Prophylactic total gastrectomy for familial gastric cancer.

BACKGROUND: An autosomal dominant syndrome of diffuse gastric cancer has been reported with germline mutations in the E-cadherin (CDH1) gene and has been identified in approximately 14 families and 50 individuals worldwide. Penetrance of the gene is 70% to 80%, and the average age of onset of gastric cancer is 37 years. These characteristics have led to the consideration of prophylactic total gastrectomy in family members with CDH1 mutations. METHODS: We report here the first use of prophylactic gastrectomy in 6 asymptomatic members of 2 families (2 males, 4 females; ages 22, 27, 28, 35, 39, and 40) based on family pedigree and genetic analysis. Total gastrectomy was performed via an upper midline incision, and reconstruction of the gastrointestinal tract was done via a Roux-en-Y esophagojejunostomy. Complete removal of all gastric mucosa was documented intraoperatively, and confirmation was made that only esophageal mucosa remained at the proximal specimen margin. RESULTS: The gastric specimens appeared normal, and the results of routine pathologic examination were negative for cancer. All specimens from patients who tested positive for E-cadherin mutations were subjected to a research protocol of microscopic sectioning in which 150 to 250 tissue blocks were examined. All of these patients had microscopic foci of cancer, often at multiple sites, with overlying normal gastric mucosa. CONCLUSIONS: E-cadherin gene mutations in association with familial gastric cancer is a new disease for which prophylactic surgery must be considered. The morbidity of this operation is much higher than that for other genetic diseases, but the alternative is a mortality risk of more than 80% at a young age.

Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations.

BACKGROUND: Germ-line truncating mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer. These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance, predominantly in young persons. We describe genetic screening, surgical management, and pathological findings in young persons with truncating mutations in CDH1 from two unrelated families with hereditary diffuse gastric cancer. METHODS: Mutation-specific predictive genetic testing was performed by polymerase-chain-reaction amplification, followed by restriction-enzyme digestion and DNA sequencing in Family 1 and by heteroduplex analysis in Family 2. A total gastrectomy was performed prophylactically in five carriers of mutations who were between 22 and 40 years old. In each case, the entire mucosa of the stomach was extensively sampled for microscopical analysis. RESULTS: Superficial infiltrates of malignant signet-ring cells were identified in the surgical samples from all five persons who underwent gastrectomy. These early diffuse gastric cancers were multifocal in three of the five cases, and in one person infiltrates of malignant signet-ring cells were present in 65 of the 140 tissue blocks analyzed, representing in aggregate less than 2 percent of the gastric mucosa. CONCLUSIONS: We recommend genetic counseling and consideration of prophylactic gastrectomy in young, asymptomatic carriers of germ-line truncating CDH1 mutations who belong to families with highly penetrant hereditary diffuse gastric cancer.

An objective analysis of process errors in trauma resuscitations.

OBJECTIVE: A computer-based system to apply trauma resuscitation protocols to patients with penetrating thoracoabdominal trauma was previously validated for 97 consecutive patients at a Level 1 trauma center by a panel of the trauma attendings and further refined by a panel of national trauma experts. The purpose of this article is to describe how this system is now used to objectively critique the actual care given to those patients for process errors in reasoning, independent of outcome. METHODS: A chronological narrative of the care of each patient was presented to the computer program. The actual care was compared with the validated computer protocols at each decision point and differences were classified by a predetermined scoring system from 0 to 100, based on the potential impact on outcome, as critical/noncritical/no errors of commission, omission, or procedure selection. RESULTS: Errors in reasoning occurred in 100% of the 97 cases studied, averaging 11.9/case. Errors of omission were more prevalent than errors of commission (2. 4 errors/case vs 1.2) and were of greater severity (19.4/error vs 5. 1). The largest number of errors involved the failure to record, and perhaps observe, beside information relevant to the reasoning process, an average of 7.4 missing items/patient. Only 2 of the 10 adverse outcomes were judged to be potentially related to errors of reasoning. CONCLUSIONS: Process errors in reasoning were ubiquitous, occurring in every case, although they were infrequently judged to be potentially related to an adverse outcome. Errors of omission were assessed to be more severe. The most common error was failure to consider, or document, available relevant information in the selection of appropriate care.

Familial gastric cancer: overview and guidelines for management.

Families with autosomal dominant inherited predisposition to gastric cancer have been described. More recently, germline E-cadherin/CDH1 mutations have been identified in hereditary diffuse gastric cancer kindred. The need to have protocols to manage and counsel these families in the clinic led a group of geneticists, gastroenterologists, surgeons, oncologists, pathologists, and molecular biologists to convene a workshop to produce consensus statements and guidelines for familial gastric cancer. Review of the available cancer pathology from people belonging to families with documented germline E-cadherin/CDH1 mutations confirmed that the gastric cancers were all of the diffuse type. Criteria to define the different types of familial gastric cancer syndromes were agreed. Foremost among these criteria was that review of histopathology should be part of the evaluation of any family with aggregation of gastric cancer cases. Guidelines for genetic testing and counselling in hereditary diffuse gastric cancer were produced. Finally, a proposed strategy for clinical management in families with high penetrance autosomal dominant predisposition to gastric cancer was defined.

Prediction of outcome in intensive care unit trauma patients: a multicenter study of Acute Physiology and Chronic Health Evaluation (APACHE), Trauma and Injury Severity Score (TRISS), and a 24-hour intensive care unit (ICU) point system.

OBJECTIVE: To conduct a multicenter study to validate the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II system, APACHE III system, Trauma and Injury Severity Score (TRISS) methodology, and a 24-hour intensive care unit (ICU) point system for prediction of mortality in ICU trauma patient admissions. METHODS: The study population consisted of retrospectively identified, consecutive ICU trauma admissions (n = 2,414) from six Level I trauma centers. Probabilities of death were calculated by using logistic regression analysis. The predictive power of each system was evaluated by using decision matrix analysis to compare observed and predicted outcomes with a decision criterion of 0.50 for risk of hospital death. The Youden Index (YI) was used to compare the proportion of patients correctly classified by each system. Measures of model calibration were based on goodness-of-fit testing (Hosmer-Lemeshow statistic less than 15.5) and model discrimination were based on the area under the receiver operating characteristic curve (AUC). RESULTS: Overall, APACHE II (sensitivity, 38%; specificity, 99%; YI, 37%; H-L statistic, 92.6; AUC, 0.87) and TRISS (sensitivity, 52%; specificity, 94%; YI, 46%; H-L statistic, 228.1; AUC, 0.82) were poor predictors of aggregate mortality, because they did not meet the acceptable thresholds for both model calibration and discrimination. APACHE III (sensitivity, 60%; specificity, 98%; YI, 58%; H-L statistic, 7.0; AUC, 0.89) was comparable to the 24-hour ICU point system (sensitivity, 51%; specificity, 98%; YI, 50%; H-L statistic, 14.7; AUC, 0.89) with both systems showing strong agreement between the observed and predicted outcomes based on acceptable thresholds for both model calibration and discrimination. The APACHE III system significantly improved upon APACHE II for estimating risk of death in ICU trauma patients (p < 0.001). Compared with the overall performance, for the subset of patients with nonoperative head trauma, the percentage correctly classified was decreased to 46% for APACHE II; increased to 71% for APACHE III (p < 0.001 vs. APACHE II); increased to 59% for TRISS; and increased to 62% for 24-hour ICU points. For operative head trauma, the percentage correctly classified was increased to 60% for APACHE II; increased to 61% for APACHE III; decreased to 43% for TRISS (p < 0.004 vs. APACHE III); and increased to 54% for 24-hour ICU points. For patients without head injuries, all of the systems were unreliable and considerably underestimated the risk of death. The percentage of nonoperative and operative patients without head trauma who were correctly classified was decreased, respectively, to 26% and 30% for APACHE II; 33% and 29% for APACHE III; 33% and 19% for TRISS; 20% and 23% for 24-hour ICU points. CONCLUSION: For the overall estimation of aggregate ICU mortality, the APACHE III system was the most reliable; however, performance was most accurate for subsets of patients with head trauma. The 24-hour ICU point system also demonstrated acceptable overall performance with improved performance for patients with head trauma. Overall, APACHE II and TRISS did not meet acceptable thresholds of performance. When estimating ICU mortality for subsets of patients without head trauma, none of these systems had an acceptable level of performance. Further multicenter studies aimed at developing better outcome prediction models for patients without head injuries are warranted, which would allow trauma care providers to set uniform standards for judging institutional performance.

Comparison of mammographically guided breast biopsy techniques.

OBJECTIVE: To determine which mammographically guided breast biopsy technique is the most efficient in making a diagnosis in women with suspicious mammograms. SUMMARY BACKGROUND DATA: Mammographically guided biopsy techniques include stereotactic 14-gauge core-needle biopsy (SC bx), stereotactic 11-gauge suction-assisted core biopsy (Mammotome [Mbx]), stereotactic coring excisional biopsy (Advanced Breast Biopsy Instrument [ABBI]), and wire-localized biopsy (WL bx). Controversy exists over which technique is best. METHODS: All patients undergoing any one of these biopsy methods over a 15-month period were reviewed, totaling 245 SC bx, 107 Mbx, 104 ABBI, and 520 WL bx. Information obtained included technical success, pathology, discordant pathology, and need for open biopsy. RESULTS: Technical success was achieved in 94.3% of SC bx, 96.4% of Mbx, 92.5% of ABBI, and 98.7% of WL bx. The sensitivity and specificity were 87.5% and 98.6% for SC bx, 87.5% and 100% for Mbx, and 100% and 100% for ABBI. Discordant results or need for a repeat biopsy occurred in 25.7% of SC bx, 23.2% of Mbx, and 7.5% of ABBI biopsies. In 63.6% of ABBI and 50.9% of WL bx, positive margins required reexcision; of the cases with positive margins, 71.4% of ABBI and 70.4% of WL bx had residual tumor in the definitive treatment specimen. CONCLUSION: Although sensitivities and specificities of SC bx and Mbx are good, 20% to 25% of patients will require an open biopsy because a definitive diagnosis could not be reached. This does not occur with the ABBI excisional biopsy specimen. The positive margin rates and residual tumor rates are comparable between the ABBI and WL bx. The ABBI avoids operating room and reexcision costs; therefore, in appropriately selected patients, this appears to be the most efficient method of biopsy.

Racial differences in the presentation and surgical management of breast cancer.

BACKGROUND: African American women are seen with more advanced breast cancers, are less likely to be treated with breast-conserving surgery, and generally have poorer prognoses than white women. There are a myriad of potential causes for these phenomena. The purpose of this study was to measure racial differences in the surgical treatment of breast cancer among women with comparable health care access and delivery. METHODS: The Breast Cancer Registry of the Department of Surgery at Henry Ford Hospital was accessed for all patients between January 1, 1990, and December 31, 1997 for whom data on race, tumor characteristics, stage, and treatment specifics were available. Socioeconomic information was collected with use of 1990 census block data. Proportions of women who received each treatment were compared for African Americans and whites with use of the relative risk (RR) and 95% confidence intervals (CI). We used multiple logistic regression to obtain estimates of the relative risk, controlling for potential confounding factors. RESULTS: Of the 1699 patients in the database, 1250 had sufficient information for analysis. A total of 8.7% of African American women were diagnosed with late-stage disease (i.e., stage III or IV) compared with 7.9% of whites. Nevertheless, African American women had a lower frequency of stage I disease (30.5% vs 36.2%) and a higher frequency of stage II disease (36.8% vs 31.4%). Overall and adjusted risk estimates for age, tumor stage, marital status, median income, and type of insurance revealed no substantive or statistically significant differences between African American and white patients. The adjusted RR for local excision was 1.39 (95% CI 0.78 to 2.49), for lumpectomy and axillary dissection RR 0.92 (95% CI 0.66 to 1.29), for simple mastectomy RR 0.84 (95% CI 0.41 to 1.72), and for modified radical mastectomy RR 1.00 (95% CI 0.73 to 1.36). CONCLUSIONS: In this setting of equal access to health care, African American women still have higher frequencies of stage II disease, although the frequencies for late-stage disease are similar. Nevertheless, no surgical differences were found in this population, even after the effects of socioeconomic indicators and stage at diagnosis were controlled for Survival differences between African American and white women are unlikely to be explained by differences in treatment.

