High-intensity statin treatment is associated with reduced plaque structural stress and remodelling of artery geometry and plaque architecture.

Aims: Plaque structural stress (PSS) is a major cause of atherosclerotic plaque rupture and major adverse cardiovascular events (MACE). We examined the predictors of changes in peak and mean PSS (ΔPSSpeak, ΔPSSmean) in three studies of patients receiving either standard medical or high-intensity statin (HIS) treatment. Methods and results: We examined changes in PSS, plaque size, and composition between 7348 co-registered baseline and follow-up virtual-histology intravascular ultrasound images in patients receiving standard medical treatment (controls, n = 18) or HIS (atorvastatin 80 mg, n = 20, or rosuvastatin 40 mg, n = 22). The relationship between changes in PSSpeak and plaque burden (PB) differed significantly between HIS and control groups (P < 0.001). Notably, PSSpeak increased significantly in control lesions with PB >60% (P = 0.04), but not with HIS treatment. However, ΔPSSpeak correlated poorly with changes in lumen and plaque area or PB, plaque composition, or lipid lowering. In contrast, ΔPSSpeak correlated significantly with changes in lumen curvature, irregularity, and roughness (P < 0.05), all of which were reduced in HIS patients. ΔPSSmean correlated with changes in lumen area, PA, PB, and circumferential calcification, and was unchanged with either treatment. Conclusion: Our observational study shows that PSSpeak changes over time were associated with baseline disease severity and treatment. The PSSpeak increase seen in advanced lesions with standard treatment was associated with remodelling artery geometry and plaque architecture, but this was not seen after HIS treatment. Smoothing plaques by reducing plaque/lumen roughness, irregularity, and curvature represents a novel mechanism whereby HIS may reduce PSS and, thus may protect against plaque rupture and MACE.

Superficial and multiple calcifications and ulceration associate with intraplaque hemorrhage in the carotid atherosclerotic plaque.

OBJECTIVE: Intraplaque hemorrhage (IPH) and ulceration of carotid atherosclerotic plaques have been associated with vulnerability while calcification has been conventionally thought protective. However, studies suggested calcification size and location may increase plaque vulnerability. This study explored the association between calcium configurations and ulceration with IPH. METHODS: One hundred thirty-seven consecutive symptomatic patients scheduled for carotid endarterectomy were recruited. CTA and CTP were performed prior to surgery. Plaque samples were collected for histology. According to the location, calcifications were categorized into superficial, deep and mixed types; according to the size and number, calcifications were classified as thick and thin, multiple and single. RESULTS: Seventy-one plaques had IPH (51.8%) and 83 had ulceration (60.6%). The appearance of IPH and ulceration was correlated (r = 0.49; p < 0.001). The incidence of multiple, superficial and thin calcifications was significantly higher in lesions with IPH and ulceration compared with those without. After adjusting factors including age, stenosis and ulceration, the presence of calcification [OR (95% CI), 3.0 (1.1-8.2), p = 0.035], multiple calcification [3.9 (1.4-10.9), p = 0.009] and superficial calcification [3.4 (1.1-10.8), p = 0.001] were all associated with IPH. ROC analysis showed that the AUC of superficial and multiple calcifications in detecting IPH was 0.63 and 0.66, respectively (p < 0.05). When the ulceration was combined, AUC increased significantly to 0.82 and 0.83, respectively. Results also showed that patients with lesions of both ulceration and IPH have significantly reduced brain perfusion in the area ipsilateral to the infarction. CONCLUSIONS: Superficial and multiple calcifications and ulceration were associated with carotid IPH, and they may be a surrogate for higher risk lesions. KEY POINTS: • CTA-defined superficial and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of intraplaque hemorrhage. • The combination of superficial and multiple calcifications and ulceration is highly predictive of carotid intraplaque hemorrhage. • Patients with lesions of both ulceration and intraplaque hemorrhage have significantly reduced brain perfusion in the area ipsilateral to the infarction.

RhoC interacts with integrin α5ß1 and enhances its trafficking in migrating pancreatic carcinoma cells.

Human pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic dissemination. Although RhoC has been implicated in cancer cell migration, the relevant underlying molecular mechanisms remain unknown. RhoC has been implicated in the enhancement of cancer cell migration and invasion, with actions which are distinct from RhoA (84% homology), and are possibly attributed to the divergent C-terminus domain. Here, we confirm that RhoC significantly enhances the migratory and invasive properties of pancreatic carcinoma cells. In addition, we show that RhoC over-expression decreases cancer cell adhesion and, in turn, accelerates cellular body movement and focal adhesion turnover, especially, on fibronectin-coated surfaces. Whilst RhoC over-expression did not alter integrin expression patterns, we show that it enhanced integrin α5ß1 internalization and re-cycling (trafficking), an effect that was dependent specifically on the C-terminus (180-193 amino acids) of RhoC protein. We also report that RhoC and integrin α5ß1 co-localize within the peri-nuclear region of pancreatic tumor cells, and by masking the CAAX motif at the C-terminal of RhoC protein, we were able to abolish this interaction in vitro and in vivo. Co-localization of integrin α5ß1 and RhoC was demonstrable in invading cancer cells in 3D-organotypic cultures, and further mimicked in vivo analyses of, spontaneous human, (two distinct sources: operated patients and rapid autopsy programme) and transgenic murine (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), pancreatic cancers. In both cases, co-localization of integrin α5ß1 and RhoC correlated with poor differentiation status and metastatic potential. We propose that RhoC facilitates tumor cell invasion and promotes subsequent metastasis, in part, by enhancing integrin α5ß1 trafficking. Thus, RhoC may serve as a biomarker and a therapeutic target.

Routine underwater seal drains are not required after transthoracic oesophagectomy: a pilot study.

OBJECTIVE: Underwater seal drainage of the pleural cavity has been standard practice after transthoracic oesophagectomy. However these chest tubes cause pain and hamper mobility, thereby causing significant morbidity and delaying recovery. We postulated that if complete lung expansion and optimum pulmonary function could be achieved and maintained following a transthoracic oesophagectomy using simple gravity aided transabdominal tube drainage of the pleural cavity, then these may be a simpler alternative to the conventional underwater seal chest drains. METHODS: A total of 50 patients had transthoracic oesophagectomy for oesophageal cancer. Of the cohort, 44 patients were fitted with the transabdominal drain described and hence had 'modified pleural drainage' following the oesophagectomy. All patients had a posterior mediastinal drain placed in either the right or the left pleural cavity during the oesophagectomy. The tube drain was inserted into the pleural cavity from the abdomen and placed into the desired position across the diaphragmatic hiatus. The drain was managed in the conventional manner and patients were monitored postoperatively for any developing pleural collections through serial chest X-rays. Respiratory function was closely monitored. RESULTS: The drains were removed without any significant respiratory complications by the 8th postoperative day in 86% of the patients. Only three patients (7%) developed clinically significant recurrent pleural effusions, causing respiratory compromise meriting further drainage. This was easily and safely managed using fine bore pigtail drains inserted under ultrasound guidance. CONCLUSION: Transabdominal gravity aided tube drainage of the mediastinum and the pleural cavity is an effective and safe means of draining the chest, following uncomplicated transthoracic oesophagectomy.

Biliary Cystadenoma Causing Obstructive Jaundice: Case Report and Literature Review.

Biliary cystadenomas are rare, potentially malignant neoplasms of biliary origin. Presentation is usually with vague and non-specific symptoms. Here, we describe an unusual case of biliary cystadenoma in a woman presenting with acute onset obstructive jaundice and review the relevant literature of 26 such cases reported over the last two decades.