A proposed algorithm for evaluation and management of pediatric hemophilia patients who present to the emergency department with head trauma.

Hemophilia is the deficiency of plasma clotting factor VIII (hemophilia A) or IX (hemophilia B) where management focuses on the prevention and treatment of acute bleeding symptoms and their sequelae. The most concerning risk is for life-threatening bleeding, including intracranial hemorrhage (ICH), which is caused by head trauma. Guidelines exist for the evaluation and management of pediatric head trauma, including the Pediatric Emergency Care Applied Research Network (PECARN) protocol, but limited evidence exists for when hemophilia patients present to the emergency department (ED), specifically with head trauma. Literature is limited regarding ICH and hemophilia, which further supports the culture of uncertainty among providers. The objective of this study is to conduct a retrospective chart review to determine the prevalence and clinical characteristics of ICH, and to describe computed tomography (CT) scan use in hemophilia patients who present to Phoenix Children's Hospital (PCH) ED with head trauma from January 1, 2007 to June 1, 2019. A total of 89 ED visits and 43 patients met inclusion criteria, and prevalence of ICH was determined to be 4% with the patients presenting with varied clinical characteristics and few commonalities. Using these data, we propose a new algorithm to aid clinicians in determining the need for CT scan in pediatric hemophilia patients who present to the ED with head trauma.

Transcriptional regulation of immediate-early gene response by THOC5, a member of mRNA export complex, contributes to the M-CSF-induced macrophage differentiation.

Hematopoiesis and commitment to a restricted lineage are guided by a timely expressed set of cytokine receptors and their downstream transcription factors. A member of the mRNA export complex, THOC5 (suppressors of the transcriptional defects of hpr1 delta by overexpression complex 5) is a substrate for several tyrosine kinases such as macrophage colony-stimulating factor (M-CSF) receptor and various leukemogenic tyrosine kinases, such as Bcr-Abl, or NPM-ALK. THOC5 tyrosine phosphorylation is elevated in stem cells from patients with chronic myeloid leukemia, suggesting that THOC5 may be involved in leukemia development. THOC5 is also an essential element in the maintenance of hematopoiesis in adult mice. In this report, we show that THOC5 is located in the nuclear speckles, and that it is translocated from the nucleus to cytoplasm during M-CSF-induced bone marrow-derived macrophage differentiation. Furthermore, we have identified THOC5 target genes by trancriptome analysis, using tamoxifen-inducible THOC5 knockout macrophages. Although only 99 genes were downregulated in THOC5-depleted macrophages, half of the genes are involved in differentiation and/or migration. These include well-known regulators of myeloid differentiation inhibitor of DNA binding (Id)1, Id3, Smad family member 6 (Smad6) and Homeobox (Hox)A1. In addition, a subset of M-CSF-inducible genes, such as Ets family mRNAs are THOC5 target mRNAs. Upon depletion of THOC5, unspliced v-ets erythroblastosis virus E26 oncogene homolog (Ets1) mRNA was accumulated in the nucleus. Furthermore, THOC5 was recruited to chromatin where Ets1 was transcribed and bound to unspliced and spliced Ets1 transcripts, indicating that THOC5 has a role in processing/export of M-CSF-inducible genes. In conclusion, regulation of immediate-early gene response by THOC5, a member of mRNA export complex contributes to the M-CSF-induced macrophage differentiation.

Regulation of NF-κB activity by competition between RelA acetylation and ubiquitination.

The nuclear factor (NF)-κB transcription factor has essential roles in inflammation and oncogenesis. Its ubiquitous RelA subunit is regulated by several post-translational modifications, including phosphorylation, ubiquitination and acetylation. Ubiquitination promotes the termination of RelA-dependent transcription, but its regulation is incompletely understood. Through mass spectrometry analysis of ubiquitinated RelA, we identified seven lysines that were attached to degradative and non-degradative forms of polyubiquitin. Interestingly, lysines targeted for acetylation were among the residues identified as ubiquitin acceptor sites. Mutation of these particular sites resulted in decreased polyubiquitination. Acetylation and ubiquitination were found to inhibit each other, consistent with their use of overlapping sites. Reconstitution of rela(-/-) fibroblasts with wild-type and mutant forms of RelA revealed that modifications at these residues can have activating and inhibitory functions depending on the target gene context. Altogether, this study elucidates that ubiquitination and acetylation can modulate each other and regulate nuclear NF-κB function in a gene-specific manner.

