Morbidity and mortality of gastrectomy for cancer in Department of Veterans Affairs Medical Centers

BACKGROUND: The purpose of this study was to define risk factors that predict 30-day morbidity and mortality after gastrectomy for cancer in Veterans Affairs (VA) Medical Centers. METHODS: The VA National Surgical Quality Improvement Program prospectively collected data on 708 patients undergoing gastrectomy for cancer in 123 participating VA medical centers from 1991 to 1998. Independent variables included 68 preoperative patient characteristics and 12 intraoperative variables; the dependent variables were 21 defined adverse outcomes and death. Predictive models for 30-day morbidity and mortality were constructed by using stepwise logistic regression analysis. RESULTS: The 30-day morbidity rate was 33.3% (236 of 708). The overall 30-day mortality rate was 7.6% (54 of 708). Significant positive predictors of morbidity (P <.05) included current pneumonia, American Society of Anesthesiologists class IV (threat to life), partially dependent functional status, dyspnea on minimal exertion, preoperative transfusion, extended operative time, and increasing age. Significant positive predictors of mortality (P <.05) included do not resuscitate status, prior stroke, intraoperative transfusion, preoperative weight loss, preoperative transfusion, and elevated preoperative alkaline phosphatase level. CONCLUSIONS: Risk factors predicting morbidity and mortality rates at VA hospitals after gastrectomy for gastric cancer are reported by using a prospectively collected, multi-institutional database. Assigning relative weights to factors associated with adverse outcomes may help improve patient care.     

No difference in clinical outcome after posterolateral lumbar fusion between patients with isthmic spondylolisthesis and those with degenerative disc disease using pedicle screw instrumentation: a comparative study of 112 patients with 4 years of follow-up

We compared the clinical outcome after spinal fusion between patients with isthmic spondylolisthesis and those with degenerative disc disease of the lumbar spine, using multiple logistic regression analysis. A questionnaire describing medication, pain, vocational status and patient satisfaction was mailed to all the patients at a median interval of 4 years after their operation. Fusion was evaluated on plain radiographs at a minimum of 12 months after surgery, and patients were classified as fused or not fused. The overall satisfaction rate was 70%. The results of the present study showed no difference in the outcome after spinal fusion between the two groups of patients. The factors that significantly increased the likelihood of an optimal result - defined as patient satisfaction, return to work, and reduced medication - were male gender, being in work prior to surgery, and being a non-smoker. Since spinal fusion is an expensive treatment with potentially serious risks, and leaves one-third of the patients with an unsatisfactory result, we believe that more studies focusing on the indications for surgery should be performed.     

Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.     

Downsizing Treatment with Tyrosine Kinase Inhibitors in Patients with Advanced Gastrointestinal Stromal Tumors Improved Resectability

Background  

Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT. Most GISTs have mutations in the KIT or PDGFRA gene, causing activation of tyrosine kinase. Imatinib, a tyrosine kinase inhibitor (TKI), is the first-line palliative treatment for advanced GISTs. Sunitinib was introduced for patients with mutations not responsive to imatinib. The aim was to compare the survival of patients with high-risk resected GISTs treated with TKI prior to surgery with historical controls and to determine if organ-preserving surgery was facilitated.     

��-Cell Failure in Diet-Induced Obese Mice Stratified According to Body Weight Gain: Secretory Dysfunction and Altered Islet Lipid Metabolism Without Steatosis or Reduced ��-Cell Mass

OBJECTIVE

C57Bl/6 mice develop obesity and mild hyperglycemia when fed a high-fat diet (HFD). Although diet-induced obesity (DIO) is a widely studied model of type 2 diabetes, little is known about β-cell failure in these mice.

RESEARCH DESIGN AND METHODS

DIO mice were separated in two groups according to body weight gain: low- and high-HFD responders (LDR and HDR). We examined whether mild hyperglycemia in HDR mice is due to reduced β-cell mass or function and studied islet metabolism and signaling.

RESULTS

HDR mice were more obese, hyperinsulinemic, insulin resistant, and hyperglycemic and showed a more altered plasma lipid profile than LDR. LDR mice largely compensated insulin resistance, whereas HDR showed perturbed glucose homeostasis. Neither LDR nor HDR mice showed reduced β-cell mass, altered islet glucose metabolism, and triglyceride deposition. Insulin secretion in response to glucose, KCl, and arginine was impaired in LDR and almost abolished in HDR islets. Palmitate partially restored glucose- and KCl-stimulated secretion. The glucose-induced rise in ATP was reduced in both DIO groups, and the glucose-induced rise in Ca²⁺ was reduced in HDR islets relatively to LDR. Glucose-stimulated lipolysis was decreased in LDR and HDR islets, whereas fat oxidation was increased in HDR islets only. Fatty acid esterification processes were markedly diminished, and free cholesterol accumulated in HDR islets.

