Considerations in the Surgical Management of Unicuspid Aortic Stenosis.

Unicuspid aortic valve (UAV) stenosis is a rare condition accounting for 5% of non-rheumatic aortic stenosis. The diagnosis can be difficult to make prior to surgical intervention and transesophageal echocardiography has been demonstrated to be more accurate in making the diagnosis compared to transthoracic echocardiography. The presence of a posteriorly located aortic orifice on the short-axis views, with one or two visible raphe anteriorly; the absence of commissures (acommissural); or the presence of a lone commissure (unicommissural) between the left and noncoronary, or the left and right cusps suggests the diagnosis. Patients with UAV are predominantly males and present with stenosis about a decade earlier than those with the more prevalent bicuspid aortic valves (BAV). They more commonly present with aortic annular dilatation and have fewer comorbidities at presentation compared to patients with BAV. Surgical management of UAV stenosis includes aortic valve replacement through standard open heart surgery or percutaneous transcatheter aortic valve replacement (TAVR), aortic valve repair either by bicuspidization, tricuspidization or trileaflet reconstruction, or the Ross procedure. Patients with UAV stenosis require less concomitant coronary or other cardiac procedures when they need surgical intervention, but are about a decade younger at the time of their death. UAV stenosis is a distinct congenital anomaly with a different natural course than BAV. Surgical management should be individualized based on the patient's age at presentation, aortoannular anatomy, and associated cardiac conditions.

Surgical Correction of Aberrant Right Coronary Anomalies Stranding an Aortic Commissure with and Without Unroofing.

The technique for successful surgical correction of an anomalous origin of the right coronary artery from the opposite aortic cusp with an aberrant course between the aorta and pulmonary artery is illustrated in a symptomatic 62-year-old woman. The intramural course of the right coronary artery traversed the tip of the commissure between the anterior and posterior leaflets, and its repair entailed unroofing of the intramural segment from inside the aortic intima. This technique required resuspension of the overlying commissure to maintain optimal aortic valve leaflet coaptation and prevent aortic insufficiency. Modifications of this technique have been utilized by us whenever the intramural segment traversed behind the commissure. In these cases, partial or subtotal unroofing of the intramural segment was performed to preserve the integrity of the intima behind the overlying commissure. More recently, we have performed the surgical correction by probing the intramural segment within the aortic wall to its most anterior location and then performing a wide anterior unroofing in the aortic intima, and marsupializing the aortic and coronary intima to avoid dissection or intimal flap development. We favor utilizing these techniques of anatomic correction of the anomalous coronary to other techniques involving coronary artery bypass grafting of the anomalous coronary, especially in adult patients, as unroofing provides more lasting results.

Diagnosis and management of primary effusion lymphoma in the immunocompetent and immunocompromised hosts.

Primary effusion lymphoma (PEL) is an uncommon non-Hodgkin lymphoma associated with human herpes virus-8 (HHV-8) that grows mainly in serous body cavities. The most common presentation of PEL is that of a young immunocompromised male with shortness of breath, as the pleural cavity is most commonly affected. Diagnosis is primarily based on fluid cytology in which PEL cells display variable morphology and a null lymphocyte immunophenotype; however, evidence of HHV-8 infection within the neoplastic cell is essential. Patients have commonly been treated with systemic multidrug chemotherapy and antiretroviral therapy if they were HIV positive or were immunocompromised for other reasons. In the immunocompetent patient, there have been no agreed-upon pathways for management of this condition. Progression of disease is common and median survival is approximately 6 months. Novel intrapleural treatments with antiviral agents such as intracavity cidofovir have shown to be effective in controlling local disease, and ongoing clinical trials may provide some promise in the treatment for this condition.

Non-small cell lung carcinoma spheroid models in agarose microwells for drug response studies.