Macrophages from patients with atopic dermatitis show a reduced CXCL10 expression in response to staphylococcal α-toxin.

BACKGROUND: Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus (S. aureus), one-third of them producing α-toxin, which is correlated with the severity of eczema in AD. Staphylococcus aureus colonizes in patients with psoriasis as well. Distinct expression of chemokine (C-C motif) ligand (CCL) and chemokine (C-X-C motif) ligand (CXCL) chemokines has been documented in both diseases. In this study, we investigated the effects of sublytic α-toxin concentrations on human macrophages that accumulate in the skin of patients with AD and psoriasis. METHODS: IFN-γ-induced protein of 10-kDa (IP-10)/CXCL10 and macrophage-derived chemokine (MDC)/CCL22 production were evaluated at the mRNA or at the protein level using qRT-PCR or ELISA, respectively. Cell surface markers' expression and chemotaxis were determined by flow cytometry and Boyden chamber technique, respectively. RESULTS: Sublytic concentrations of α-toxin strongly induced CXCL10 in macrophages at both the mRNA and the protein levels and significantly up-regulated MHC class II expression. Supernatants of α-toxin-stimulated macrophages induced the migration of human CD4+ lymphocytes via the CXCL10 receptor (CXCR3). Macrophages from patients with AD produced lower levels of CXCL10 compared to cells from patients with psoriasis as well as healthy controls in response to α-toxin. α-Toxin did not lead to a large variation in CCL22 production in macrophages from all three groups. CONCLUSIONS: Staphylococcal α-toxin contributes to Th1 polarization by induction of CXCL10 in macrophages. Macrophages from patients with AD and psoriasis responded to α-toxin in the induction of Th1-related chemokine CXCL10 diversely, which could favour the recruitment of distinct leucocyte subsets into the skin.

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation.

Constitutively active PI3K catalytic subunit alpha (PIK3CA) interfered with apoptosis induction downstream of death receptor-signaling complex formation allowing robust caspase-8 activation without triggering the execution steps of apoptosis. In mutant PIK3CA-expressing cells, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and CD95L stimulated nuclear factor kappaB (NFkappaB) activation, invasion, and transition to an amoeboid-like morphology. NFkappaB activation and adoption of amoeboid shape were inhibited by caspase-8 knockdown or FLIP-S expression, but only the cell morphology alterations required caspase-8 activity. Furthermore, we identified caspase-8-mediated, caspase-3-independent cleavage of the protein kinase rho-associated, coiled-coil containing protein kinase 1 as a novel mechanism for acquiring amoeboid shape and enhanced invasiveness in response to TRAIL and CD95L. Taken together, we provide evidence that mutated PIK3CA converts the 'tumor surveillance' activity of cancer cell-expressed death receptors and caspase-8 toward tumor promotion.

The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK.

MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired inflammatory response although MK3, which displays extensive structural similarities and identical functional properties in vitro, is still present. Here, we analyze tumor necrosis factor (TNF) production and expression of p38 MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there are no significant differences with wild-type animals. We show that in vivo MK2 and MK3 are expressed and activated in parallel. However, the level of activity of MK2 is always significantly higher than that of MK3. Accordingly, we hypothesized that MK3 could have significant effects only in an MK2-free background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice are viable and show no obvious defects due to loss of compensation between MK2 and MK3. However, there is a further reduction of TNF production and expression of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels.

Molecular mechanisms of T lymphocyte activation: convergence of T cell antigen receptor and IL-1 receptor-induced signaling at the level of IL-2 gene transcription.

