Complex Abdominal Wall Reconstruction with Biologic Mesh for Ventral/Umbilical Hernias in Patients with Cirrhosis: Technique and Outcomes.

INTRODUCTION: Patients with cirrhosis undergoing non-liver transplant surgery have a higher risk or adverse events than those without cirrhosis. The main objectives of this study were to describe characteristics, outcomes, and outcome predictors of cirrhotic patients undergoing complex abdominal wall reconstruction (CAWR) with biologic mesh. MATERIALS AND METHODS: This study had retrospective and prospective components, including all cirrhotic patients at our center with CAWR for ventral/umbilical hernia repair with biologic mesh between December 2016 and November 2021. RESULTS: We studied 37 patients with cirrhosis. Their mean age was 57.2 years, and 64.9% were male. The median body mass index (BMI) was 28.1kg/m2. Ascites was present in 83.3% of patients. The other most common comorbidities were alcohol abuse (67.6%), hypertension (37.8%), and diabetes (24.3%). All complications in aggregate occurred in 11 patients (29.7%). Six patients (16.2%) underwent reoperation. Surgical site infections (SSIs) occurred in five patients (13.5%). Four deaths occurred within 90 days (11.2% cumulative mortality). By 120 days, there were five deaths (14.2% mortality, but none due to the operation). Seven predictor variables achieved an area under the receiver operating characteristic curve (AUROC) for SSI of 0.963, and two predictors yielded an AUROC of 0.825 for 120-day mortality. CONCLUSIONS: Our results suggest that CAWR for ventral/umbilical hernias among cirrhotic patients is feasible given a dedicated CAWR team in collaboration with transplant surgeons and a transplant hepatologist. The rates of adverse outcomes were low or at the midpoint of the range of the study-specific estimates.

Pelvic fractures in severely injured elderly: a double-adjustment propensity score matched analysis from a level I trauma center.

PURPOSE: Pelvic trauma has increased risk of mortality in the elderly. Our study aimed to analyze the impact of the additional burden of pelvic fractures in severely injured elderly. METHODS: This is a retrospective analysis of a prospectively maintained trauma registry from 2012 to 2018 at an American College of Surgeons (ACS) verified Level I Trauma Center. Trauma patients aged ≥ 65 years with ISS ≥ 16 and AIS severity score ≥ 3 in at least two body regions were divided in two groups: group I, consisted of elderly polytrauma patients without pelvic fractures, and group II elderly who had concomitant pelvic fractures. We used a double-adjustment method using propensity score matching (PSM) with subsequent covariate adjustment to minimize the effect of confounding factors, and give unbiased estimation of the impact of pelvic fractures. Balance assessment was conducted by computing absolute standardized mean differences (ASMDs) and ASMD < 0.10 reflects good balance between groups. RESULTS: Of 12,774 patients admitted during this time, 411 (3.2%) elderly with a mean age of 77.75 ± 8.32 years met the inclusion criteria. Of this cohort, only 92 patients (22.4%) had pelvic fractures. Females outnumbered males (55 vs. 45%). Comparing characteristics of group I and group II using ASMDs, pelvic trauma patients were more likely to have higher systolic blood pressure (SBP), head injuries, lower extremity injuries, anticoagulant therapy, and cirrhosis. Fewer variables differed significantly after matching. We observed few instances of worse outcomes associated with pelvic trauma using PSM with and without covariate adjustment. Crude PSM without covariate adjustment, showed a significantly higher rate of deep vein thrombosis (DVT) for pelvic trauma (p < 0.001). Crude PSM also showed a significantly higher rate of ventilator-associated pneumonia (VAP) in group II (p = 0.006). PSM with covariate adjustment did not confirm differences on these outcomes. PSM both without and with covariate adjustment found lower ventilator days and ICU length of stay among patients with pelvic trauma. No significant differences were seen on 12 outcomes: death, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), cardiac arrest with cardiopulmonary resuscitation (CPR), myocardial infarction (MI), pulmonary embolism (PE), unplanned intubation, unplanned admission to intensive care unit (ICU), catheter-associated urinary tract infection (CAUTI), and hospital length of stay. CONCLUSIONS: At a Level I Trauma Center the additional burden of pelvic fractures in seriously injured elderly did not translate into higher mortality. PSM without covariate adjustment suggests worse rates among pelvic trauma patients for DVT and VAP but covariate adjustment removed statistical significance for both outcomes. Pelvic trauma patients had shorter time on ventilator and in the ICU. Whether similar analytic methods applied to patients from larger data sources would produce similar findings remains to be seen.

Early Abdominal Wall Reconstruction with Biologic Mesh is Feasible after Catastrophic Abdominal Wall Disruption from Blunt Trauma.

INTRODUCTION: Traumatic abdominal wall hernias (TAWHs) after blunt trauma, while rare, are typically associated with severe injuries, particularly those involved with the seatbelt triad of abdominal wall disruption. The aim of this study is to present a case series of patients with TAWHs that were managed at an early stage post injury with a biological mesh. MATERIALS AND METHODS: Patients with TAWH undergoing complex abdominal wall reconstruction (CAWR) between 2017 and 2020 were identified from our institutional database. All patients underwent definitive reconstruction using advanced surgical techniques including a posterior component separation with biological mesh (STRATTICE™, Allergan, Inc., Dublin, Ireland) placed in a sublay fashion. RESULTS: Seven patients underwent definitive TAWH repair during their index admission: the median age was 56 years (range 20-77) and the median Injury Severity Score (ISS) was 34 (29-50). The most common mechanism of injury was motor vehicle crash (MVC) at 86%, while the most common intra-abdominal concomitant injury was small bowel. Traumatic hernia location was on the right side of the abdominal wall in three patients, left in three patients, and bilaterally in one patient. There were no hernia recurrences or deaths in this small cohort. CONCLUSION: Traumatic abdominal wall disruption can be safely reconstructed using advanced surgical techniques with a biological mesh during the acute phase or same index hospitalization.

Early versus delayed complex abdominal wall reconstruction with biologic mesh following damage-control surgery.

BACKGROUND: Damage-control surgery for trauma and intra-abdominal catastrophe is associated with a high rate of morbidities and postoperative complications. This study aimed to compare the outcomes of patients undergoing early complex abdominal wall reconstruction (e-CAWR) in acute settings versus those undergoing delayed complex abdominal wall reconstruction (d-CAWR). METHOD: This study was a pooled analysis derived from the retrospective and prospective database between the years 2013 and 2019. The outcomes were compared for differences in demographics, presentation, intraoperative variables, Ventral Hernia Working Grade (VHWG), US Centers for Disease Control and Prevention wound class, American Society of Anesthesiologists (ASA) scores, postoperative complications, hospital length of stay, and readmission rates. We performed Student's t test, χ2 test, and Fisher's exact test to compare variables of interest. Multivariable linear regression model was built to evaluate the association of hospital length of stay and all other variables including the timing of complex abdominal wall reconstruction (CAWR). A p value of <0.05 was considered significant. RESULTS: Of the 236 patients who underwent CAWR with biological mesh, 79 (33.5%) had e-CAWR. There were 45 males (57%) and 34 females (43%) in the e-CAWR group. The ASA scores of IV and V, and VHWG grades III and IV were significantly more frequent in the e-CAWR group compared with the d-CAWR one. Postoperatively, the incidence of surgical site occurrence, Clavien-Dindo complications, comprehensive complication index, unplanned reoperations, and mortality were similar between the two groups. Backward linear regression model showed that the timing of CAWR (ß = -11.29, p < 0.0001), ASA (ß = 3.98, p = 0.006), VHWG classification (ß = 3.62, p = 0.015), drug abuse (ß = 13.47, p = 0.009), and two comorbidities of cirrhosis (ß = 12.34, p = 0.001) and malignancy (ß = 7.91, p = 0.008) were the significant predictors of the hospital length of stay left in the model. CONCLUSION: Early CAWR led to shorter hospital length of stay compared with d-CAWR in multivariable regression model. LEVEL OF EVIDENCE: Therapeutic, level IV.