Are universal precautions realistic?

In concluding whether universal precautions are necessary, it certainly appears that we need something to reduce the significant problem of HIV transmission to health-care providers. As occupational risk goes, it exceeds the occupational risk of a number of other high-risk professions. Unfortunately, we do not know if universal precautions are effective. We also do not know the true compliance rate in use of universal precautions, nor whether they have an impact on transmission even if effectively used. What are the alternatives? They are not great, but some have not been adequately explored or implemented. Re-engineering around needle use in the hospital is clearly the most likely area to produce concrete results, because needlesticks are overwhelmingly the greatest source of infection, but this has not been encouraged to the degree it could be, even with systems already developed. Universal testing does not appear to be a viable alternative, for numerous reasons already discussed. Finally, are universal precautions more important for other pathogens than HIV? I would say yes. Hepatitis B, hepatitis C, and nosocomial infections are more important both as public health issues and as health-care provider prevention issues. If universal precautions are effective in reducing any of these, they are worthwhile.

Epidemiology of injuries by needles and other sharp instruments. Minimizing sharp injuries in gynecologic and obstetric operations.

Surgical and obstetric HCWs and epidemiologists will benefit from working together to describe the frequency and circumstances of percutaneous injuries in operating and delivery rooms. Rates of percutaneous injury vary among institutions, and attending and resident surgeons are among those at greatest risk for injury. Gynecologic surgery appears to have one of the highest rates of injury of the surgical specialties, and rates of injury vary by procedure within a given specialty. Suture needles cause the majority of injuries. Certain actions such as holding tissue while suturing or cutting are associated with a higher risk of injury. Many percutaneous injuries appear to be preventable. Epidemiologic data can be used to develop strategies based on the industrial hygiene model to reduce the incidence of percutaneous injury and to collect and disseminate data on the efficacy of new preventive measures. Potentially safer instruments and suture needles, technique modification strategies, and personal protective equipment such as cut-resistant gloves and finger protective strips are now available. Scientific assessment is needed of these and other new measures to determine whether they will decrease the risk of percutaneous injury, be acceptable to users, be cost effective, and avoid adverse consequences to patients or HCWs.

Cytogenetic analysis of thyroid tumors after cryopreservation.

Current cytogenetic evaluation of solid tumors is performed on fresh tissue specimens requiring on-call tissue culture facilities. The application of cryopreservation to tumor samples prior to cytogenetic analysis allows collection of tumors to a desired sample size. We evaluated methods of cryopreservation for their effects on growth potential from 11 benign thyroids and one papillary thyroid cancer. Mitotic indices and thyroglobulin expression applying imunocytology were analyzed. Compared to fresh tumors, the revived tumor samples showed unaltered thyroglobulin expression. A statistically significant (p < 0.004) prolongation to develop mitotic activity occurred in samples received after the freezing of dispase digested tissues, but not in samples frozen as thinly cut pieces. In addition, the data show that cytogenetic analysis at the 400-band level can be achieved in cryopreserved thyroid tissues.

