Stacey A. Carter

Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

Background A 24-year-old man presented with previously diagnosed Marfans syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment.Investigations CT scans, arteriogram, genetic mutation screening of transforming growth factor β receptors 1 and 2.Diagnosis Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfans syndrome, but was later rediagnosed with Loeys–Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor β receptor 2.Management Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease.

Increased Collagen Deposition and Elevated Expression of Connective Tissue Growth Factor in Human Thoracic Aortic Dissection

Background— Thoracic aortic dissection (TAD) is characterized by dysregulated extracellular matrix. Little is known about the alterations of collagen and stimulators of collagen synthesis, eg, connective tissue growth factor (CTGF), in patients with TAD. In this study, we examined their roles in TAD. Methods and Results— Surgical specimens of the aortic wall of TAD patients (n=10) and controls (n=10) were tested for collagen types I and III and CTGF expression. When compared with controls, protein levels of type I and III collagen and CTGF were significantly increased by 3.2-, 3.7-, and 5.3-fold, respectively (P<0.05 for all). Similar patterns were shown in mRNA levels of type I&agr; and I&agr;2 collagen and CTGF. Using immunohistochemistry and trichrome staining, we also observed elevated levels of collagen in the aortic media and adventitia. Treatment with recombinant human CTGF increased collagen synthesis in cultured aortic smooth muscle cells in a dose- and time-dependent fashion, in which expression of collagens increased from 506±108 counts per minute to 2764±240 cpm by 50 ng/mL CTGF, and from 30±43 cpm to 429±102 cpm at 48 hours. Conclusions— TAD patients exhibited significantly increased expression of aortic collagen types I and III as well as CTGF, which is likely to be responsible for the compromised aortic distensibility and systemic compliance. Because CTGF can increase collagen expression, CTGF may be a new target molecule in the pathogenesis and progression of TAD.

Organ protection during thoracoabdominal aortic surgery: rationale for a multimodality approach.

Surgical repair of thoracoabdominal aortic aneurysms (TAAAs) remains a technically challenging operation that requires a systematic approach to prevent ischemic complications and achieve excellent clinical outcomes. Techniques for organ protection have evolved substantially over the past 20 years. This review describes our current multimodality approach to organ protection during TAAA repair.

Axillary Artery Cannulation in Surgery for Acute or Subacute Ascending Aortic Dissections

BACKGROUND Perfusion through the right axillary artery is an alternative to aortic or femoral artery cannulation during surgery for ascending aortic dissections. The results of this strategy, particularly beyond the immediate postoperative period, are not well described. METHODS Eighty-three patients (median age, 58 years) with acute or subacute ascending aortic dissection underwent surgical repair with right axillary artery perfusion through an interposition Dacron graft. Sixty-five patients (78%) had DeBakey type I dissections. Procedures performed concomitantly with ascending aortic replacement included root replacement (n = 16; 19%), aortic valve repair or replacement (n = 51; 61%), and coronary artery bypass grafting (n = 13; 16%). Hypothermic circulatory arrest with antegrade cerebral perfusion was used in the majority of patients (n = 60; 72%). We retrospectively studied short-term and midterm outcomes, including survival and complications relating to the axillary cannulation. RESULTS No patient incurred intraoperative axillary artery injuries or had arm ischemia. Fourteen patients (17%) died in the hospital or within 30 days of surgery, and 9 patients (11%) had strokes. Actuarial survival was 73% +/- 5% at 1 year and 64% +/- 6% at 3 years. Forty-six of the 57 surviving patients could be contacted by telephone; they reported few late complications related to the axillary artery cannulation site. These complications included 1 case each of right-arm weakness and right-arm numbness. CONCLUSIONS Surgical repair of acute aortic dissection with right axillary artery perfusion can be performed safely, with a relatively low risk of stroke and a high probability of midterm survival.

Identifying Risk Factors for Surgical Site Complications after Laparoscopic Ventral Hernia Repair: Evaluation of the Ventral Hernia Working Group Grading System

BACKGROUND In 2010, the Ventral Hernia Working Group (VHWG) published a grading system to assess the risk of surgical site complications in patients undergoing ventral hernia repair. This study evaluated the predictive value of the VHWG classification for the surgical outcomes of laparoscopic ventral hernia repair (LVHR) and identified independent factors associated with surgical site infection (SSI) and surgical site occurrence (SSO). METHODS A retrospective review was performed of all patients who underwent LVHR over a 10-year period at two institutions. The U.S. Centers for Disease Control and Prevention definition of SSI and the VHWG definition of SSO were used. Univariable analysis was performed using the Student t-test, analysis of variance, chi-square test, or Fisher exact test, as appropriate. Multivariable analysis was used to identify independent factors associated with SSI and SSO. RESULTS Differences in American Society of Anesthesiologists class, body mass index, diabetes mellitus, chronic obstructive pulmonary disease, tobacco use, hernia type, prior abdominal surgery, prior ventral hernia repair, hernia size, and total infections were identified by grade. There was no difference in SSI or SSO by grade. Multivariable analysis revealed institution and number of prior abdominal operations to be associated with SSI. Institution, prostate disease, and prior ventral hernia repair were associated with SSO. CONCLUSIONS The VHWG classification was unable to predict SSI and SSO and may not be applicable in LVHR. This study identified independent factors associated with SSI and SSO in LVHR. Although further study is warranted to validate these results, the factors presented may be a useful tool to stratify patient risk of SSI and SSO with LVHR.

Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

AbstractAmbient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. Graphical AbstractDesorption electrospray ionization mass spectrometry imaging is used to differentiate metastatic cancer from adjacent lymph node tissue

Multicenter Study Using Desorption-Electrospray-Ionization-Mass-Spectrometry Imaging for Breast-Cancer Diagnosis

The histological and molecular subtypes of breast cancer demand distinct therapeutic approaches. Invasive ductal carcinoma (IDC) is subtyped according to estrogen-receptor (ER), progesterone-receptor (PR), and HER2 status, among other markers. Desorption-electrospray-ionization-mass-spectrometry imaging (DESI-MSI) is an ambient-ionization MS technique that has been previously used to diagnose IDC. Aiming to investigate the robustness of ambient-ionization MS for IDC diagnosis and subtyping over diverse patient populations and interlaboratory use, we report a multicenter study using DESI-MSI to analyze samples from 103 patients independently analyzed in the United States and Brazil. The lipid profiles of IDC and normal breast tissues were consistent across different patient races and were unrelated to country of sample collection. Similar experimental parameters used in both laboratories yielded consistent mass-spectral data in mass-to-charge ratios ( m/ z) above 700, where complex lipids are observed. Statistical classifiers built using data acquired in the United States yielded 97.6% sensitivity, 96.7% specificity, and 97.6% accuracy for cancer diagnosis. Equivalent performance was observed for the intralaboratory validation set (99.2% accuracy) and, most remarkably, for the interlaboratory validation set independently acquired in Brazil (95.3% accuracy). Separate classification models built for ER and PR statuses as well as the status of their combined hormone receptor (HR) provided predictive accuracies (>89.0%), although low classification accuracies were achieved for HER2 status. Altogether, our multicenter study demonstrates that DESI-MSI is a robust and reproducible technology for rapid breast-cancer-tissue diagnosis and therefore is of value for clinical use.