Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery

Background: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. Patients and methods: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. Results: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. Conclusion: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcom

Direct and inverse pumping in flows with homogeneous and non-homogeneous swirl

The conditions in which meridional recirculations appear in swirling flows above a fixed wall are analysed. In the classical Bodew\"adt problem, where the swirl tends towards an aysmptotic value away from the wall, the well-known "tea-cup effect" drives a flow away from the plate at the centre of the vortex. Simple dimensional arguments applied to a single vortex show that if the intensity of the swirl decreases away from the wall, the sense of the recirculation can be inverted, and that the associated flow rate scales with the swirl gradient. Only if the flow is quasi-2D, does the classical tea-cup effect take place. This basic theory is confirmed by numerical simulations of a square array of steady, electrically driven vortices. Experiments in the turbulent regimes of the same configuration reveal that these mechanisms are active in the average flow and in its fluctuating part. The mechanisms singled out in this letter provide an explanation for previously observed phenomena in electrolyte flows. They also put forward a possible mechanism for the generation of helicity in flows close to two-dimensionality, which plays a key role in the transition between 2D and 3D turbulence

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer

Background: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. Patients and methods: A large series of surgically resected liver metastases (n = 153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (α-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. Results: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. Conclusions: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplati

Limitation of the excessive extracellular matrix turnover is a major determinant of the beneficial effect of spironolactone on survival in patients with CHF: Insights from the RALES trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106131/1/ejhf80350-5.pd

Extrahepatic Portal Hypertension following Liver Transplantation: a Rare but Challenging Problem

This study reports our experience of 8 cases of extrahepatic portal hypertension after 273 orthotopic liver transplantations in 244 adult patients over a 10- year period. The main clinical feature was ascites, and the life-threatening complication was variceal bleeding. Extrahepatic portal hypertension was caused by portal vein stenosis in 6 patients, and left-sided portal hypertension in 2 patients after inadventent ligation of portal venous tributaries or portasystemic shunts. All patients with portal vein stenosis had complete relief of portal hypertension after percutaneous transhepatic venoplasty (n=4) or surgical reconstruction (n=2), after a median follow-up of 33 (range: 6–62) months. Of the 2 patients with left-sided portal hypertension, one died after splenectomy and one rebled 6 months after left colectomy. This study suggests that extrahepatic portal hypertension is a series complication after liver transplantation that could be prevented by meticulous portal anastomosis and closure of portal tributaries or portasystemic shunts to improve the portal venous flow. However, any ligation has to be performed under ultrasound guidance to avoid inadventent venous ligations

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

"Cowboy Cloth" and kinship: The closeness of denim consumption in a south-west Chinese city

This article examines the effect of the fabric denim in objectifying kinship in the city of Kunming, China. It is argued that denim has been particularly efficacious due to its ability to insert itself into traditional Chinese kinship notions of nurturance. Parents were seen to gift denim to their children with the object of instigating a change in the lives of the younger generation, coupled with the knowledge that a change in material circumstances would be necessary to achieve such transformation. At the same time, the younger generation's denim also provoked a "kinship gulf" between children and their parents, which parents appeared keen to close by purchasing and wearing denim of their own (although not without a degree of ambivalence, reflected by the presence of inactive jeans in parents' wardrobes). In this remarkable situation denim was seen, firstly, as the tool for creating generational disjuncture through traditional means and subsequently as the prospective solution to overcome this disjuncture. It is argued here that denim moves us to consider the study of kinship as the study of "closeness," a term that affords the consideration of objects in the milieu of intimate social relationships. © 2011 Berg. Printed in the United Kingdom

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin

The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated