Background Posthepatectomy liver failure is a feared complication after hepatic resection and a major cause of perioperative mortality. There is currently no standardized definition of ...posthepatectomy liver failure that allows valid comparison of results from different studies and institutions. The aim of the current article was to propose a definition and grading of severity of posthepatectomy liver failure. Methods A literature search on posthepatectomy liver failure after hepatic resection was conducted. Based on the normal course of biochemical liver function tests after hepatic resection, a simple and easily applicable definition of posthepatectomy liver failure was developed by the International Study Group of Liver Surgery. Furthermore, a grading of severity is proposed based on the impact on patients' clinical management. Results No uniform definition of posthepatectomy liver failure has been established in the literature addressing hepatic surgery. Considering the normal postoperative course of serum bilirubin concentration and International Normalized Ratio, we propose defining posthepatectomy liver failure as the impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased international normalized ratio and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5. The severity of posthepatectomy liver failure should be graded based on its impact on clinical management. Grade A posthepatectomy liver failure requires no change of the patient's clinical management. The clinical management of patients with grade B posthepatectomy liver failure deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C posthepatectomy liver failure. Conclusion The current definition of posthepatectomy liver failure is simple and easily applicable in clinical routine. This definition can be used in future studies to allow objective and accurate comparisons of operative interventions in the field of hepatic surgery.
Background Despite the potentially severe impact of bile leakage on patients’ perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic ...operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. Methods An international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients’ serum and drain fluid. Results After evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients’ clinical management. Grade A bile leakage causes no change in patients’ clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required. Conclusion We propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy.
Liver resection (LR) in patients with hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH) defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg is not ...encouraged. Here, we reappraised the outcomes of patients with cirrhosis and CSPH who underwent LR for HCC in highly specialised liver centres.
This was a retrospective multicentre study from 1999 to 2019. Predictors for postoperative liver decompensation and textbook outcomes were identified.
In total, 79 patients with a median age of 65 years were included. The Child-Pugh grade was A in 99% of patients, and the median model for end-stage liver disease (MELD) score was 8. The median HVPG was 12 mmHg. Major hepatectomies and laparoscopies were performed in 28% and 34% of patients, respectively. Ninety-day mortality and severe morbidity rates were 6% and 27%, respectively. Postoperative and persistent liver decompensation occurred in 35% and 10% of patients at 3 months. Predictors of liver decompensation included increased preoperative HVPG (p = 0.004), increased serum total bilirubin (p = 0.02), and open approach (p = 0.03). Of the patients, 34% achieved a textbook outcome, of which the laparoscopic approach was the sole predictor (p = 0.004). The 5-year overall survival and recurrence-free survival rates were 55% and 43%, respectively.
Patients with cirrhosis, HCC and HVPG ≥10 mmHg can undergo LR with acceptable mortality, morbidity, and liver decompensation rates. The laparoscopic approach was the sole predictor of a textbook outcome.
Patients with cirrhosis, hepatocellular carcinoma, and clinically significant portal hypertension (defined as a hepatic venous pressure gradient ≥10 mmHg) can undergo resection with acceptable mortality, morbidity, liver decompensation rates, and a textbook outcome. These results can be achieved in selected patients with preserved liver function, good general status, and sufficient remnant liver volume.
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•Patients with HCC and CSPH can undergo resection, with mortality of 6% and severe morbidity of 27%.•Postoperative and persistent liver decompensation occurred in 35% and 10% of patients, respectively.•Textbook outcome was achieved in 34% of patients.•The laparoscopic approach was identified as a predictor of postoperative liver decompensation and textbook outcome.
There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. ...One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies.
CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls.
The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients.
Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLe(x)) along ...with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLe(x) and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLe(x) and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•The method enables relative quantitation of hAGP glycans from pathological samples•Pancreatic cancer samples clearly showed an increase of hAGP fucosylated glycans.•Fucosylated ...glycans could be potential biomarkers for diagnosing pancreatic cancer.•The established method could be extremely useful to find novel glycoprotein biomarkers
In this work we demonstrate the potential of glycan reductive isotope labeling (GRIL) using 12C- and 13C-coded aniline and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry (μZIC-HILIC-ESI-MS) for relative quantitation of glycosylation variants in selected glycoproteins present in samples from cancer patients. Human α1-acid-glycoprotein (hAGP) is an acute phase serum glycoprotein whose glycosylation has been described to be altered in cancer and chronic inflammation. However, it is not clear yet whether some particular glycans in hAGP can be used as biomarker for differentiating between these two pathologies. In this work, hAGP was isolated by immunoaffinity chromatography (IAC) from serum samples of healthy individuals and from those suffering chronic pancreatitis and different stages of pancreatic cancer, respectively. After de-N-glycosylation, relative quantitation of the hAGP glycans was carried out using stable isotope labeling and μZIC-HILIC-ESI-MS analysis. First, protein denaturing conditions prior to PNGase F digestion were optimized to achieve quantitative digestion yields, and the reproducibility of the established methodology was evaluated with standard hAGP. Then, the proposed method was applied to the analysis of the clinical samples (control vs. pathological). Pancreatic cancer samples clearly showed an increase in the abundance of fucosylated glycans as the stage of the disease increases and this was unlike to samples from chronic pancreatitis. The results gained here indicate the mentioned glycan in hAGP as a candidate structure worth to be corroborated by an extended study including more clinical cases; especially those with chronic pancreatitis and initial stages of pancreatic cancer. Importantly, the results demonstrate that the presented methodology combining an enrichment of a target protein by IAC with isotope coded relative quantitation of N-glycans can be successfully used for targeted glycomics studies. The methodology is assumed being suitable as well for other such studies aimed at finding novel cancer associated glycoprotein biomarkers.
