycles of CPT-11, complete remission was achieved in one case, partial remission in four cases, and hematological improvement in three cases with an overall response rate of 33% in the 26 patients. Duration of response was short (median 4 months, range 1-6 months) and median survival was 8 months (range 1-23 months). Digestive toxicity (diarrhea) occurred in 26/89 (29%) courses, but was mild (grade 1, 20% courses; grade 2 or 3, 9% courses). Hematological toxicity was difficult to assess in non-responders because of initial pancytopenia, but all the patients who responded had grade 3/4 hematological toxicity associated with grade >/=2 infection requiring hospitalization in 18% of the courses. No other major toxicity was observed. Thus CPT-11 has an interesting activity in MDS with excess of blasts; toxicity is easily managed and most patients can be treated in the out-clinic setting. These results suggest that further evaluation of CPT-11 in MDS is warranted.

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study.

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.

Aortic coarctation in the adult: management of complications and coexisting arterial abnormalities with hypothermic cardiopulmonary bypass and circulatory arrest.

OBJECTIVES: Adult patients with aortic coarctation may have complications after childhood repair. Other adult patients have coarctation and aneurysms of the aorta and the left subclavian artery. The optimal management of such cases is not clearly established. We evaluated the role of hypothermic cardiopulmonary bypass and circulatory arrest. METHODS: Thirteen adult patients (mean age 38 years) with coarctation and coexisting abnormalities of the aorta and left subclavian artery were treated. Five patients had pseudoaneurysms develop after bypass grafting (n = 3) or patch angioplasty (n = 2). These were detected a mean of 21 years (range 13-44 years) after the initial operation. Four pseudoaneurysms were asymptomatic, and 1 had ruptured. One patient had recurrent coarctation from fibrous obliteration of a 10-mm bypass graft inserted 15 years previously. The remaining 7 patients had aneurysms of the left subclavian artery (n = 5), aneurysms of the ascending aorta and arch (n = 1), or stenosis of the left subclavian artery (n = 1) in combination with moderate or severe coarctation. Resection and interposition graft replacement of the aneurysmal or stenotic aortic segments were performed in all cases with an interval of hypothermic circulatory arrest that averaged 44 +/- 5 minutes (range 33-54 minutes). Seven patients had interposition graft replacement of aneurysmal or stenotic left subclavian arteries. RESULTS: There were no in-hospital or late deaths (maximal follow-up 7 years). No patient had brain injury, paralysis, myocardial, respiratory, or renal failure. No patient has evidence of recurrent coarctation or aneurysm formation. CONCLUSIONS: Cardiopulmonary bypass with hypothermic circulatory arrest can safely be used in the treatment of complex adult coarctation. It permits accurate delineation of the anatomy with minimal dissection, avoidance of aortic clamping and sacrifice of intercostal arteries, precise interposition graft repair, and adequate protection of vital organs.

Single-stage reoperative repair of chronic type A aortic dissection using the arch-first technique.

BACKGROUND: Management of the enlarged, chronically dissected aorta after previous repair of acute ascending aortic dissection or after a previous cardiac operation may present a formidable technical challenge and the optimal method of management is not clearly established. METHODS: Twenty-one patients with chronic type A aortic dissection (mean age 57 years) underwent resection of the ascending aorta, the aortic arch, and varying segments of the descending thoracic aorta. Single-stage replacement with perfusion of the aortic arch first to minimize the duration of brain ischemia and a bilateral anterior thoracotomy (clamshell) incision were used. Fourteen patients had undergone previous repair of acute type A dissection. Seven patients had type A dissection after aortic valve replacement (3 patients) or coronary artery bypass (4 patients). Marked enlargement of the aorta distal to the left subclavian artery precluded a two-stage repair. The mean interval between the initial and reoperative procedures was 69 months (range, 5 to 249). RESULTS: There was 1 (4.8%) hospital death. Four patients required reoperation for bleeding. One patient required a right ventricular assist device that was successfully removed. Ten patients required assisted ventilation for more than 48 hours. All were successfully weaned from ventilatory support. No patient had a stroke or other adverse neurologic outcome. There has been 1 late death (mean follow-up 2 years). CONCLUSIONS: The single-stage, arch-first replacement technique is a safe and effective procedure for patients who require extensive reoperations for chronic expanding type A dissection.

Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with circulatory arrest is an important adjunct for operations on the distal aortic arch, the descending thoracic, and the thoracoabdominal aorta. The safety and efficacy of this technique when compared with other adjuncts (ie, simple aortic clamping, partial cardiopulmonary bypass, regional hypothermia) is not clearly established. METHODS: One hundred and ninety-two patients (age range, 20 to 83 years) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the involved aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest (mean, 38 minutes). The technique was used when the location and severity of disease precluded placement of clamps on the proximal aorta (31 patients) or (in 161 patients) when extensive thoracic (47) or thoracoabdominal (114) aortic disease was present, and the risk for development of spinal cord ischemic injury was judged to be increased. Lower intercostal and lumbar arteries were attached separately to the aortic graft in 101 of the 161 patients (63%) who had extensive aortic replacement. No other adjuncts for spinal cord protection were used. RESULTS: The 30-day mortality was 6.8% (13 patients). It was 40% (8 of 20) for patients having emergent operations (acute aortic dissection or rupture) and 2.9% (5 of 172) for all others (p < 0.001). The 90-day mortality was 12.5% (24 patients). Paraplegia occurred in 4 and paraparesis in 1 (full recovery) of the 186 operative survivors whose lower limb function could be assessed postoperatively (2.7%). Among the 109 survivors with thoracoabdominal aortic disease, early paraplegia occurred in 1 of 36 with Crawford extent I, 0 of 42 with extent II, and 2 of 31 with extent III disease. One patient (extent II) developed paraplegia on the 9th postoperative day after a hypotensive episode. None of the 47 patients with aortic dissection developed paralysis. Among the 186 operative survivors, renal dialysis was required in 4 patients (2.2%), prolonged inotropic support in 18 (10%), reoperation for bleeding in 9 (5%), mechanical ventilation (> or = 48 hours) in 64 (34%), and tracheostomy in 17 (9%). Four patients (2%) sustained a stroke. CONCLUSIONS: Hypothermic cardiopulmonary bypass with circulatory arrest provides safe and substantial protection against paralysis and renal, cardiac, and visceral organ system failure that equals or exceeds that of other currently used techniques but without the need of other adjuncts.