There is a growing interest in developing personalized treatment strategies for each cancer patient, especially those with non-small cell lung carcinoma (NSCLC) which annually accounts for the majority of cancer related deaths in the US. Yet identifying the optimal NSCLC treatment strategy for each cancer patient is critical due to a multitude of mutations, some of which develop following initial therapy and can result in drug resistance. A key difficulty in developing personalized therapies in NSCLC is the lack of clinically relevant assay systems that are suitable to evaluate drug sensitivity using a minuscule amount of patient-derived material available following biopsies. Herein we leverage 3D printing to demonstrate a platform based on miniature microwells in agarose to culture cancer cell spheroids. The agarose wells were shaped by 3D printing molds with 1000 microwells with a U-shaped bottom. Three NSCLC cell lines (HCC4006, H1975 and A549) were used to demonstrate size uniformity, spheroid viability, biomarker expressions and drug response in 3D agarose microwells. Results show that our approach yielded spheroids of uniform size (coefficient of variation <22%) and high viability (>83% after 1 week-culture). Studies using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) drugs gefitinib and osimertinib showed clinically relevant responses. Based on the physical features, cell phenotypes, and responses to therapy of our spheroid models, we conclude that our platform is suitable for in vitro culture and drug evaluation, especially in cases when tumor sample is limited.

Current outcomes of simultaneous carotid endarterectomy and coronary artery bypass graft surgery in North America.

OBJECTIVE: Management of patients with concomitant carotid and coronary artery disease has been controversial. Divergent strategies have been employed, including simultaneous carotid endarterectomy and coronary bypass (SCC) versus various staged procedures. Although no strict comparison group is available, this study defines current outcomes of SCC, compared qualitatively to two reference categories. METHODS: Utilizing the STS database from 2003 to 2007, patients who had SCC were compared with patients with cerebrovascular disease who had coronary bypass (CABG) with prior carotid endarterectomy (CEA), and those with carotid Doppler stenosis >75% and no carotid intervention. Logistic regression analysis adjusted for differences in baseline characteristics and operative mortality (OM), and a composite of neurological complications (NC) was assessed. RESULTS: Of 745,769 patients who underwent isolated CABG with/without CEA, 108,212 (14%) had cerebrovascular disease. Of this group, 5,732 (5%) underwent SCC. The SCC group had more males and lower preoperative risk factors. After statistical adjustment for all baseline differences, SCC had clinically and statistically higher OM and NC compared with any of the reference groups, with 20-40% higher event risk. CONCLUSIONS: Although no quantitative control group exists for comparison, SCC as recently performed in North America has a high risk compared with any of the reference groups. Suboptimal results associated with the SCC strategy suggest a need for quality improvement and research on the optimal management of patients with simultaneous carotid and coronary disease.

Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non-Small Cell Lung Cancer.

PURPOSE: Low-dose CT screening can reduce lung cancer-related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation-based detection of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: This nested case-control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 27) had a noncancer diagnosis. We detected promoter methylation in plasma and urine samples using methylation on beads and quantitative methylation-specific real-time PCR for cancer-specific genes (CDO1, TAC1, HOXA7, HOXA9, SOX17, and ZFP42). RESULTS: DNA methylation at cancer-specific loci was detected in both plasma and urine, and was more frequent in patients with cancer compared with controls for all six genes in plasma and in CDO1, TAC1, HOXA9, and SOX17 in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and CDO1, TAC1, HOXA9, and SOX17 in urine were significantly associated with the diagnosis of NSCLC, independent of age, race, and smoking pack-years. When methylation was detected for three or more genes in both plasma and urine, the sensitivity and specificity for lung cancer diagnosis were 73% and 92%, respectively. CONCLUSIONS: DNA methylation-based biomarkers in plasma and urine could be useful as an adjunct to CT screening to guide decision-making regarding further invasive procedures in patients with pulmonary nodules.

Endovascular treatment of aortic aneurysms: techniques and clinical update.

