The management of postoperative upper alimentary tract fistulas: A single-center experience of endoscopic tissue glue repair and recommendations of a systematic review.

BACKGROUND/PURPOSE: The appropriate management of postoperative upper alimentary tract fistula (UATF) remains uncertain. The efficacy of esophagogastroduodenoscopy (EGD) tissue glue repair in the treatment of patients with postoperative UATF was explored. We also conducted a systematic review of the literature regarding the inpatient management of UATF. METHODS: Totally 24 patients received EGD tissue glue repair for postoperative UATF at our institute from April 2014 to April 2020. Independent characteristics of size of fistula, location of the UATF, complications, and recurrences were analyzed. PubMed and Cochrane Library databases were reviewed. A pooled analysis was performed, and subgroup analysis was conducted separately for different anatomic locations and techniques. RESULTS: With a mean follow-up of 40 months, the fistula failed to close with EGD tissue glue repair in 2 of 24 patients (8.3%). Eight patients required repeated EGD tissue glue repair, which was more frequent in oral or thoracic UATF (p = 0.053), but all achieved a successful seal in the EGD tissue after glue repair alone (n = 22). The fistula size was correlated with the demand for repeated EGD tissue glue repair (p = 0.017). Besides, a total of 30 studies regarding 2356 cases of postoperative UATF between 2010 and 2021 were retrieved and analyzed. Several non-operative methods were generally accepted as the initial approach, with a non-inferior success rate compared to operative techniques. CONCLUSION: The results suggest that no single approach toward UATF is superior in terms of success rate and healing time. The potential advantages of EGD tissue glue repair after drainage were more suitable for patients with postoperative UATF and multiple comorbidities.

Characteristics and outcomes of second cancers in patients with childhood cancer: A report from the Taiwan Pediatric Oncology Group.

BACKGROUND: Patients with childhood cancer are at increased risk for the development of second cancers. METHODS: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. RESULTS: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. CONCLUSION: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

Chemical composition of smoke produced by open versus laparoscopic surgery for cholecystectomy.

BACKGROUND: Smoke produced by traditional open surgery (TOS) has long been considered hazardous to medical staff. Compared with TOS, minimally invasive surgery under carbon dioxide pneumoperitoneum is associated with a faster recovery and less wound pain. However, the impact of oxygen-deficient environment on the chemical contents of smoke has not been comprehensively assessed. METHODS: This research evaluated the chemical composition and volatile organic compound (TVOC) level in smoke produced by open cholecystectomy (OC) versus laparoscopic cholecystectomy (LC) for gallbladder diseases. Smoke samples were collected and analyzed via gas chromatography-mass spectrometry. Chemical compounds were further grouped according to molecular weight and toxicity. RESULTS: Compared with the OC, LC had significantly higher halocarbon and TVOC levels but lower cycloalkene and aldehyde levels. No halocarbons were isolated from OC specimens. When stratified based on molecular weight, LC had a bimodal pattern (i.e., high levels of small-sized [<60 Da] and large-sized [>120 Da] compounds). There was no difference in terms of toxicity types, incidence, and severity associated with detected compounds between two groups. CONCLUSION: LC is associated with a higher TVOC level and proportion of low- and high-molecular-weight organic compounds. Further strategies of evacuating these health hazards and preventing smoke leakage through trocars should be considered.

Glutamine Administration Attenuates Kidney Inflammation in Obese Mice Complicated with Polymicrobial Sepsis.

Obesity is a well-known public health issue around the world. Sepsis is a lethal clinical syndrome that causes multiorgan failure. Obesity may aggravate inflammation in septic patients. Glutamine (GLN) is a nutrient with immune regulatory and anti-inflammatory properties. Since sepsis is a common contributing factor for acute kidney injury (AKI), this study investigated the effects of GLN administration on sepsis-induced inflammation and AKI in obese mice. A high-fat diet which consists of 60% of calories from fat was provided for 10 weeks to induce obesity in the mice. Then, the obese mice were subdivided into sepsis with saline (SS) or GLN (SG) groups. Cecal ligation and puncture (CLP) was performed to produce sepsis. The SS group was intravenously injected with saline while the SG group was administered GLN one or two doses after CLP. Obese mice with sepsis were sacrificed at 12, 24, or 48 h post-CLP. Results revealed that sepsis resulted in upregulated high-mobility group box protein-1 pathway-associated gene expression in obese mice. Also, expressions of macrophage/neutrophil infiltration markers and inflammatory cytokines in kidneys were elevated. Obese mice treated with GLN after sepsis reversed the depletion of plasma GLN, reduced production of lipid peroxides, and downregulated macrophage/neutrophil infiltration and the inflammatory-associated pathway whereas tight junction gene expression increased in the kidneys. These findings suggest that intravenously administered GLN to obese mice after sepsis alleviated inflammation and attenuated AKI. This model may have clinical application to obese patients with a risk for infection in abdominal surgery.

Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries.

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia.

BACKGROUND: This study aimed to investigate the relationship between CD4+ regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy. METHODS: We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100 × 109 /L at 12 months after IVIG treatment. RESULTS: Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho = 0.72) and negatively correlated with both ILC1 (rho = -0.49) and ILC3 (rho = -0.60) (P < 0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n = 8) versus responders (n = 22; P < 0.05). We found that Tregs suppressed proliferation of ILCs and CD4+ T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4+ CD45RO+ T cells in vitro following IVIG therapy. CONCLUSIONS: Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.

Intravenous Arginine Administration Downregulates NLRP3 Inflammasome Activity and Attenuates Acute Kidney Injury in Mice with Polymicrobial Sepsis.

Acute kidney injury (AKI) is a major complication of sepsis. Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein complexes that mediate septic AKI. L-arginine (Arg) is a conditionally essential amino acid in catabolic conditions and a substrate for nitric oxide (NO) production; however, its use in sepsis is controversial. This study investigated the effect of intravenous Arg supplementation on modulating NLRP3 inflammasome activity in relation to septic AKI. Mice were divided into normal control (NC), sham, sepsis saline (SS), and sepsis Arg (SA) groups. In order to investigate the role of NO, L-N6-(1-iminoethyl)-lysine hydrochloride (L-NIL), an inducible NO synthase inhibitor, was administered to the sepsis groups. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg via tail vein 1 h after CLP. Mice were sacrificed at 6, 12, and 24 h after sepsis. The results showed that compared to the NC group, septic mice had higher plasma kidney function parameters and lower Arg levels. Also, renal NLRP3 inflammasome protein expression and tubular injury score increased. After Arg treatment, plasma Arg and NO levels increased, kidney function improved, and expressions of renal NLRP3 inflammasome-related proteins were downregulated. Changes in plasma NO and renal NLRP3 inflammasome-related protein expression were abrogated when L-NIL was given to the Arg sepsis groups. Arg plus L-NIL administration also attenuated kidney injury after CLP. The findings suggest that intravenous Arg supplementation immediately after sepsis restores plasma Arg levels and is beneficial for attenuating septic AKI, partly via NO-mediated NLRP3 inflammasome inhibition.

Effects of the Glutamine Administration on T Helper Cell Regulation and Inflammatory Response in Obese Mice Complicated with Polymicrobial Sepsis.

This study investigated the impacts of GLN on inflammation and T cell dysregulation in obese mice complicated with sepsis. Mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat and was administered for 10 weeks to induce obesity. Mice fed with a high-fat diet were then assigned to sham (SH) and sepsis with saline (SS) or GLN (SG) groups. The SH group was subjected to laparotomy, while the sepsis group underwent cecal ligation and puncture (CLP). The SS group was intravenously injected with saline. The SG group was intravenously administered GLN after CLP. Mice were sacrificed at 12, 24, or 48 h post-CLP, respectively. Results demonstrated that in the presence of obesity, sepsis drove CD4+ T cells toward the helper T (Th)2 and Th17 lineages. Also, expressions of inflammatory cytokines and macrophage infiltration markers in adipose tissues and lungs were elevated. Treatment of obese mice with GLN after sepsis reversed Th polarization and downregulated macrophage infiltration and inflammatory cytokine, whereas the tight junction-associated protein expression increased in the lungs. These findings suggest that the intravenous administration of GLN to obese mice after sepsis modulated a more balanced Th cell lineage, alleviated inflammation, and attenuated lung injury.

Percutaneous embolization for a subacute gastric fistula following laparoscopic sleeve gastrectomy: a case report and literature review.