Co-stimulation of murine EL-4 thymoma cells-carrying high numbers of TCR and type I IL-1 receptors (IL-1R)-with anti-CD3 antibodies and IL-1 resulted in synergistic enhancement of IL-2 synthesis. While the extracellular signal-regulated kinase (ERK) cascade was activated by both receptors, IL-1 preferentially stimulated Jun-N-terminal kinases (JNK) and p38 mitogen-activated kinase or microtubule-associated protein kinase (MAPK). Interruption of TCR- or IL-1R-stimulated ERK cascade by PD-98059, a specific inhibitor of MAP/ERK kinase (MEK), resulted in partial suppression of nuclear factor of activated T cells activation and in complete inhibition of IL-1-stimulated NFkappaB activation. Suppression of activation of both MEK and p38 MAPK resulted in significant inhibition of IL-2 gene expression. The results show that maximal activation of the IL-2 gene requires activation of at least two different protein kinase cascades, i.e. of the ERK and p38 pathways but presumably also that of JNK which converge at the level of the IL-2 promoter resulting in enhancement of its transcriptional activity.

Induction of interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine- or stress-activated signal transduction pathways.

A hallmark of inflammation is the burst-like formation of certain proteins, initiated by cellular stress and proinflammatory cytokines like interleukin 1 (IL-1) and tumor necrosis factor, stimuli which simultaneously activate different mitogen-activated protein (MAP) kinases and NF-kappaB. Cooperation of these signaling pathways to induce formation of IL-8, a prototype chemokine which causes leukocyte migration and activation, was investigated by expressing active and inactive forms of protein kinases. Constitutively active MAP kinase kinase 7 (MKK7), an activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathway, induced IL-8 synthesis and transcription from a minimal IL-8 promoter. Furthermore, MKK7 synergized in both effects with NF-kappaB-inducing kinase (NIK). Activation of the IL-8 promoter by either of the kinases required functional NF-kappaB and AP-1 sites. While NIK and MKK7 did not affect degradation of IL-8 mRNA, an active form of MKK6, which selectively activates p38 MAP kinase, induced marked stabilization of the transcript and further increased IL-8 protein formation induced by NIK plus MKK7. Consistently, the MAP kinase kinase kinase MEKK1, which can activate NF-kappaB, SAPK/JNK, and p38 MAP kinases, most potently induced IL-8 formation. These results provide evidence that maximal IL-8 gene expression requires the coordinate action of at least three different signal transduction pathways which cooperate to induce mRNA synthesis and suppress mRNA degradation.

The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism.

Stabilization of mRNAs contributes to the strong and rapid induction of genes in the inflammatory response. The signaling mechanisms involved were investigated using a tetracycline-controlled expression system to determine the half-lives of interleukin (IL)-6 and IL-8 mRNAs. Transcript stability was low in untreated HeLa cells, but increased in cells expressing a constitutively active form of the MAP kinase kinase kinase MEKK1. Destabilization and signal-induced stabilization was transferred to the stable beta-globin mRNA by a 161-nucleotide fragment of IL-8 mRNA which contains an AU-rich region, as well as by defined AU-rich elements (AREs) of the c-fos and GM-CSF mRNAs. Of the different MEKK1-activated signaling pathways, no significant effects on mRNA degradation were observed for the SAPK/JNK, extracellular regulated kinase and NF-kappaB pathways. Selective activation of the p38 MAP kinase (=SAPK2) pathway by MAP kinase kinase 6 induced mRNA stabilization. A dominant-negative mutant of p38 MAP kinase interfered with MEKK1 and also IL-1-induced stabilization. Furthermore, an active form of the p38 MAP kinase-activated protein kinase (MAPKAP K2 or MK2) induced mRNA stabilization, whereas a negative interfering MK2 mutant interfered with MAP kinase kinase 6-induced stabilization. These findings indicate that the p38 MAP kinase pathway contributes to cytokine/stress-induced gene expression by stabilizing mRNAs through an MK2-dependent, ARE-targeted mechanism.

Stress-activated protein kinase/Jun N-terminal kinase is required for interleukin (IL)-1-induced IL-6 and IL-8 gene expression in the human epidermal carcinoma cell line KB.

