Analysis of the impact of EEA stapler size on risk of anastomotic complications in colorectal anastomosis: does size matter?

BACKGROUND: Colorectal anastomotic complications are dreaded and dramatically affect outcomes. Causes are multifactorial, with the size of the end-to-end anastomosis (EEA) stapler a modifiable factor and potential target for risk reduction. Our goal was to examine the impact of the EEA stapler size on the risk of anastomotic complications in left-sided colorectal resections. METHODS: A prospective divisional database was reviewed for consecutive elective left-sided resections with a colorectal anastomosis using an EEA stapler from January 2013 May 2018 inclusive. Patients were stratified into 25-29 mm or 30-33 mm cohorts. Patient and disease demographics, operative variables, and postoperative outcomes were evaluated. The main outcome measures were the rate and factors associated with anastomotic complications. RESULTS: Four hundred seventy-three cases were evaluated, 185 ( 39.1%) were in the 25-29 mm group and 288 (60.9%) in the 30-33 mm group. Patients were comparable in demographics and operative variables. More males were anastomosed with the 30-33 mm than with the 25-29 mm stapler (57.6% vs 28.6%, p < 0.01). Significantly more patients developed an anastomotic stricture with the 25-29 mm than with the 30-33 mm staplers (7.1% vs. 2.1%; p = 0.007). There was no significant difference in leak rates or reoperation/interventions between groups. On logistic regression, neither gender, operative indication nor approach were associated with anastomotic leak, readmission, or reoperation/intervention. Stapler size remained significantly associated with stricture (p = 0.032). CONCLUSIONS: The 25-29 mm EEA staplers were associated with an increased rate of anastomotic stricture compared to 30-33 mm staplers in left-sided colorectal anastomoses. As stapler size is a simple process measure that is easily modifyable, this is a potential target for improving anastomotic complication rates. Further controlled trials may help assess the impact of stapler size on improving patient and quality outcomes.

The modulation of lymphocyte functions by molecules secreted by macrophages. II. Conditions leading to increased secretion.

Cultures of peritoneal exudate cells rich in macrophages were studied for the secretion of lymphostimulatory molecules. Two conditions produced increased secretion: (a) addition to the cultures of various agents that readily interacted with macrophages, such as latex particles, antibody-coated red cells, endotoxin, Listeria organisms, or Be salt; or (b) addition of activated lymphocytes. In the first case the increased activity was found during the first 24 or 48 h after uptake of the stimuli. Increased activity was found in normal or peptone-stimulated macrophages but not in macrophages after injection of endotoxin or thioglycollate. The addition of T lymphocytes from Listeria-infected mice to macrophage cultures increased greatly the activities. This increase was also produced by addition to antigen-primed T cells together with antigen. The lymphocytes by themselves did not secrete active factors. The lymphostimulatory activities were tested on thymocyte DNA synthesis and on antibody formation in vitro. The latter assay was done on spleen cells from immunized mice where one striking effect was the stimulation of differentiation to antibody-secreting cells. Some dissociation of both activities (thymocyte DNA synthesis and B-cell differentiation) was observed with selected culture fluids.

The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis.

Culture fluids of peritoneal exudate cells rich in macrophages stimulated DNA synthesis of thymocytes and, to lesser extent, of spleen cells. We also investigated the effects of culture fluids from macrophages on the in vitro response to a hapten-carrier protein (fluorescein-menocyanin) using spleen cells from immune mice. Macrophage culture fluids contained an activity that increased the plaque-forming cell response of both IgG and IgM class. This increase was observed in the absence of any added hapten protein to the culture. The helper function of T lymphocytes (as evidenced by challenging with the hapten on the homologous carrier) was also increased by the macrophage culture fluid. However, this enhancement was best observed in conditions of relatively low T-cell activity. Also, the macrophage fluid allowed spleen cells of nude athymic mice to make a plaque-forming cell response to sheep red blood cells of both the IgM and IgG class. The macrophage was the cell source of the stimulatory molecule since it was generated only in cultures of macrophages devoid of significant number of lymphocytes. Stimulatory activity was not found in cultures of lymphocytes, mouse embryo cells, or 3T3 cells. The thymocyte stimulatory molecule did not contain H-2 antigens, was resistant to diisopropylfluorophosphate treatment, eluted from Sephadex with a size ranging from 15,000 to 21,000 daltons, and was sensitive to chymotrypsin and pepsin.

