Histological and immunohistochemical evaluation of human saphenous vein harvested by endoscopic and open conventional methods.

OBJECTIVES: The introduction of endoscopic saphenous vein harvesting (ESVH) has been reported to decrease saphenectomy-associated wound pain and infection, compared with the traditional open conventional saphenous vein harvesting (OCSVH) technique. Despite all these benefits, the rate of adoption among surgeons has been variable. Criticism of this technique centres on the risk of injury at the time of vein harvest with its potential detrimental effect on structural viability and long-term patency. The aim of our study is to investigate the endothelial preservation of saphenous vein grafts harvested by various extraction methods. METHODS: A prospective, observational study of 30 human saphenous vein grafts was performed to evaluate endothelial preservation by haematoxylin-eosin and CD 31 staining methods. The saphenous vein was harvested endoscopically either by an open tunnel (OT-ESVH), closed tunnel (CT-ESVH) or an OCSVH harvesting technique. Research samples were collected without distension to avoid intraluminal dilatation and endothelial disruption. Both haematoxylin-eosin and immunohistochemistry slides were imaged by a high-resolution slide-scanning system. RESULTS: Haematoxylin-eosin staining of the CT-ESVH group showed mostly preserved endothelium (P = 0.398) with some endothelial stretching (P = 1.0) and no endothelial detachment (P = 0.197). The OT-ESVH group showed marked endothelial stretching (P = 0.053). However, the OCSVH group showed significantly more endothelial detachment than the endoscopic groups (P = 0.01). The mean grading score of immunohistochemistry using the CD 31 antibody was much lower in the OT-ESVH group (1.6 ± 0.84, P = 0.009), showing more poorly preserved endothelial cells than the CT-ESVH and OCSVH groups. CONCLUSIONS: We observed more endothelial stretching in the OT-ESVH group, which in our opinion, was due to lack of subcutaneous tissue separation, poor visualization and traction stresses across the wall of the saphenous vein. However, the OCSVH method revealed poor endothelial protection with areas of endothelial detachment, not observed with both endoscopic techniques. Interestingly, most preserved endothelium was found in the CT-ESVH group, which was previously known to be associated with worse graft patency.

Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study.

BACKGROUND: Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation. METHODS: All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant. RESULTS: 88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (-12.7±2.5% vs. -13.7±3.6%, p=0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised. CONCLUSIONS: This study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR during the early phase post-transplantation.

Sarcoma-like tumor of head and neck skin.

A group of tumors referred to as atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) predominantly occur in sun-damaged skin of the elderly, particularly in the head and neck region. Although this group of tumors is often regarded as of mesenchymal phenotype, the matter of histogenesis has not been entirely resolved. Evans H and Smith JL reported in 1980 that prognosis was not significantly different irrespective of whether there was a definite squamous cell carcinoma component or not, supporting a view that these are all carcinomata in nature (sarcomatoid carcinoma [SC]). There are a number of clinicopathologic studies of AFX in the literature but information on morphologically similar sarcoma-like tumors with immunohistochemical evidence of epithelial differentiation is sparse. One hundred sarcoma-like tumors (SLTs) of head and neck skin of the elderly, treated by surgical excision, were studied. Clinical information was obtained, and pathology reports and hematoxylin and eosin sections were reviewed to document size (maximum dimension), extent of invasion, mitotic count, vascular and perineural invasion, margin status, ulceration, necrosis, and the presence of actinic keratosis in adjacent/overlying skin. Immunostains examined included: pan-cytokeratins (CKs) (AE1/AE3, MNF116), high-molecular weight CKs (34ßE12, CK5/6, CK14), p63, and melanocytic (S100, Melan A, HMB-45, MITF), vascular (CD31, CD34), and muscle markers (SMA, desmin, h-caldesmon) to exclude melanoma and definite sarcoma entities. The tumors were divided into AFX/PDS (G1), the SC group, which was subdivided into SLT with only p63 positivity (G2a) and SLT with CK positivity regardless of p63 status (G2b), and SLT with a minor morphologic squamous cell carcinoma component (G3). Clinicopathologic findings of each group were compared, in relation to outcomes. Age at diagnosis ranged from 51 to 96 years (median, 79 y), with M:F=11.5:1. There were 53 tumors in G1 (19AFX, 34PDS), 37 in G2 (25 in G2a, 12 in G2b), and 10 in G3. There was no statistically significant difference in clinical and pathologic parameters or survival among all 3 groups. CKs and p63 expression, size, extent of invasion, vascular invasion, perineural invasion, mitotic count, and ulcer did not affect outcome, whereas margin status and necrosis did by both univariate and multivariate analysis and by only univariate analysis, respectively. Sixty patients had multiple nonmelanomatous skin cancers. Actinic keratosis was observed in overlying/adjacent epidermis in 51 cases. Eight patients had prior radiotherapy to head skin cancers; 1 patient developed 2 separate tumors (G1 and G3) after radiotherapy. Four patients died of tumor (1 G1, 2 G2b, and 1 G3); of these, 3 cases had positive margin, and 1 had narrow margin. Our results have shown similarities of various clinicopathologic parameters between AFX/PDS and SC, raising the possibility that both entities are related, and some of the former entities may represent complete dedifferentiation (complete loss of epithelial phenotype) with a gain of mesenchymal phenotype. In addition, the difference between AFX and PDS appears to be the extent of invasiveness (stage) rather than a different histogenesis. Further investigations are needed. However, from a practical point of view, efforts should be made to excise this group of tumors with clear margins, as margin status appears to be the most important prognostic factor regardless of the presence or absence of epithelial differentiation.

Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer.

PURPOSE: The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use. EXPERIMENTAL DESIGN: AZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray (TMA) from 78 patients with SCLC. RESULTS: AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors. CONCLUSIONS: This study provides a rationale to test AZD3965 in patients with SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond.

PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study.

BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207.

An unusual presentation of anti-Jo-1 syndrome, mimicking lung metastases, with massive pleural and pericardial effusions.

We report a case of anti-Jo-1 syndrome (a rare autoimmune condition that may manifest with various forms of interstitial lung disease), which in our case presented unusually with multiple pulmonary nodules, mimicking carcinoma. She subsequently developed pleural and pericardial effusions (which are rare in this syndrome), myopathy, and "mechanic's hand," with similar lesions on the feet. "Mechanic's foot" noted in this patient has not been previously described. She initially responded well to immunosuppression but has subsequently progressed to pulmonary fibrosis.