The cytokine interleukin-1 (IL-1) is a major inflammatory hormone which activates a broad range of genes during inflammation. The signaling mechanisms triggered by IL-1 include activation of several distinct protein kinase systems. The stress-activated protein kinase (SAPK), also termed Jun N-terminal kinase (JNK), is activated particularly strongly by the cytokine. In an attempt to delineate its role in activation of gene expression by IL-1, we inhibited the IL-1-induced SAPK/JNK activity by stable overexpression of either a catalytically inactive mutant of SAPKbeta (SAPKbeta(K-R)) or antisense RNA to SAPKbeta in human epidermal carcinoma cells. A detailed analysis of signal transduction in those cells showed that activation of neither NFkappaB nor p38 mitogen-activated protein kinase was affected, suggesting that we achieved specific blockade of the SAPK/JNK. In untransfected and vector-transfected KB cells, IL-1 induced a strong increase in expression of IL-6 and IL-8 mRNA, along with the synthesis of high amounts of the proteins. In two KB cell clones stably overexpressing the mutant SAPKbeta(K-R), and three clones stably overexpressing antisense RNA to SAPKbeta, expression of IL-6 and IL-8 in response to IL-1 was strongly reduced at both the mRNA and protein level. These data indicate that the SAPK/JNK pathway provides an indispensable signal for IL-1-induced expression of IL-6 and IL-8.

The interleukin-1 receptor accessory protein (IL-1RAcP) is essential for IL-1-induced activation of interleukin-1 receptor-associated kinase (IRAK) and stress-activated protein kinases (SAP kinases).

Interleukin-1 (IL-1) is a central mediator of the immune system involved in acute and chronic inflammatory responses. Although the sequences of two types of IL-1 receptors are known, the exact molecular events resulting in signal transduction and coupling to downstream signaling elements remain unclear. The recently cloned IL-1 receptor accessory protein (IL-1RAcP) has been suggested as a co-receptor molecule for IL-1RI, supported by the observation that its expression correlates to IL-1 responsiveness. We transfected the EL-4 subline D6/76 with IL-1RAcP cDNA. This cell line is an IL-1 non-responder expressing IL-1RI but lacking constitutive IL-1RAcP expression. The expression of IL-1RAcP in EL-4 D6/76 was sufficient to restore IL-1-induced activation of interleukin-1 receptor-associated kinase and of stress-activated protein kinases, translocation of the transcription factors NFkappaB and IL-1 NF to the nucleus, and induction of IL-2 mRNA synthesis. These results proved that IL-1RAcP is an indispensible molecule in the IL-1 receptor signal transduction complex, necessary to link events on the plasma membrane level to downstream signaling pathways, allowing IL-1-dependent activation of transcription factors and gene expression.

Surgery for biliary obstruction by tumour thrombus in primary liver cancer.

Five patients with primary liver cancer presented with obstructive jaundice due to extension of tumour thrombus into the biliary ducts. Three patients had hepatocellular carcinoma, two of whom had alcoholic cirrhosis, and the other two had a peripheral cholangiocarcinoma. Preoperative diagnosis of biliary thrombus was best achieved by ultrasonography and computed tomography which showed peripheral hepatic tumour with dilated bile ducts containing dense material. All patients underwent liver resection associated with biliary exploration, clearance and T-tube drainage. Major hepatectomy was required in four cases. There were no postoperative deaths; one patient developed a subphrenic collection of bile which was drained percutaneously. All patients survived more than a year; median survival was 29 months. There are two long-term survivors without recurrence at 29 and 80 months. Patients with primary liver cancer and jaundice due to migrated tumour fragments in the common bile duct may benefit from surgical resection which can result in long-term resolution of symptoms and occasional cure.

Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1.