Effect of interferon gamma on infection-related death in patients with severe injuries. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of interferon gamma in reducing infection and death in patients sustaining severe injury. DESIGN: Multicenter, randomized, double-blind, placebo-controlled trial with observation for 60 days and until discharge for patients with major infection on day 60. SETTING: Nine university-affiliated level 1 trauma centers. PATIENTS: Four hundred sixteen patients with severe injuries, assessed by Injury Severity Score and degree of contamination. INTERVENTION: Recombinant human interferon gamma, 100 micrograms, was administered subcutaneously once daily for 21 days (or until patient discharge if prior to 21 days) as an adjunct to standard antibiotic and supportive therapy. MAIN OUTCOME MEASURES: Incidence of major infection, death related to infection, and death. RESULTS: Infection rates were similar in both treatment groups; however, patients treated with interferon gamma experienced fewer deaths related to infection (seven [3%] vs 18 [9%]; P = .008) and fewer overall deaths (21 [10%] vs 30 [14%]; P = .17). While 12 early deaths (days 1 through 7) occurred in each treatment group, late death occurred in 18 placebo-treated patients and nine in interferon gamma-treated patients. The results were dominated by findings at one center, which had the highest enrollment and higher infection and death rates. Statistical analysis did not eliminate the possibility of an unidentified imbalance between arms as an explanation for the results. CONCLUSION: Further evaluation is required to determine the validity of the observed reduction in infection-related deaths in patients treated with interferon gamma.

Prevention of venous thromboembolism in trauma patients.

Trauma patients are at risk for thromboembolic complications, but effective methods of prophylaxis have not been established for this heterogenous population. In this prospective trial, 400 trauma patients were assigned to one of three groups, depending upon their injuries, and randomized within each group to a treatment mode: Group I: sequential gradient pneumatic leg compression (SCD), low-dose subcutaneous heparin (H), or control (C); Group II: H or C; Group III: SCD or C. Venous duplex ultrasound examinations were performed on admission and weekly thereafter. Of the 251 patients who completed the study, 15 (6%) developed lower extremity venous thrombosis and two additional patients developed pulmonary embolism (one fatal). Significant risk factors associated with the development of thromboembolism included immobilization > 3 days, age 30 years or older, and the presence of pelvic or lower extremity fractures. In patients with neurotrauma who cannot receive heparin (Group III), the SCD was more effective than control in preventing DVT (p = 0.057). Neither H nor SCD appeared to offer protection for the other groups of trauma patients, but surveillance with ultrasound examinations allowed for prompt recognition and treatment of occult deep vein thrombosis.

The effects of adrenergic agents on oxygen delivery and oxygen consumption in normal dogs.

This study measured changes in whole body Do2 and Vo2 caused by the administration of exogenous adrenergic agents given at physiologically relevant doses. Using 25-kg nonseptic dogs, we calculated Do2 and directly measured Vo2 in six groups (saline control, colloid fluid challenge, dopamine, dobutamine, norepinephrine, and epinephrine). The dogs were anesthetized with isoflurane, paralyzed, and maintained at a minimum baseline temperature of 37 degrees C. Measurements were taken at six time points: baseline, after each of four successively larger doses of drug, and after a recovery period. Our results demonstrated no significant changes in Vo2 in either the saline control or colloid challenge groups over the 6-hour experiment despite marked increases in cardiac output and oxygen delivery during colloid challenge. At the maximum dose used, adrenergic agents increased Vo2 by the following: dopamine, 56%; dobutamine, 51%; norepinephrine, 43%; epinephrine, 61%. We conclude that adrenergic agents cause a significant increase in whole body Vo2 at moderate doses in normal dogs.

Changes in oxygen consumption relative to oxygen delivery in endotoxemic dogs given adrenergic agents.