CONCLUSIONS

β-Cell failure in HDR mice is not due to reduced β-cell mass and glucose metabolism or steatosis but to a secretory dysfunction that is possibly due to altered ATP/Ca²⁺ and lipid signaling, as well as free cholesterol deposition.While insulin resistance is a common feature in most obese subjects, insulin secretion is increased to compensate for its reduced action and normoglycemia is maintained (1,2). In obese type 2 diabetes subjects, however, β-cell compensation fails due to marked impairment of glucose-stimulated insulin secretion (GSIS), often with reduced β-cell mass (2). The relationship between β-cell function and mass as causative factors in β-cell failure and diabetes progression is debated, with emphasis on the relevance of “functional β-cell mass” rather than total mass (2). Increased adiposity leads to elevated circulating free fatty acids (FFAs) and triglycerides, and in vitro and in vivo studies have indicated a causative role for dyslipidemia in insulin resistance (1,3). Although FFAs are necessary for the amplification of GSIS, their excess supply may also have a role in β-cell failure (4), as prolonged elevation of FFA levels both in vivo and in vitro cause β-cell dysfunction (5,6) and, at least in vitro, apoptosis (7).At least part of the β-cell compensation to insulin resistance is due to an increase in β-cell mass (4). Either long-term high-fat diet (HFD) (8) or a short-term lipid infusion (9) can result in increased β-cell mass without augmentation of GSIS, indicating that β-cell function and mass are not necessarily linked. Rodent studies have indicated that HFD leads to increased β-cell mass (8), which is also observed in normoglycemic obese individuals (10). Unclear at present is the dynamics between the factors driving compensatory increase in β-cell mass and function and those reducing them through the various stages of type 2 diabetes development, particularly as FFA may do both. Genetic islet susceptibility may be a critical determinant of these dynamics, both in humans and animal models (4,11,12).Even though studies employing genetically modified models (e.g., Zucker Diabetic Fatty rats, db/db mice) have helped in understanding some of these pathological processes (13–16), several of these models are of extreme nature, with rapid development of pronounced type 2 diabetes. These models, therefore, differ from human obesity-linked type 2 diabetes, which usually develops more gradually. In an attempt to gain insight into the basis of β-cell failure in a mild model of diabetes, we recently developed a new model of type 2 diabetes, the 60% pancreatectomized obese hyperlipidemic Zucker Fatty rat (14). In this model, severe β-cell dysfunction was found without any evidence of a falling β-cell mass or islet steatosis (14). More detailed examination of the pancreatectomized Zucker Fatty rat islets showed marked depletion of insulin stores and altered glycerolipid metabolism (14). The Zucker Fatty rat, as opposed to the Zucker Diabetic Fatty rat, however, does not have genetic predisposition to diabetes, as it maintains normoglycemia despite severe obesity-related insulin resistance (4). The diet-induced obese (DIO) C57BL/6 mouse gradually develops hyperglycemia (17). This suggests that DIO islets are unable to fully compensate for the obesity-related insulin resistance, as occurs in human type 2 diabetes.In the present study, we investigated β-cell dysfunction in DIO mice stratified into two groups according to the effect of HFD on body weight: the low responders to HFD (LDR) were less obese, developed intermediate severity of insulin resistance, and had only mild impairment in glycemia. The high responders to HFD (HDR) were more obese, insulin resistant, and hyperinsulinemic and were clearly hyperglycemic. Thus, the LDR and HDR groups allowed for analysis and comparison of islet β-cell mass and function in response to different levels of insulin resistance with corresponding very mild perturbation of glucose homeostasis and overt but mild hyperglycemia, respectively. When extended to obese humans, these two groups correspond to the pre-diabetes and early diabetes situations.     

Single Incision Laparoscopic Splenectomy in a 5-Year-Old With Hereditary Spherocytosis

Background:

Single incision laparoscopic surgery (SILS) is an emerging technique that has been used as an approach for appendectomy, cholecystectomy, and splenectomy. We describe the technique of single incision laparoscopic splenectomy for hypersplenism in a 5-year-old boy with spherocytosis.

Case Report:

The patient required blood transfusions for anemia secondary to hypersplenism. His spleen measured 9.8 cm in cranio-caudal length on ultrasound. SILS splenectomy was performed through a 2-cm umbilical incision by using 3 ports. The splenic attachments were taken down using an electrosurgical sealing and cutting device, and the hilum was transected with an endosurgical stapler. The spleen was placed in an endosurgical bag, morcellated, and removed from the abdomen via the umbilical incision without complications. Operative time was 84 minutes; blood loss was minimal.

Conclusion:

SILS splenectomy is feasible in pediatric patients. More experience is needed to assess advantages and disadvantages compared with the standard laparoscopic approach.     

