No abstract

The implementation of a surgical safety checklist is said to minimize postoperative surgical complications. However, to our knowledge, no randomized controlled study has been done on the influence of checklists on postoperative outcomes in a developing country. We conducted a prospective randomized controlled study with parallel group study design of the implementation of WHO surgical safety checklist involving 700 consecutive patients undergoing operations in our hospital between February 2012 and April 2013. In 350 patients, the checklist was implemented with modifications-the Rc arm. The control group of 350 patients was termed the Rn arm. The checklist was filled in by a surgery resident, and only the participants in the study were blinded. Postoperative wound-related (p = 0.04), abdominal (p = 0.01), and bleeding (p = 0.03) complications were significantly lower in the Rc compared to the Rn group. The number of overall and higher-grade complications (Clavien-Dindo grades 3 and 4) per patient reduced from 0.97 and 0.33 in the Rn arm to 0.80 and 0.23 in the Rc arm, respectively. A significant reduction in mortality was noted in the Rc arm as compared to the Rn arm (p = 0.04). In a subgroup analysis, the number of overall and higher-grade complications per patient with incomplete checklists was higher than that with fully completed checklist group. Implementation of WHO surgical safety checklist results in a reduction in mortality as well as improved postoperative outcomes in a tertiary care hospital in a developing country.

Context.-The common risk factors for hepatocellular carcinoma (HCC) include persistent viral infection with either hepatitis B or C virus, alcohol abuse, hemochromatosis, and metabolic syndrome. Steatohepatitic (SH) HCC has been recently recognized as a special morphologic variant of HCC associated with metabolic risk factors.Objective.-To assess the SH pattern in HCC cases of various etiologies in Indian patients and to further correlate this morphology with the presence of metabolic risk factors.Design.-A total of 101 cases of HCC with various etiologies in explanted livers from adults were included in the study. Morphologic examination was performed to identify SH lesions within the tumor and in the nontumorous liver parenchyma. Correlation of nontumor and tumor SH morphology with clinically identifiable metabolic risk factors and with non-SH type of HCC was performed.Results.-The SH variant of HCC was identified in 19 livers (18.8%). Most SH-HCC cases were associated with metabolic risk factors such as obesity, diabetes, hypertension, and hyperlipidemias. Comparison of SH-HCC with non-SH-HCC was statistically significant in terms of presence of metabolic risk factors.Conclusions.-Steatohepatitic morphology in HCC is frequent in nonalcoholic fatty liver disease-associated cirrhosis (P ¼ .009) and is significantly associated with metabolic risk factors (P ¼ .03). By recognizing SH pattern, one may predict associated metabolic diseases and determine the prognosis both in pretransplant and posttransplant patients. (Arch Pathol Lab Med. 2013;137:961-966; doi: 10.5858/ arpa.2012-0048-OA) H epatocellular carcinoma (HCC) accounts for 85% to 90% of all primary liver cancers.1 There is wide geographic variation of prevalence of HCC, with Asia and Africa having 40 times more cases than other parts of the world.2 However, the incidence of HCC has been rising throughout the world, with particularly large increases seen in industrialized nations such as the United States and Denmark.3 Nonalcoholic fatty liver disease (NAFLD) ranges in severity from steatosis to steatohepatitis (NASH, nonalcoholic steatohepatitis) and finally to cirrhosis, which is known to be a risk factor for the development of HCC. 4 In Western and Asian countries, the prevalence of NAFLD in the general population is increasing dramatically.5 Genetic factors may in part contribute to the rise in NAFLD. Polymorphisms within various genes have been linked to NAFLD in lean Indian men.6 Emerging evidence has established multiple independent risk factors for the development of HCC in NAFLD, which include obesity, diabetes, and iron deposition. 7,8 Recently a new morphologic variant of HCC named steatohepatitic hepatocellular carcinoma has been identified that relates to the presence of metabolic syndrome.9,10 The aim of the study is to recognize steatohepatitic (SH) pattern in HCC cases of various etiologies in Indian patients and to further correlate this variant with the presence of metabolic risk factors. MATERIALS AND METHODSBetween January 2004 and ...