Adrenergic agents (AAs) have been used in critically ill patients to increase oxygen delivery (DO2). Associated parallel increases in oxygen consumption (VO2) have been noted and are thought to represent improved tissue oxygen utilization at supraphysiologic levels of DO2. We hypothesize that the increase in VO2 associated with the use of AAs in septic animals is secondary to direct, obligate, metabolic effects of the agents themselves. In this study, mongrel dogs were anesthetised, paralyzed, and had minimum temperature maintained on a warming blanket. Pulmonary and systemic hemodynamics were monitored. DO2 was calculated, while VO2 was measured directly with a metabolic cart. All dogs were given an Escherichia coli challenge and a colloid fluid resuscitation. Two hours after the onset of endotoxemia, baseline values were obtained, followed by four progressively larger doses of saline, dobutamine, or dopamine. At each dose there was a 40-min stabilization period and a 20-min measurement of hemodynamics and VO2. Data were analyzed using analysis of variance with a Scheffe's S test. P values of < 0.05 were considered significant. The control group slowly decreased VO2 during the 6-hr experiment to 73% of baseline. Dobutamine increased VO2 to 119% of baseline (31% above control) and dopamine to 111% of baseline (28% over control). We conclude that adrenergic agents cause a significant increase in whole body VO2 at moderate doses in septic dogs. It is likely, therefore, that the "pathologic" relationship between VO2 and DO2 described in critically ill patients is partially due to the direct metabolic effects of AAs.

The role of duplex ultrasound arterial imaging in patients with penetrating extremity trauma.

OBJECTIVE: To investigate the role of color-flow duplex ultrasound vascular imaging in screening patients for potential arterial injuries following penetrating trauma of the extremities. DESIGN: In this prospective study, patients with penetrating trauma in proximity to major peripheral vessels but without signs of arterial injury underwent color-flow duplex imaging. Patients with abnormal color-flow duplex examination results were then studied with angiography, and the results of the two studies were compared. In patients who presented with signs of arterial injury, immediate operative exploration and/or angiography was performed. SETTING: An urban trauma center. PATIENTS: Patients entering the trauma center with penetrating trauma between April 1991 and December 1992. RESULTS: Seventy-seven patients with 86 extremity injuries were initially screened with color-flow duplex imaging. Four patients had positive study results, and all injuries were confirmed with angiography (100% true positive). No missed arterial injuries were detected in clinical follow-up. CONCLUSIONS: Color-flow duplex imaging reliably detects occult arterial injuries and may also have a role in following up minor injuries treated without surgery.

Can adult trauma surgeons care for injured children?

Large urban trauma centers care for injured children as well as adults in many areas of the country, but the quality of care in these hospitals has not been evaluated versus that available at pediatric trauma centers. The recent validation of TRISS methodology in pediatric populations allowed us to evaluate the quality of pediatric trauma care being provided in a level I trauma center treating injured patients of all ages. We reviewed the records of 353 injured children (aged 0-17 years) who were admitted to our trauma center over a 30-month period for the following data: demographics, mechanism of injury, initial physiologic status (RTS), surgical procedures required, need for intensive care, nature and severity of the injuries (ISS), and outcome. TRISS analysis allowed us to compare our population with the Major Trauma Outcome Study. Only two of the 21 total deaths (overall mortality, 6%) were unexpected, and there were seven unexpected survivors. One hundred twenty-one patients underwent emergency surgical procedures and 63 required admission to the intensive care unit. The Z scores ranged from +0.32 for the children aged less than 2 years to +3.98 for the older age group (14-17 years). We conclude that the quality of care for pediatric trauma patients admitted to trauma centers that care for patients of all ages compares favorably with national standards. In most areas of the country, improvements in pediatric trauma care will likely come from addressing the special needs of injured children in general trauma centers rather than from developing separate pediatric facilities.

The Surgical Infection Society's policy on human immunodeficiency virus and hepatitis B and C infection. The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis.

The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis of The Surgical Infection Society has outlined its policy regarding three deadly blood-borne viral infections. The risk of transmission of these microbes, the role of preoperative testing, the problem of the human immunodeficiency virus-infected surgeon, and conduct in the operating room are discussed.