Retrograde flush following topical cooling is superior to preserve the non-heart-beating donor lung

Objective: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD. Methods: Non-heparinized pigs were sacrificed by ventricular fibrillation and divided into three groups (n = 6 per group). After 1 h of in situ warm ischaemia and 2.5 h of topical cooling, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted following an anterograde flush (AF) through the pulmonary artery with 50 ml/kg Perfadex^® (6 °C). Finally, in group III, lungs were retrieved after an identical but retrograde flush (RF) via the left atrium. Flush effluent was sampled at intervals to measure haemoglobin concentration. Performance of the left lung was assessed during 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) of both lungs was calculated as an index of pulmonary oedema. IL-1ß and TNF- protein levels in bronchial lavage fluid from both lungs were compared between groups. Results: Haemoglobin concentration (g/dl) was higher in the first effluent in RF versus AF (3.4 ± 1.1 vs 0.6 ± 0.1; p < 0.05). Pulmonary vascular resistance (dynes × s × cm⁻⁵) was 975 ± 85 RF versus 1567 ± 98 AF and 1576 ± 88 NF at 60 min of reperfusion (p < 0.001). Oxygenation (mmHg) and compliance (ml/cmH₂O) were higher (491 ± 44 vs 472 ± 61 and 430 ± 33 NS, 22 ± 3 vs 19 ± 3 and 14 ± 1 NS, respectively) and plateau airway pressure (cmH₂O) was lower (11 ± 1 vs 13 ± 1 and 13 ± 1 NS) after RF versus AF and NF, respectively. No differences in cytokine levels or in W/D ratios were observed between groups after reperfusion. Histology demonstrated microthrombi more often present after AF and NF compared to RF. Conclusion: Retrograde flush of the lung following topical cooling in the NHBD results in a better washout of residual blood and microthrombi and subsequent reduced pulmonary vascular resistance upon reperfusion.     

Topographical organization of pathways from somatosensory cortex through the pontine nuclei to tactile regions of the rat cerebellar hemispheres

The granule cell layer of the cerebellar hemispheres contains a patchy and noncontinuous map of the body surface, consisting of a complex mosaic of multiple perioral tactile representations. Previous physiological studies have shown that cerebrocerebellar mossy fibre projections, conveyed through the pontine nuclei, are mapped in registration with peripheral tactile projections to the cerebellum. In contrast to the fractured cerebellar map, the primary somatosensory cortex (SI) is somatotopically organized. To understand better the map transformation occurring in cerebrocerebellar pathways, we injected axonal tracers in electrophysiologically defined locations in Sprague-Dawley rat folium crus IIa, and mapped the distribution of retrogradely labelled neurons within the pontine nuclei using three-dimensional (3-D) reconstructions. Tracer injections within the large central upper lip patch in crus IIa-labelled neurons located centrally in the pontine nuclei, primarily contralateral to the injected side. Larger injections (covering multiple crus IIa perioral representations) resulted in labelling extending only slightly beyond this region, with a higher density and more ipsilaterally labelled neurons. Combined axonal tracer injections in upper lip representations in SI and crus IIa, revealed a close spatial correspondence between the cerebropontine terminal fields and the crus IIa projecting neurons. Finally, comparisons with previously published three-dimensional distributions of pontine neurons labelled following tracer injections in face receiving regions in the paramedian lobule (downloaded from http://www.rbwb.org) revealed similar correspondence. The present data support the coherent topographical organization of cerebro-ponto-cerebellar networks previously suggested from physiological studies. We discuss the present findings in the context of transformations from cerebral somatotopic to cerebellar fractured tactile representations.     

Does a Cemented Cage Improve Revision THA for Severe Acetabular Defects?

Background  

Evidence suggests a growing incidence of revision total hip arthroplasty (THA) including a subset with large acetabular defects. Revision THA for severe acetabular bone loss is associated with a relatively high rate of mechanical failure.     

Postoperative falls in the acute hospital setting: characteristics, risk factors, and outcomes in males

Background

Hospital falls are an important cause of morbidity in older surgical patients. The objectives of this study were to describe the characteristics, risk factors, and outcomes for postoperative falls.

Methods

A retrospective study was performed on patients who were admitted to the hospital for more than 23 hours after surgery. Patients who fell within 30 days of their surgery were considered to have experienced a postoperative fall.

Results

Over 5 years and 9,625 inpatient surgical procedures, 154 patients experienced 190 falls. Injuries resulting from postoperative falls included major injury (hip fracture), less than 1%; injury requiring intervention, 2%; injury not requiring intervention, 27%; and no injury, 70%. Variables associated with postoperative falls included older age, functional dependence, lower albumin level, and higher American Society of Anesthesia score.

Conclusions

One or more postoperative falls occurred in 1.6% of surgical inpatients and can lead to significant morbidity. Recognition of fall risk factors will help design postoperative fall prevention programs by identifying patients at highest risk for postoperative falls.