Open repair of abdominal and thoracic aortic aneurysms continues to be associated with considerable morbidity and mortality. Endovascular repair of abdominal and thoracic aortic aneurysms has evolved over the past few years and has significantly reduced the morbidity of aortic aneurysm repair compared with the standard open surgical procedures. Several devices have been approved for clinical use for this purpose. This has allowed the treatment of patients who are otherwise at high risk for open repair. This review paper aims to (1) describe the general principles of use for endovascular devices and review the radiographic features and clinical trials for the devices in current use, (2) present the results of the clinical trials that led to the approval and marketing of the current devices, and (3) review new techniques and approaches for the treatment of aortic aneurysms.

Left Atrial and Carotid Body Paraganglioma.

We report a rare case of left atrial paraganglioma with a synchronous carotid body paraganglioma in a 30-year-old man with succinate dehydrogenase B gene mutation. The patient initially presented with a neck mass and palpitations. Laboratory test results showed elevated catecholamine levels. A cardiac paraganglioma was identified by computed tomography, meta-iodobenzylguanidine scintigraphy, and magnetic resonance imaging. Surgical resection of both paragangliomas were performed on two separate occasions. Serum and urine catecholamine levels returned to normal range. On follow-up, there was no recurrence of the cardiac paraganglioma. Radiotherapy was subsequently initiated for recurrence in the carotid body paraganglioma.

Primary Pulmonary Vein Leiomyosarcoma With Left Atrial Extension.

Leiomyosarcoma (LMS) is a mesenchymal tumor originating from the smooth muscle cells. LMS of the great vessels accounts for 60% of cases, with inferior vena cava being the most common site. Pulmonary vein LMS is an extremely rare subset that was first reported in 1939. LMS is an aggressive tumor, making surgical resection the treatment of choice. Herein, we present a rare case of pulmonary vein LMS extending into the left atrium, which was resected.

Outcome of coronary artery bypass operations in patients with renal insufficiency with and without renal transplantation.

HYPOTHESIS: Renal insufficiency (RI) is associated with an increased risk of morbidity and mortality following coronary artery bypass graft (CABG) operations, particularly among patients who are dependent on dialysis. DESIGN AND SETTING: A retrospective analysis of data collected at a tertiary care center. PATIENTS: One hundred eighty-four consecutive patients with RI who underwent CABG surgery between 1992 and 2004. This group consisted of 152 patients with serum creatinine levels of > or = 1.7 mg/dL (group I) and 32 kidney transplant recipients (group II). Of the patients in group I, 90 were dialysis-free (subgroup IA) and 62 were dialysis-dependent (subgroup IB). MAIN OUTCOME MEASURES: Demographics, perioperative data, and outcomes for each of the three groups were evaluated and compared. RESULTS: Fifty-four percent of the patients were in New York Heart Association classes III and IV, 36% had unstable angina, and 21% had left main coronary disease. The mean ejection fraction was 38%. The median postoperative length of stay in the hospital was 10 days. Of the patients in group IB, 8% required reexploration for bleeding compared to 3% in groups IA and II (p < 0.05). Dialysis was needed postoperatively in five patients in group IA and two patients in group II (5.7%). The raw operative mortality rate was 7.6% and was higher in group IB (9.7%) compared to groups IA and II (6.7% and 6.2%, respectively; p < 0.05). The actuarial 5-year survival rate was higher in group II compared to group I (79% vs 59%, respectively; p < 0.05). The difference in survival rates was more apparent between groups II and IB (79% vs 57%, respectively; p < 0.005). CONCLUSIONS: CABG is associated with an increased rate of perioperative complications and mortality in patients with RI. Dialysis dependence is a major risk factor for patients undergoing CABG surgery. However, with acceptable surgical results, dialysis patients should not be denied CABG surgery. A survival advantage is demonstrated among patients with previous kidney transplants compared to those patients who are dependent on dialysis.

Use of recombinant activated factor VII for bleeding following operations requiring cardiopulmonary bypass.

Postoperative bleeding is a common complication following cardiothoracic surgical procedures requiring cardiopulmonary bypass (CPB). Serious bleeding complications requiring the administration of blood products, hemostatic drugs, and even repeat surgery are associated with considerable morbidity, mortality, and resource consumption. Therapy with recombinant activated factor VII (rFVIIa) may be an effective treatment strategy for patients with refractory bleeding. We report the successful use of rFVIIa for the treatment of intractable postoperative bleeding following aortic aneurysm repair in two patients with Marfan syndrome. In both patients, surgical reexploration was avoided, and the patients' clinical status was stabilized after the administration of rFVIIa. In one patient, hemostasis was rapidly achieved within minutes, whereas hemostasis occurred gradually over several hours in the second patient. Including our personal experience with the two cases, the use of rFVIIa has been reported in 20 patients who required CPB for cardiothoracic surgical procedures. Hemostasis was achieved in all patients. In 14 patients (70%), rapid hemostasis was achieved following a single dose of rFVIIa (mean dose, 57 microg/kg). In the remaining six patients, gradual hemostasis was achieved after a mean of 3.4 doses (mean cumulative dose, 225 microg/kg). Two patients (10%) were believed to have experienced thromboembolic complications after the administration of rFVIIa (one was fatal), and, in another patient, intracoronary thrombosis was suspected but was not confirmed. In patients experiencing postoperative bleeding complications that are refractory to treatment with blood products, hemostatic agents, and/or repeat surgery, the use of rFVIIa may be considered.

Cardiac transplantation in patients with iron overload cardiomyopathy.

A review of the published world experience with heart transplantation for iron overload cardiomyopathy (IOC) between 1967 and 2003 as well as review of unpublished cases from the database of the United Network for Organ Sharing since 1992, identified a total of 16 patients (14 men and 2 women). Mean age was 31 years (range, 14-63 years). IOC etiology was hemochromatosis in 11 patients (69%), thalassemia major in 4 (25%), and Diamond-Blackfan anemia in 1 (6%). The 30-day mortality was 12%. Three patients (19%) died within 1 year of the transplant, all of infectious complications. An additional patient died at 7.14 years (unknown cause). The actuarial Kaplan-Meier 1-, 3-, and 5-year survival rates were 81% for all 3 time intervals. The actuarial 10-year survival was 41%.

Upper gastrointestinal bleeding caused by a "hypophrenic" diverticulum of the distal esophagus.

Distal esophageal diverticula are uncommon acquired anomalies of the distal thoracic esophagus. We report a case of an elderly man presenting with a history of upper gastrointestinal bleeding secondary to a distal esophageal diverticulum arising from the intra-abdominal portion of the esophagus. To our knowledge, this is the first report of upper gastrointestinal bleeding from a subdiaphragmatic esophageal diverticulum. We propose the term "hypophrenic diverticulum of the esophagus" for this disease entity, and we would like to bring it to the attention of readers of The American Surgeon.

Primary neuroendocrine tumors of the thymus.

Primary neuroendocrine tumors of the thymus are highly aggressive tumors that rarely occur. A little more than 200 cases have been reported, many of which were single case reports. Only a few articles contained modest series from single centers for analysis. A review of 157 cases collected from the major series reported to-date show a clinical pattern with male preponderance (male:female ratio, 3:1) and a mean age of 54 years. Most patients presented with symptoms and signs of local compression. Almost 50% of these tumors were functionally active and were associated with endocrinopathies. Several histologic variants have been described, all with similar ultrastructural features. The biologic behavior of these tumors shows a direct relation to the degree of differentiation. Whenever possible, surgical resection is the treatment of choice as adjuvant therapy is controversial and has been used with variable success. Potential therapies exploit the presence of somatostatin receptors on a variety of these tumors. Use of radiolabeled Octreotide for radionuclide therapy has yielded tumor inhibition in animal models and may have clinical application. Fifty-one percent of the patients survived 3 years, 27% survived 5 years, and less than 10% survived beyond 10 years. Histologic grade, tumor extension, and early detection are the most important factors affecting survival. Other prognostic factors that impact outcome include presence of endocrinopathy, incomplete resectability, nodal status, and presence of distant metastasis.