BACKGROUND: The management for subacute or chronic fistula after bariatric surgery is very complicated and with no standard protocol yet. It is also an Achilles' heel of all bariatric surgery. The aim of this case report is to describe our experience in managing this complication by percutaneous embolization, a less commonly used method. CASE PRESENTATION: A 23-year-old woman with a body mass index of 35.7 kg/m2 presented with delayed gastric leak 7 days after laparoscopic sleeve gastrectomy (LSG) for weight reduction. Persistent leak was still noted under the status of nil per os, nasogastric decompression, and parenteral nutrition for 1 month; therefore, endoscopic glue injection was performed. The fistula tract did not seal off, and the size of pseudocavity enlarged after gas inflation during endoscopic intervention. Subsequently, we successfully managed this subacute gastric fistula via percutaneous fistula tract embolization (PFTE) with removal of the external drain 2 months after LSG. CONCLUSIONS: PFTE can serve as one of the non-invasive methods to treat subacute gastric fistula after LSG. The usage of fluoroscopy-visible glue for embolization can seal the fistula tract precisely and avoid the negative impact from gas inflation during endoscopic intervention.

Effects of prophylactic administration of glutamine on CD4+ T cell polarisation and kidney injury in mice with polymicrobial sepsis.

The present study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarisation and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to three groups: normal control fed with American Institute of Nutrition (AIN)-93G diet and two sepsis groups provided with either AIN-93G-based diet or identical components, except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with caecal ligation and puncture and were killed 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas IL-4-, and forkhead box p3 (Foxp3)-expressing CD4+ T cells percentages were up-regulated. Compared with the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells and reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker kidney injury molecule-1 (Kim-1) were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more balanced blood T helper cell polarisation, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects at risk of abdominal infection.

Are physicians on the same page about do-not-resuscitate? To examine individual physicians' influence on do-not-resuscitate decision-making: a retrospective and observational study.

BACKGROUND: Individual physicians and physician-associated factors may influence patients'/surrogates' autonomous decision-making, thus influencing the practice of do-not-resuscitate (DNR) orders. The objective of this study was to examine the influence of individual attending physicians on signing a DNR order. METHODS: This study was conducted in closed model, surgical intensive care units in a university-affiliated teaching hospital located in Northern Taiwan. The medical records of patients, admitted to the surgical intensive care units for the first time between June 1, 2011 and December 31, 2013 were reviewed and data collected. We used Kaplan-Meier survival curves with log-rank test and multivariate Cox proportional hazards models to compare the time from surgical intensive care unit admission to do-not-resuscitate orders written for patients for each individual physician. The outcome variable was the time from surgical ICU admission to signing a DNR order. RESULTS: We found that each individual attending physician's likelihood of signing do-not-resuscitate orders for their patients was significantly different from each other. Some attending physicians were more likely to write do-not-resuscitate orders for their patients, and other attending physicians were less likely to do so. CONCLUSION: Our study reported that individual attending physicians had influence on patients'/surrogates' do-not-resuscitate decision-making. Future studies may be focused on examining the reasons associated with the difference of each individual physician in the likelihood of signing a do-not-resuscitate order.

Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan.

BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay. Based on presenting features, immunophenotype and genotype, patients were assigned to one of the three risk groups: standard risk (SR), high risk (HR), or very high risk (VHR). The patients with t(1;19)/TCF3-PBX1 were treated in the HR arm receiving more intensive chemotherapy. The outcomes of patients with t(1;19)/TCF3-PBX1 were compared to that of patients with other subtypes of B-precursor ALL (B-ALL). RESULTS: Of the 1,129 patients with B-ALL, 64 (5.7%) had t(1;19)/TCF3-PBX1; 51 of whom were treated in the HR arm, but 11 were treated in the VHR and 2 in the SR arm because of physician's preference. As a group, 64 patients with t(1;19)/TCF3-PBX1 had similar 5-year event-free survival (83.3 ± 4.8%) as those with TEL-AML1 (85.2 ± 3.4%, P = 0.984) or those with hyperdiploidy >50 (84.0 ± 3.1%, P = 0.748). The cumulative risk of any (isolated plus combined) central nervous system relapse among patients with t(1;19)/TCF3-PBX1 (8.7 ± 3.8%) tended to be higher than that of patients with TEL-AML1 (5.8 ± 2.3%, P = 0.749) or those with hyperdiploidy (4.1 ± 1.8%, P = 0.135), albeit the differences did not reach statistical significance. CONCLUSIONS: With contemporary intensive chemotherapy, children with t(1;19)/TCF3-PBX1 fared as well as those with favorable genotypes (TEL-AML1 or hyperdiploidy).

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation.

BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.

Randomized controlled clinical trial assessing the effects of oral nutritional supplements in postoperative gastric cancer patients.

BACKGROUND: Postoperative weight loss and malnutrition are major issues in gastric cancer patients. The concept of oral nutritional supplements (ONS) is gaining widespread acceptance. We investigated the effects of ONS administration on postoperative body weight loss in patients with gastric cancer who had undergone total gastrectomy or distal gastrectomy. METHODS: Patients were randomized to either the treatment or the control group. In both groups, standard surgery for gastric cancer was performed. In the treatment group, intervention with ONS was performed until 12 weeks after discharge. In the control group, patients were fed the usual postoperative diet. Weight, body composition, quality of life, hematological parameters, and blood chemistry were evaluated. RESULTS: We analyzed 113 cases (73 distal gastrectomy, 40 total gastrectomy). Weight loss in the ONS group after total gastrectomy was significantly less than that in the control group. Weight loss and skeletal muscle mass loss after distal gastrectomy did not differ significantly between the ONS and control groups. CONCLUSION: This study showed ONS after total gastrectomy to significantly diminish postoperative weight loss.

Robotic liver donor right hepatectomy: A pure, minimally invasive approach.

Right hepatectomy for a living liver donor via a pure minimally invasive approach is a challenging procedure and only a few cases have been reported. Between May 2013 and August 2015, 13 patients underwent robotic living donor right hepatectomy in our institute, and 54 patients received open surgery. In this series, no conversion was conducted for robotic donor right hepatectomy. The 2 groups shared similar blood loss (169 versus 146 mL), complication rates (7.7% versus 9.3%), and recovery of donor liver function (peak alanine aminotransferase, 269 versus 252 IU/mL). The robotic group needed longer operation time (596 versus 383 minutes) but less postoperative patient-controlled analgesia (0.58 versus 0.84 ng/kg) and a shorter period before returning to work/school (52.9 versus 100.0 days) and sex (100.0 versus 156.0 days). For recipient outcomes regarding the donor procedure, the robotic group shared similar experiences in early allograft dysfunction, complications, and 1-year recipient liver function with the open group. With respect to documented benefits of minimally invasive left-sided liver donor procedure, the development of right donor hepatectomy is slow. In conclusion, with substantial improvements in patient recovery after the minimally invasive approach, the robotic platform would be a big step toward completing pure minimally invasive liver donor surgery. Liver Transplantation 22 1509-1518 2016 AASLD.

Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression.

BACKGROUND: Acetaminophen (APAP) overdose causes acute liver failure (ALF) in animals and humans via the rapid depletion of intracellular glutathione (GSH) and the generation of excess reactive oxygen species (ROS) that damage hepatocytes. Stem cell therapy is a potential treatment strategy for ALF. METHODS: We isolated mesenchymal stem cells (MSCs) from mice omentum adipose tissue-derived stem cells (ASCs) and transplanted them into a mouse model of APAP-induced ALF to explore their therapeutic potential. In addition, we performed in vitro co-culture studies with omentum-derived ASCs and primary isolated hepatocytes to demonstrate the hepatoprotective effect of omentum-derived ASCs on hepatocytes that were subjected to APAP-induced damage. RESULT: ASC transplantation significantly improved the survival rate of mice with ALF and attenuated the severity of APAP-induced liver damage by suppressing cytochrome P450 activity to reduce the accumulation of toxic nitrotyrosine and the upregulation of NF-E2-related factor 2 (Nrf2) expression, resulting in an increase in the subsequent antioxidant activity. These effects protected the hepatocytes from APAP-induced damage through the suppression of downstream MAPK signal activation and inflammatory cytokine production. CONCLUSIONS: our results demonstrate that omentum-derived ASCs are an alternative source of ASCs that regulate the antioxidant response and may represent a beneficial therapeutic strategy for ALF.