Inhibition of E-selectin gene expression by transforming growth factor beta in endothelial cells involves coactivator integration of Smad and nuclear factor kappaB-mediated signals.

Transforming growth factor (TGF)-beta(1) is a pleiotropic cytokine/growth factor that is thought to play a critical role in the modulation of inflammatory events. We demonstrate that exogenous TGF-beta(1) can inhibit the expression of the proinflammatory adhesion molecule, E-selectin, in vascular endothelium exposed to inflammatory stimuli both in vitro and in vivo. This inhibitory effect occurs at the level of transcription of the E-selectin gene and is dependent on the action of Smad proteins, a class of intracellular signaling proteins involved in mediating the cellular effects of TGF-beta(1). Furthermore, we demonstrate that these Smad-mediated effects in endothelial cells result from a novel competitive interaction between Smad proteins activated by TGF-beta(1) and nuclear factor kappaB (NFkappaB) proteins activated by inflammatory stimuli (such as cytokines or bacterial lipopolysaccharide) that is mediated by the transcriptional coactivator cyclic AMP response element-binding protein (CREB)-binding protein (CBP). Augmentation of the limited amount of CBP present in endothelial cells (via overexpression) or selective disruption of Smad-CBP interactions (via a dominant negative strategy) effectively antagonizes the ability of TGF-beta(1) to block proinflammatory E-selectin expression. These data thus demonstrate a novel mechanism of interaction between TGF-beta(1)-regulated Smad proteins and NFkappaB proteins regulated by inflammatory stimuli in vascular endothelial cells. This type of signaling mechanism may play an important role in the immunomodulatory actions of this cytokine/growth factor in the cardiovascular system.

Characterization of resident glomerular cells in the rat expressing Ia determinants and manifesting genetically restricted interactions with lymphocytes.

The existence of a subpopulation of rat glomerular cells bearing Ia determinants has been demonstrated with the aid of techniques for the enzymatic isolation and culture of glomerular cells. The Ia-positive cell is normally resident in the uninflamed glomerulus. It resembles a mononuclear phagocyte and consists of a functionally heterogeneous cell population with the capacity of Fc receptor display and phagocytosis, both in vivo and in vitro. A new technique for labeling these cells in situ in intact glomeruli has indicated that Ia-positive cells make up approximately 2% of the total glomerular cell population. The isolated glomerular cells can take up antigen and stimulate immune lymphocytes in an I-region-restricted interaction. They are strongly stimulatory in an allogeneic primary mixed lymphocyte culture. Characterization of this cell type suggests potential new insights into the pathogenesis of renal allograft rejection and immunologically mediated glomerulonephritis.

Interleukin-8 induces changes in human neutrophil actin conformation and distribution: relationship to inhibition of adhesion to cytokine-activated endothelium.

Interleukin-8 (IL-8) induces diverse biological responses in neutrophils, including inhibition of adhesion to cytokine-activated endothelium, which we have termed the leukocyte adhesion inhibition (LAI) effect. Pretreatment of neutrophils with cytochalasin B abolished the LAI effect of IL-8, suggesting a microfilament-dependent mechanism. Interleukin-8 induced a rapid increase (less than or equal to 15 s) in the polymerization of actin filaments in human neutrophils that was blocked by pretreatment with cytochalasin B. F-actin depolymerization occurred gradually at a rate inversely proportional to IL-8 concentration. This temporal pattern of actin polymerization-depolymerization was similar to that induced by other chemotactic factors such as C5a and N-formylmethionyl-leucyl-phenylalanine, which also exhibit a marked LAI effect, but the lipid mediators, leukotriene B4 and platelet-activating factor, lack any significant LAI effect. Scanning confocal microscopy demonstrated that neutrophil actin microfilaments undergo a dramatic rearrangement prior to detachment of the neutrophil from a surface. We suggest that the ability of IL-8 and certain other leukocyte agonists to regulate the actin polymer network of neutrophils may play an important role in adhesive interactions with the vascular endothelium.

Changes in outcome following surgery for colorectal cancer: one surgeon's experience.

