10535 Hospital Way
Mather CA 95655
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Technical note on ALPPS for a patient with advanced hepatocellular carcinoma associated with invasion of the inferior vena cava. - Hepatobiliary & pancreatic diseases international : HBPD INT
Patients with hepatocellular carcinoma have a very short life expectancy if they receive no surgical intervention. A relatively new surgical technique termed "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) has been employed for inducing rapid hypertrophy of the future liver remnant for patients waiting for hepatectomy. As portal vein embolization may not result in satisfactory hypertrophy before tumor progression occurs, ALPPS can be an alternative for patients with advanced hepatocellular carcinoma. Herein we describe an ALPPS procedure with tumor thrombectomy for a patient who had a small left liver lobe and a large hepatocellular carcinoma involving the whole right liver lobe and the middle hepatic vein and extending into the inferior vena cava. In the first-stage operation, the right portal vein was controlled and divided with a Hemolock. The right hepatic artery was well protected. Hepatic transection was performed with a 1-cm margin from the tumor. The middle hepatic vein trunk was preserved. Ten days afterwards, there was significant hypertrophy of the left lateral section of the liver, and the second-stage operation was conducted. Extended right hepatectomy and tumor thrombectomy were performed under sternotomy and total vascular exclusion. The patient had good recovery and was free of disease 10 months after the operation. ALPPS may be a good treatment option even for patients with advanced disease if carried out at high-volume centers.
Decision-to-delivery intervals and total duration of surgery for caesarean sections in a tertiary general hospital. - Singapore medical journal
This study aimed to determine the decision-to-delivery intervals (DDIs), total duration of surgery and factors influencing these for caesarean sections (CSs).A retrospective study was conducted of all CSs performed from August 2013 to June 2014 at a single tertiary general hospital. Data collected included maternal demographics, indications for CS, category of urgency, DDI, total duration of surgery, grade of first surgeon and number of previous CSs.In total, 488 CSs (Category 1, n = 28; Category 2, n = 137; Category 3, n = 184; Category 4, n = 139) were studied. Overall mean duration of surgery was 41.7 minutes. Mean DDI was 23.9 minutes and 64.5 minutes for Category 1 and Category 2 CSs, respectively. For Category 1 CSs, deliveries during office hours had a significantly shorter DDI than deliveries during out-of-office hours (p < 0.05). For Category 2 CSs, deliveries during office hours had a significantly longer DDI (p < 0.05). Total duration of surgery for senior surgeons was significantly shorter than for trainee surgeons (p < 0.05). Women with no previous CSs had a significantly shorter duration of surgery than those who had one or more (p < 0.05).The majority of women were delivered within the recommended DDI specific to the degree of urgency of CS. The influence of time of day on DDI might be due to challenges of time taken to transfer patients to operating theatres. Total duration of surgery was influenced by surgical experience, history of previous CS and individual surgical styles and preferences.
A review of caesarean section techniques and postoperative thromboprophylaxis at a tertiary hospital. - Singapore medical journal
Although caesarean sections are among the most commonly undertaken procedures in the world, there are wide variations in the surgical techniques used for this procedure. This study aimed to: (a) review the surgical techniques used for caesarean sections by obstetricians working in a tertiary hospital in Singapore; (b) compare the techniques used by these surgeons with those recommended in evidence-based guidelines; and (c) examine the relationship between the technique used and the level of seniority of the surgeons.Data on 490 caesarean sections performed in Singapore General Hospital (SGH) between 1 August 2013 and 30 June 2014 was collected from the Delivery Suite database and reviewed. The surgical techniques studied were closure of the visceral and parietal peritoneum, closure of the uterine layer, use of surgical drains, and use of postoperative thromboprophylaxis.A total of 486 caesarean sections were analysed (4 of the 490 caesarean sections reviewed were excluded due to missing data). Most fetal head deliveries were manual. The majority of surgeons did not close the peritoneum; among those who did, most were senior surgeons. Double-layer uterine closures were done for all cases and drain usage was rare. Among the patients who underwent caesarean sections, 2.0% received grossly inadequate thromboprophylaxis.The surgical techniques currently practiced in SGH are closely aligned with the evidence-based guidelines. Peritoneal closure appears to be associated with the surgeon's early training, with a greater number of senior surgeons being less willing to abandon this step. Closer vigilance in implementing appropriate thromboprophylaxis is recommended.