Outcomes Following Discontinuation of E. coli l-Asparaginase Upon Severe Allergic Reactions in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Discontinuation of E. coli l-asparaginase in patients with acute lymphoblastic leukemia (ALL) is unavoidable upon severe allergic reaction. We sought to examine outcomes following E. coli l-asparaginase discontinuation due to severe allergic reactions. PROCEDURE: We evaluated the outcome of children enrolled in Taiwan Pediatric Oncology Group-2002-ALL protocol between 2002 and 2012, who had E. coli l-asparaginase discontinued due to severe allergic reactions, and compared the outcomes of those who continued with Erwinia l-asparaginase (Erwinase) with those who did not. RESULTS: Among 700 patients enrolled in this study, 33 patients had E. coli l-asparaginase treatment discontinued due to severe allergic reactions. Five-year overall survival did not differ significantly among the 648 patients without discontinuation (81 ± 1.6%, mean ± SE), compared to 17 patients with allergic reactions and treated with Erwinase (88 ± 7.8%) and 16 patients with allergic reactions but not treated with Erwinase (87 ± 8.6%). Among 16 patients who did not receive Erwinase, all 10 who received ≥50% of the scheduled doses of E. coli l-asparaginase before discontinuation survived without events. CONCLUSIONS: Erwinase treatment may not be needed for some ALL patients with severe allergy to E. coli l-asparaginase if ≥50% of prescribed doses were received and/or therapy is augmented with other agents.

Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment.

UNLABELLED: Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism has not yet been completely defined. Here, we employ a LECT2-affinity column plus liquid chromatography coupled with tandem mass spectrometry to identify LECT2-binding proteins and found that MET receptor strongly interacted with LECT2 protein. Despite the presence of hepatocyte growth factor, the LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET activation also mainly contributes to the blockage of vascular invasion and metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed that the HxGxD motif is primarily responsible for MET receptor binding and its antagonistic effects. CONCLUSION: These findings reveal a novel, specific inhibitory function of LECT2 in HCC by the direct binding and inactivation of MET, opening a potential avenue for treating MET-related liver cancer.

Laparoscopic resection for large gastric gastrointestinal stromal tumor (GIST): intermediate follow-up results.

BACKGROUND: Laparoscopic wedge resection has become a widely accepted treatment for small gastrointestinal stromal tumor (GIST) of the stomach. However, its feasibility as treatment for large gastric GIST is not known. In this retrospective study, the perioperative and oncologic outcomes of laparoscopic wedge resection for gastric GIST (5-8 cm) were reviewed. METHODS: Between November 2002 and December 2012, a total of 39 patients with primary gastric GIST sized 5-8 cm underwent surgery at a tertiary care center, including 18 patients who underwent laparoscopic wedge resection of the stomach (Lap group) and 21 patients who underwent open wedge resection of the stomach (Open group). Clinicopathological parameters were reviewed and compared between the groups. RESULTS: The demographics including age, gender, and body weight were similar between groups. The operative outcomes including blood loss, hospital stay, and surgical complications were also similar, except that operative time was longer in the Lap group (146.6 ± 50.2 vs. 113.3 ± 42.9 min in the Open group, p = 0.03). There was no tumor rupture, conversion of procedures, or major surgical morbidity in either group. The overall median follow-up time was 3.6 years (1.0-11.1). Only one patient in the Lap group had liver metastasis (4 months postoperatively). This patient remains alive 5 years later under imatinib treatment. One patient in the Open group and three patients in the Lap group have died of GIST-unrelated diseases. CONCLUSIONS: Laparoscopic wedge resection of the stomach for primary gastric GIST (5-8 cm) appears to be safe and feasible, with operative and oncological outcomes comparable to those of the open method.

VEGF-D and A Preoperative Serum Levels Predict Nodal and Distant Metastases in Differentiated Thyroid Cancer Patients.

BACKGROUND: Preoperative tumor aggressiveness biomarkers may help surgeons decide the extent of an operation. However, whether serum angiogenetic factors can be used to predict the prognosis of patients with differentiated thyroid cancer is still unclear. METHODS: Seventy-six DTC patients were prospectively recruited. Preoperative serum samples were collected and measured for Tie-2, Ang-1, Ang-2, VEGF-A, and VEGF-D levels. The potential correlations between their serum levels and clinicopathologic features as well as their prognoses were analyzed. RESULTS: Older age (>45 years old) and higher VEGF-A serum levels were independent predictors of extrathyroidal extension. The VEGF-D serum level was an independent factor for lymph node metastases and VEGF-A was an independent factor for distant metastases. None of these serum angiogenetic factors were significantly different between patients who were disease free and those with recurrences. The presence of lymph node metastases was the only independent factor for recurrence over the 2-year follow-up. CONCLUSION: Preoperative serum VEGF-A and VEGF-D levels were significantly elevated in DTC patients with distant and lymph node metastases. These findings, when combined with other clinicopathological factors, may help in surgical decisions.