Abstract Background The International Study Group for Liver Surgery (ISGLS) proposed a definition for bile leak after liver surgery. A multicentre international prospective study was designed to ...evaluate this definition. Methods Data collected prospectively from 949 consecutive patients on specific datasheets from 11 international centres were collated centrally. Results Bile leak occurred in 69 (7.3%) of patients, with 31 (3.3%), 32 (3.4%) and 6 (0.6%) classified as grade A, B and C, respectively. The grading system of severity correlated with the Dindo complication classification system ( P < 0.001). Hospital length of stay was increased when bile leak occurred, from a median of 7 to 15 days ( P < 0.001), as was intensive care stay ( P < 0.001), and both correlated with increased severity grading of bile leak ( P < 0.001). 96% of bile leaks occurred in patients with intra-operative drains. Drain placement did not prevent subsequent intervention in the bile leak group with a 5–15 times greater risk of intervention required in this group ( P < 0.001). Conclusion The ISGLS definition of bile leak after liver surgery appears robust and intra-operative drain usage did not prevent the need for subsequent drain placement.
Despite recent advances in the medical treatment of metastatic colorectal cancer (mCRC), which include irinotecan- and oxaliplatin-based first-line regimens, the concept of planned sequential therapy ...involving three active agents during the course of a patient's treatment and the increasing use of targeted monoclonal antibodies, 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with CRC liver metastases, liver resection remains the only chance of cure, with 5-year survival rates ranging from 25% to 40%. However, 80% to 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. The rapid expansion in the use of improved combination chemotherapy regimens plus or minus biologics, to render initially unresectable metastases resectable has increased the percentage of patients eligible for potentially curative surgery. However, the current staging criteria for CRC patients with metastatic disease do not reflect these recent changes or the fact that there is also a large variation in the survival of patients with stage IV CRC. For example the survival for a patient with a solitary, resectable liver metastasis is better than that for a patient with stage III disease. A new staging system is therefore needed that acknowledges both the improvements that have been made in surgical techniques for resectable metastases and the impact of modern chemotherapy on rendering initially unresectable CRC liver metastases resectable, while at the same time distinguishing between patients with a chance of cure at presentation and those for whom only palliative treatment is possible.
Through-silicon vias (TSVs) technology has attracted industry interest as a way to achieve high bandwidth, and short interconnect delays in nanometer three-dimensional integrated circuits (3-D ICs). ...However, TSVs are critical elements susceptible to undergoing defects at steps, such as fabrication and bonding or during their lifetime. Resistive open defects have become one of the most frequent failure mechanisms affecting TSVs. They include microvoids, underfilling, misalignment, pinholes in the oxide, or misalignment during bonding, among others. Although considerable research effort has been made to improve the coverage of TSV testing, little attention has been paid to weak (resistive) open defects causing small delays. In this work, a postbond oscillation test strategy to detect such small delay defects is proposed. Variations in the duty cycle of transmitted signals after unbalanced logic gates are shown to help in the detection of weak open defects in TSVs. HSPICE simulations, including process parameter variations, have been considered, and results show the effectiveness of the method in the detection of weak open defects above 1 kΩ. Experimental work on a 65-nm IC also corroborates the detection capability of the proposal.
Prebond Testing of Weak Defects in TSVs Arumi, Daniel; Rodriguez-Montanes, Rosa; Figueras, Joan
IEEE transactions on very large scale integration (VLSI) systems,
04/2016, Letnik:
24, Številka:
4
Journal Article, Publication
Recenzirano
Odprti dostop
Through-silicon vias (TSVs) are critical elements in 3-D integrated circuits susceptible to defects during fabrication and lifetime. It is desirable to detect defective TSVs in the early steps of the ...fabrication process to prevent stacking yield loss. Thus, the development of effective prebond testing techniques becomes of great importance. In this direction, recent research effort has been devoted to the development of two main prebond techniques: 1) prebond probing and 2) built-in self-test (BIST) techniques. The prebond probing poses economic and technological challenges, whereas current BIST proposals have disadvantages for certain solutions. Hence, there is still a need for an effective methodology in terms of fault coverage, area overhead, and test time. This paper proposes a BIST technique based on a simple unbalanced circuit comparing the behavior of two TSVs. Electrical simulation results show the viability of the proposal to detect weak defects, i.e., resistive opens and resistive bridges, adding reasonable area overhead in a short-test application time. Furthermore, an experimental design is built on a 65-nm technology, where resistive open defects are intentionally injected. Automated test equipment measurements confirm the simulation results.
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