Summary.  Background: The deficiency of factor VIII, a co‐factor in the intrinsic coagulation pathway results in hemophilia A. Although FVIII is synthesized largely in the liver, the specific liver cell type(s) responsible for FVIII production is controversial. Objective: This study aimed to determine the cellular origin of FVIII synthesis and release in mouse models. Methods: We transplanted cells into the peritoneal cavity of hemophilia A knockout mice. Plasma FVIII activity was measured using a Chromogenix assay 2–7 days after cell transplantation, and phenotypic correction was determined with tail‐clip challenge 7 days following cell transplantation. Transplanted cells were identified by histologic and molecular assays. Results: Untreated hemophilia A mice, as well as mice treated with the hepatocyte‐enriched fraction, showed extensive mortality following tail‐clip challenge. In contrast, recipients of unfractionated liver cells (mixture of hepatocytes, liver sinusoidal endothelial cells (LSEC), Kupffer cells, and hepatic stellate cells) or of the cell fraction enriched in LSECs survived tail‐clip challenge (P < 0.001). FVIII was secreted in the blood stream in recipients of unfractionated liver cells, LSECs and pancreatic islet‐derived MILE SVEN 1 (MS1) endothelial cells. Although transplanted hepatocytes maintained functional integrity in the peritoneal cavity, these cells did not produce detectable plasma FVIII activity. Conclusions: The assay of cell transplantation in the peritoneal cavity showed that endothelial cells but not hepatocytes produced phenotypic correction in hemophilia A mice. Therefore, endothelial cells should be suitable additional targets for cell and gene therapy in hemophilia A.

The potential for organ damage after using drugs or chemicals is a critical issue in medicine. To delineate mechanisms of drug-induced hepatic injury, we used transplanted cells as reporters in dipeptidyl peptidase IV-deficient mice. These mice were given phenytoin and rifampicin for 3 days, after which monocrotaline was given followed 1 day later by intrasplenic transplantation of healthy C57BL/6 mouse hepatocytes. We examined endothelial and hepatic damage by serologic or tissue studies and assessed changes in transplanted cell engraftment and liver repopulation by histochemical staining for dipeptidyl peptidase IV. Monocrotaline caused denudation of the hepatic sinusoidal endothelium and increased serum hyaluronic acid levels, along with superior transplanted cell engraftment. Together, phenytoin, rifampicin, and monocrotaline caused further endothelial damage, reflected by greater improvement in cell engraftment. Phenytoin, rifampicin, and monocrotaline produced injury in hepatocytes that was not apparent after conventional tissue studies. This led to transplanted cell proliferation and extensive liver repopulation over several weeks, which was more efficient in males compared with females, including greater induction by phenytoin and rifampicin of cytochrome P450 3A4 isoform that converts monocrotaline to toxic intermediates. Through this and other possible mechanisms, monocrotaline-induced injury in the endothelial compartment was retargeted to simultaneously involve hepatocytes over the long term. Moreover, after this hepatic injury, native liver cells were more susceptible to additional pro-oxidant injury through thyroid hormone, which accelerated the kinetics of liver repopulation. Conclusion: Transplanted reporter cells will be useful for obtaining insights into homeostatic mechanisms involving liver cell compartments, whereas targeted injury in hepatic endothelial and parenchymal cells with suitable drugs will also help advance liver cell therapy. ( T o obtain fresh paradigms in tissue homeostasis after exposure to drugs or chemicals, 1 we considered that reporter cells will help elucidate perturbations in the liver, because genetically marked reporter cells can be inserted into liver compartments, including the parenchyma or hepatic endothelium. 2-4 It was noteworthy that transplanted cells did not proliferate in the normal liver, where cell turnover is minimal, although, depending on the extent of injury in native cells, proliferation in healthy transplanted cells was activated. 5,6 In this way, transplanted cells could repopulate the liver, where in specific situations the kinetics of liver repopulation reflected loss of native hepatocytes. [7][8][9] In healthy animals, genotoxic manipulations were particularly effective in promoting such liver repopulation with healthy cells. However, further insights are necessary to obtain pharmacologic approaches for repopulating the liver, particularly for clinical applications.To develop cell compartment-specific hepatic perturbations, we used monocrotaline (...