BACKGROUND: Colorectal cancer (CRC) has the second highest mortality rate of all cancers in Ireland. Developments in imaging, surgical technique, and perioperative care in the last two decades have altered management. AIMS: To determine whether outcome following surgery for CRC in the mid-west has changed over a 22-year period. METHODS: Four hundred and twenty-two patients were divided into two time periods: Group A (1980-1991, n = 203) and Group B (1992-2002, n = 219) and demographic, inpatient, and survival data were reviewed. RESULTS: The mean age was 67 years, 59% were male. Group B patients had less advanced disease at presentation (Dukes' stage D 14% vs 22%, p < 0.05), fewer perioperative complications (13% vs 23%, p < 0.05), and fewer local recurrences (6.8% vs 11.8%, p < 0.05) than Group A. No difference in 30-day mortality rate or survival was detected. CONCLUSIONS: Although perioperative CRC management has improved, methods of earlier diagnosis and improvements in adjuvant therapy should be explored to improve survival.

Isolated musculocutaneous neuropathy caused by a proximal humeral exostosis.

We report an isolated musculocutaneous neuropathy caused by a proximal humeral osteochondroma that became symptomatic after the patient played recreational basketball. Lesion resection resulted in complete deficit resolution. Mass lesions involving the musculocutaneous nerve should be considered in patients with atraumatic, isolated musculocutaneous neuropathies that are recurrent or fail to recover, even in the setting of strenuous exercise.

Medical education and health care in Uganda.

Health care and medical education in Uganda, once the best in Black Africa, have been adversely affected by the economic, political, and social upheavals in this developing country during the past decade. Crop failures, inadequate public health measures, shortage of medical equipment and essential drugs, and lack of sufficient medical school faculty have resulted in a major crisis. Substantial aid from the medical profession in developed countries will be necessary to help restore medical practice and education to the level present before the regime of Idi Amin.

Series on pharmacology in practice. 12. Antineoplastic agents.

Drug treatment for cancer is now widely utilized and in selected neoplasms offers the opportunity for prolonged remission or even cure. Knowledge of the clinical pharmacology of these agents is critically important to successful therapy. Severe and potentially fatal toxicity may occur unless these agents are administered with meticulous attention to details by physicians experienced in their use. Knowledge of functional impairment of organs responsible for the metabolic breakdown or excretion of these agents and awareness of drug-drug interactions are essential in guiding selection and dosage. The late complications that may result are particularly relevant in patients who achieve prolonged remission or cure and in those for whom these agents are used for benign disorders.

Short-term international medical service.

There are many opportunities for short-term medical service internationally. Prerequisite preparation must include consideration of motivation, flexibility, culturally sensitive health care, and problems in communication and patient approach. Practical considerations require recognizing the importance of choice of locale, lack of materials and equipment, health concerns, travel, and expenses. A reference for opportunities available and a list of articles suggested as supplementary reading are provided.

Reinduction chemotherapy for acute nonlymphocytic leukemia.

Twenty-four patients who had a relapse after successful treatment of acute nonlymphocytic leukemia were re-treated with a chemotherapeutic program similar to that which produced the initial remission. Eight of the nine patients who achieved a second remission had received a three-drug reinduction regimen consisting of cytosine arabinoside, an anthracycline, and 6-thioguanine. An increased duration of initial remission before relapse (more than 26 weeks) predicted a greater likelihood of achieving a second remission.

Concomitant myelofibrosis with agnogenic myeloid metaplasia and malignant lymphoma.

The concomitant occurrence of non-Hodgkin's lymphoma and agnogenic myeloid metaplasia with myelofibrosis in one patient is described for the first time. Oral therapy with an alkylating agent resulted in partial remission.

Day case laparoscopic cholecystectomy is feasible.

BACKGROUND: Laparoscopic cholecystectomy is the operation of choice for cholelithiasis. AIMS: The aims of our study were to assess the feasibility of day case laparoscopic cholecystectomy (DCLC) in selected patients. METHODS: DCLC was introduced in this unit in July 1999. The first 50 patients were prospectively evaluated up to February 2001. RESULTS: All patients were under 55 years of age with an ASA grade of I (n = 48) or II (n = 2). The mean age was 41.1 years (range 20-55 years) and the male:female ratio was 1:6. All patients had a standard anaesthetic protocol. Patients were discharged 10 to 12 hours postoperatively with a pro forma, which was reviewed at one week in the clinic. The conversion rate was 2%. Three required overnight admission due to excessive nausea, hypertension and for an unforeseen psychosocial problem. Ninety per cent of patients were suitable for same day discharge. No patient required subsequent readmission. CONCLUSION: DCLC is feasible and safe in carefully selected patients and has the advantages of convenience and cost-effectiveness.