Inhibitors of protein synthesis, such as anisomycin and cycloheximide, lead to superinduction of immediate-early genes. We demonstrate that these two drugs activate intracellular signaling pathways involving both the mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) cascades. The activation of either pathway correlates with phosphorylation of the c-fos regulatory transcription factor Elk-1. In HeLa cells, anisomycin stabilizes c-fos mRNA when protein synthesis is inhibited to only 50%. Under these conditions, anisomycin, in contrast to cycloheximide, rapidly induces kinase activation and efficient Elk-1 phosphorylation. However, full inhibition of translation by either drug leads to prolonged activation of SAPK activity, while MAPK induction is transient. This correlates with prolonged Elk-1 phosphorylation and c-fos transcription. Elk-1 induction and c-fos activation are also observed in KB cells, in which anisomycin strongly induces SAPKs but not MAPKs. Purified p54 SAPK alpha efficiently phosphorylates the Elk-1 C-terminal domain in vitro and comigrates with anisomycin-activated kinases in in-gel kinase assays. Thus, Elk-1 provides a potential convergence point for the MAPK and SAPK signaling pathways. The activation of signal cascades and control of transcription factor function therefore represent prominent processes in immediate-early gene superinduction.

Interleukin 1 alpha activates two forms of p54 alpha mitogen-activated protein kinase in rabbit liver.

We have identified in rabbits two hepatic forms of T669 peptide kinases that are very strongly activated after systemic injection with the inflammatory cytokine interleukin 1 (IL-1). The T669 peptide contains a major phosphorylation site of the epidermal growth factor receptor, threonine 699 and is a substrate for mitogen-activated protein (MAP) kinases. The kinases were purified to homogeneity and corresponded to 50- and 55-kD proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino acid sequencing of 12 tryptic peptides of both kinases identified them as p54 MAP kinase alpha. This kinase belongs to the novel family of stress-activated protein kinases. This is the first evidence of IL-1 activating a specific protein kinase in vivo.

Interleukin-1 activates a novel protein kinase that phosphorylates the epidermal-growth-factor receptor peptide T669.

We have isolated from KB cells stimulated with interleukin-1 (IL-1) a protein kinase that phosphorylates a peptide (T669) based on the sequence around T669 of the epidermal growth factor (EGF) receptor. The enzyme, which had an apparent molecular mass of 45 kDa on gel-filtration chromatography, was purified 170,000-fold from cytosolic extracts by sequential chromatography on Mono Q, Mono S, phenyl-Sepharose, Superose 12, ATP-Sepharose and Mono Q. The enzyme activity co-chromatographed at the last step with a 45 kDa protein band that stained for phosphotyrosine. This peak fraction also contained some actin and a 60 kDa protein that stained weakly for phosphotyrosine. The T669 peptide is a substrate for mitogen-activated protein (MAP) kinase. Amounts of IL-1-induced T669 kinase and activated recombinant p42 MAP kinase having equal activity on T669 peptide were compared on commonly used MAP kinase substrates. T669 kinase was two or three orders of magnitude less active on myelin basic protein or microtubule-associated protein-2 than was MAP kinase. The IL-1-induced T669 kinase did not react with antiserum to p42/p44 MAP kinase. It was inactivated by treatment with protein phosphatase 2A or protein phosphotyrosine phosphatase 1B, so it may be regulated by dual phosphorylation in similar fashion to MAP kinase. The dephosphorylated enzyme was not re-activated by MAP kinase kinase. This novel enzyme could lie on a kinase cascade induced by IL-1. It may be responsible for phosphorylating T669 of the EGF receptor.

Interleukin 1 and tumour necrosis factor activate the mitogen-activated protein (MAP) kinase kinase in cultured cells.

Interleukin 1 (IL1) activated mitogen-activated protein (MAP) kinase kinase in human gingival and foreskin fibroblasts and KB cells. Maximal activity was found in cytosolic extracts made after stimulating cells for 15 min. On anion-exchange chromatography two differently charged forms of MAP kinase kinase were identified, both phosphorylated a kinase-defective mutant MAP kinase, and activated recombinant wild type MAP kinase to phosphorylate MBP. Both were inhibited by an antiserum to recombinant MAP kinase kinase and the less acidic form was identified on Western blotting as an antigen of approximately 43 kDa. Indistinguishable forms were very much more strongly induced by phorbol myristate acetate (PMA). TNF had a similar effect to that of IL1.

Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand-sewn? A prospective, multicenter, randomized trial.