Endoscopic submucosal dissection vs laparoscopic colorectal resection for early colorectal epithelial neoplasia. - World journal of gastrointestinal endoscopy
To compare the short term outcome of endoscopic submucosal dissection (ESD) with that of laparoscopic colorectal resection (LC) for the treatment of early colorectal epithelial neoplasms that are not amenable to conventional endoscopic removal.This was a retrospective cohort study. The clinical data of all consecutive patients who underwent ESD for endoscopically assessed benign lesions that were larger than 2 cm in diameter from 2009 to 2013 were collected. These patients were compared with a cohort of controls who underwent LC from 2005 to 2013. Lesions that were proven to be malignant by initial endoscopic biopsies were excluded. Mid and lower rectal lesions were not included because total mesorectal excision, which bears a more complicated postoperative course, is not indicated for lesions without histological proof of malignancy. Both ESD and LC were performed by the same surgical unit with a standardized technique. The patients were managed according to a standard protocol, and they were closely monitored for complications after the procedures. All hospital records were reviewed, and the following data were compared between the ESD and LC groups: patient demographics, size and location of the lesions, procedure time, short-term clinical outcomes and pathology results.From 2005 to 2013, 65 patients who underwent ESD and 55 patients who underwent LC were included in this study. The two groups were similar in terms of sex (P = 0.41) and American Society of Anesthesiologist class (P = 0.58), although patients in the ESD group were slightly older (68.6 Â± 9.4 vs 64.6 Â± 9.9, P = 0.03). ESD could be accomplished with a shorter procedure time (113 Â± 66 min vs 153 Â± 43 min, P < 0.01) for lesions of comparable size (3.0 Â± 1.2 cm vs 3.4 Â± 1.4 cm, P = 0.22) and location (colon/rectum: 59/6 vs colon/rectum: 52/3, P = 0.43). ESD appeared to be associated with a lower short-term complication rate, but the difference did not reach statistical significance (10.8% vs 23.6%, P = 0.06). In the LC arm, a total of 22 complications occurred in 13 patients. A total of 7 complications occurred in the ESD arm, including 5 perforations and 2 episodes of bleeding. All perforations were observed during the procedure and were successfully managed by endoscopic clipping without emergency surgical intervention. Patients in the ESD arm had a faster recovery than patients in the LC arm, which included shorter time to resume normal diet (2 d vs 4 d, P = 0.01) and a shorter hospital stay (3 d vs 6 d, P < 0.01).ESD showed better short-term clinical outcomes in this study. Further prospective randomized studies will be required to evaluate the efficacy and superiority of colorectal ESD over LC.
Combined Autoimmune Cytopenias Presenting in Childhood. - Pediatric blood & cancer
Pediatric patients with chronic and/or refractory autoimmune multi-lineage cytopenias present challenges in both diagnosis and management. Increasing availability of diagnostic testing has revealed an underlying immune dysfunction in patients previously diagnosed with Evans Syndrome. However, the data are sparse and the majority of patients are adults.We performed a retrospective chart review to document the natural history of 23 pediatric patients with autoimmune multi-lineage cytopenias followed at three tertiary care pediatric hematology clinics.Investigations revealed seven patients (30.4%) with an autoimmune lymphoproliferative-like syndrome and six patients (26.1%) with other primary immunodeficiencies. Only one (4.3%) patient was suspected to have systemic lupus erythematosus and six patients (26.1%) had other types of autoimmunity. Treatment consisted of immunosuppressive therapy, intravenous gammaglobulin, and splenectomy. Supportive care included granulocyte-colony stimulating factor, and blood product transfusions. Two patients (8.7%) died. Complete remission was achieved in 3 patients (13.0%); of the remaining, 14 patients (60.9%) had chronic immune thrombocytopenic purpura, 10 patients (43.5%) chronic autoimmune neutropenia, and 4 patients (17.4%) chronic autoimmune hemolytic anemia with a median follow up of 5 years (2 months-12 years).These data suggest that pediatric patients presenting with autoimmune multi-lineage cytopenias should undergo investigation for underlying immune dysregulation, including autoimmune lymphoproliferative syndrome, other primary immunodeficiencies and autoimmune disorders. The development of an international registry for such patients is imperative to improve the understanding of their complex natural history.Â© 2015 Wiley Periodicals, Inc.
Antibody-Drug Conjugates (ADCs) Derived from Interchain Cysteine Cross-Linking Demonstrate Improved Homogeneity and Other Pharmacological Properties over Conventional Heterogeneous ADCs. - Molecular pharmaceutics
Conventional antibody-drug conjugates (ADCs) are heterogeneous mixtures of chemically distinct molecules that vary in both drugs/antibody (DAR) and conjugation sites. Suboptimal properties of heterogeneous ADCs have led to new site-specific conjugation methods for improving ADC homogeneity. Most site-specific methods require extensive antibody engineering to identify optimal conjugation sites and introduce unique functional groups for conjugation with appropriately modified linkers. Alternative nonrecombinant methods have emerged in which bifunctional linkers are utilized to cross-link antibody interchain cysteines and afford ADCs containing four drugs/antibody. Although these methods have been shown to improve ADC homogeneity and stability in vitro, their effect on the pharmacological properties of ADCs in vivo is unknown. In order to determine the relative impact of interchain cysteine cross-linking on the therapeutic window and other properties of ADCs in vivo, we synthesized a derivative of the known ADC payload, MC-MMAF, that contains a bifunctional dibromomaleimide (DBM) linker instead of a conventional maleimide (MC) linker. The DBM-MMAF derivative was conjugated to trastuzumab and a novel anti-CD98 antibody to afford ADCs containing predominantly four drugs/antibody. The pharmacological properties of the resulting cross-linked ADCs were compared with analogous heterogeneous ADCs derived from conventional linkers. The results demonstrate that DBM linkers can be applied directly to native antibodies, without antibody engineering, to yield highly homogeneous ADCs via cysteine cross-linking. The resulting ADCs demonstrate improved pharmacokinetics, superior efficacy, and reduced toxicity in vivo compared to analogous conventional heterogeneous ADCs.
Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors. - Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with â‰¤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.Â© 2015 American Association for the Study of Liver Diseases.
A Pan1/End3/Sla1 complex links Arp2/3-mediated actin assembly to sites of clathrin-mediated endocytosis. - Molecular biology of the cell
More than 60 highly conserved proteins appear sequentially at sites of clathrin-mediated endocytosis in yeast and mammals. The yeast Eps15-related proteins Pan1 and End3 and the CIN85-related protein Sla1 are known to interact with each other in vitro, and they all appear after endocytic-site initiation but before endocytic actin assembly, which facilitates membrane invagination/scission. Here we used live-cell imaging in parallel with genetics and biochemistry to explore comprehensively the dynamic interactions and functions of Pan1, End3, and Sla1. Our results indicate that Pan1 and End3 associate in a stable manner and appear at endocytic sites before Sla1. The End3 C-terminus is necessary and sufficient for its cortical localization via interaction with Pan1, whereas the End3 N-terminus plays a crucial role in Sla1 recruitment. We systematically examined the dynamic behaviors of endocytic proteins in cells in which Pan1 and End3 were simultaneously eliminated, using the auxin-inducible degron system. The results lead us to propose that endocytic-site initiation and actin assembly are separable processes linked by a Pan1/End3/Sla1 complex. Finally, our study provides mechanistic insights into how Pan1 and End3 function with Sla1 to coordinate cargo capture with actin assembly.Â© 2015 Sun etÂ al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attributionâ€“Noncommercialâ€“Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Cycling Time Trial Performance 4 Hours After Glycogen-Lowering Exercise Is Similarly Enhanced by Recovery Nondairy Chocolate Beverages Versus Chocolate Milk. - International journal of sport nutrition and exercise metabolism
Postexercise chocolate milk ingestion has been shown to enhance both glycogen resynthesis and subsequent exercise performance. To assess whether nondairy chocolate beverage ingestion post-glycogen-lowering exercise can enhance 20-km cycling time trial performance 4 hr later, eight healthy trained male cyclists (21.8 Â± 2.3y, VO2max = 61.2 Â± 1.4 mlÂ·kg-1Â·min-1; M Â± SD) completed a series of intense cycling intervals designed to lower muscle glycogen (Jentjens & Jeukendrup, 2003) followed by 4 hr of recovery and a subsequent 20-km cycling time trial. During the first 2 hr of recovery, participants ingested chocolate dairy milk (DAIRYCHOC), chocolate soy beverage (SOYCHOC), chocolate hemp beverage (HEMPCHOC), low-fat dairy milk (MILK), or a low-energy artificially sweetened, flavored beverage (PLACEBO) at 30-min intervals in a double-blind, counterbalanced repeated-measures design. All drinks, except the PLACEBO (247 kJ) were isoenergetic (2,107 kJ), and all chocolate-flavored drinks provided 1-g CHOÂ·kg body mass-1Â·h-1. Fluid intake across treatments was equalized (2,262 Â± 148 ml) by ingesting appropriate quantities of water based on drink intake. The CHO:PRO ratio was 4:1, 1.5:1, 4:1, and 6:1 for DAIRYCHOC, MILK, SOYCHOC, and HEMPCHOC, respectively. One-way analysis of variance with repeated measures showed time trial performance (DAIRYCHOC = 34.58 Â± 2.5 min, SOYCHOC = 34.83 Â± 2.2 min, HEMPCHOC = 34.88 Â± 1.1 min, MILK = 34.47 Â± 1.7 min) was enhanced similarly vs PLACEBO (37.85 Â± 2.1) for all treatments (p = .019) These data suggest that postexercise macronutrient and total energy intake are more important for same-day 20-km cycling time trial performance after glycogen-lowering exercise than protein type or protein-to-carbohydrate ratio.
Clinical factors affecting rejection rates in liver transplantation. - Hepatobiliary & pancreatic diseases international : HBPD INT
With improvements in survival, liver transplant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of rejection.We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cellular rejection (ACR) and various clinical factors.Multivariate analysis showed that older age (P=0.04, OR=0.982), chronic hepatitis B virus infection (P=0.005, OR= 0.574), living donor liver transplantation (P=0.02, OR=0.648) and use of interleukin-2 receptor antagonist on induction (P<0.001, OR=0.401) were associated with fewer ACRs. Patients with fulminant liver failure (P=0.004, OR=4.05) were more likely to develop moderate to severe grade ACR.Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver transplantation and use of interleukin-2 receptor antagonist on induction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.
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