440 patients were prospectively enrolled in a randomized, multicenter trial to compare 4 types of manual (84 interrupted end-to-end, 77 continuous end-to-end, 82 interrupted end-to-side, and 91 continuous end-to-side) (polyglycolic derived suture) and 1 type of stapled (106 side-to-side with GIA+TA devices) ileocolonic anastomosis after right hemicolectomy for carcinoma. The trial was designed according to Schwartz' pragmatic formulation. All 5 groups were well-matched, except for a lower rate of intraoperative sepsis in the stapled group (P < 0.02). The main end point was anastomotic leakage detected clinically or by routine sodium diatrizoate enema on the 8-10th postoperative day. Results showed that stapled ileocolonic anastomosis was associated with less anastomotic leakages (2.8%) than all the other techniques combined (8.3%). In spite of the fact that staples are approximately ten times more expensive, our results suggest performing side-to-side (GIA+TA) mechanical anastomosis after right resection for carcinoma.

[Resection of hepatocellular carcinomas. Analysis of prognostic factors of a multicenter series of 153 patients]. / Résection des carcinomes hépatocellulaires. Analyse des facteurs pronostiques d'une série multicentrique de 153 malades.

In order to identify the prognostic factors of the resection of hepatocellular carcinoma, the results of 153 resections performed between January 1984 and December 1988 in 18 French centers were analysed. Cirrhosis was present in 76% of the patients. Among the postoperative complications (61%), the most frequent were ascites (35.3%) and liver failure (19%). Operative mortality was 20%. One-, 3- and 5-year survival rates were 52.7, 30.1, and 17.9%, respectively. The survival rate was significantly higher in patients with a curative resection, Pugh's class A or with a tumor less than 3 centimeters in diameter. After curative resection, actuarial survival rates without recurrence were 65, 24.4, and 16.7% after, 1, 3, and 4 years respectively. In this case, the survival rate was significantly related to the number of resected nodules and the size of the tumor but not to the presence of a capsule surrounding the tumor.

[Nodular regenerative hyperplasia of the liver associated with azathioprine therapy]. / Hyperplasie nodulaire régénérative du foie associée à la prise d'azathioprine.

Three cases of nodular regenerative hyperplasia of the liver associated with azathioprine therapy are reported. The indication of azathioprine differed in each of the 3 cases including kidney transplantation, graft-versus-host disease following bone marrow transplantation, and suspicion of bowel inflammatory disease, respectively. In all three patients, nodular regenerative hyperplasia was discovered after a prolonged administration of azathioprine (24 to 40 months), with a cumulative dose of 52 to 120 g. Under light microscopy, vascular lesions were associated with nodular regenerative hyperplasia in the 3 cases and consisted of sinusoidal dilatation (2 cases), perisinusoidal fibrosis (2 cases), and peliosis (1 case). In two patients, nodular regenerative hyperplasia was responsible for severe portal hypertension which was treated by portacaval shunt. These findings are strongly suggestive of a role of azathioprine in the occurrence of nodular regenerative hyperplasia. The mechanism of azathioprine-induced nodular regenerative hyperplasia could be related to sinusoidal lesions caused by azathioprine and responsible for liver hypoperfusion, with regenerative hyperplasia in the areas remaining normally perfused. Patients receiving long-term therapy with azathioprine should be followed-up regularly and liver biopsy should be performed when clinical or biochemical liver abnormalities are observed.

[The best anastomoses after colonic resection]. / Le point sur les meilleures anastomoses après résection colique.

Among the numerous anastomotic techniques after colonic resection, the mechanical sutures using staplers have been credited with a lower incidence of anastomotic leakage than hand-sewn anastomoses. This hypothesis has been tested in two multicentre, prospective, randomized trials after right hemicolectomy for carcinoma and after left colectomy with colorectal anastomosis. After right hemicolectomy, the stapled anastomosis using the GIA and TA staplers appeared to be superior to all hand-sewn anastomoses. This superiority was not apparent after left colectomy followed by colorectal anastomosis. Although the leakage rate of stapled anastomoses was similar to hand-sewn anastomoses, they carry a high rate of intra-operative mishaps. Furthermore, the stapler does not permit a lower anastomosis in this study. Finally, the overall cost of a stapled anastomosis is superior to the cost of an hand-sewn anastomosis.