Biologic Mesh in Surgery: A Comprehensive Review and Meta-Analysis of Selected Outcomes in 51 Studies and 6079 Patients.

BACKGROUND: In recent decades, biologic mesh (BM) has become an important adjunct to surgical practice. Recent evidence-based clinical applications of BM include but are not limited to: reconstruction of abdominal wall defects; breast reconstruction; face, head and neck surgery; periodontal surgery; other hernia repairs (diaphragmatic, hiatal/paraesophageal, inguinal and perineal); hand surgery; and shoulder arthroplasty. Prior systematic reviews of BM in complex abdominal wall hernia repair had several shortcomings that our comprehensive review seeks to address, including exclusion of laparoscopic repair, assessment of risk of bias, use of an acceptable meta-analytic method and review of risk factors identified in multivariable regression analyses. MATERIALS AND METHODS: We sought articles of BM for open ventral hernia repair reporting on early complications, late complications or recurrences and included minimum of 50. We used the quality in prognostic studies risk of bias assessment tool. Random effects meta-analysis was applied. RESULTS: This comprehensive review selected 62 articles from 51 studies that included 6,079 patients. Meta-analytic pooling found that early complications are present in about 50%, surgical site occurrences (SSOs) in 37%, surgical site infections (SSIs) in 18%, reoperation in 7%, readmission in 20% and mortality in 3%. Meta-analytic estimates of late outcomes included overall complications (42%), SSOs (40%) and SSIs (22%). Specific SSOs included seroma (14%), hematoma (4%), abscess (10%), necrosis (5%), dehiscence (8%) and fistula formation (5%). Reoperation occurred in about 17%, mesh explantation in 9% and recurrence in 36%. CONCLUSION: Estimates of nearly all outcomes from individual studies were highly heterogeneous and sensitivity analyses and meta-regressions generally failed to explain this heterogeneity. Recurrence is the only outcome for which there are consistent findings for risk factors. Bridge placement of BM is associated with higher risk of recurrence. Prior hernia repair, history of reintervention and history of mesh removal were also risk factors for increased recurrence.

Clinical Characteristics Predict the Yield of Head Computed Tomography Scans among Intoxicated Trauma Patients: Implications for the Initial Work-up.

BACKGROUND AND AIMS: Alcohol intoxication may confound the clinical assessment of the trauma patient. Head computed tomography (h-CT) is the standard imaging technique to rule out intracranial injury in most intoxicated trauma patients. The objective of this study was to determine whether certain clinical findings (computed clinical score [CCS]) could predict the h-CT yield, admission, and neurosurgical consultation (NSC) among intoxicated trauma patients. MATERIALS AND METHODS: This is a 4-year retrospective cohort study (2013-2017) of trauma patients who presented to our level 1 trauma center emergency department with alcohol intoxication. For each patient, a computed clinical score (CCS) was generated based on the following findings: age ≥50 years, Glasgow Coma Scale <13, evidence of trauma above the clavicles, amnesia, loss of consciousness, headache, vomiting, and seizures. The primary endpoints were NSC, admission, and acute h-CT finding. Univariate and multivariate regressions were used to compare predictors of the primary endpoints. RESULTS: We identified 437 intoxicated trauma patients (median age: 35 years [interquartile range: 25-50]; 71.9% men; median blood alcohol content: 207.8 mg/dL). One hundred and twenty-four (30.4%) patients had acute findings on h-CT, 351 (80.3%) were admitted, and 112 (25.6%) received NSC. On multivariate analysis, CCS was the only predictor of acute h-CT (odds ratio [OR] =1.6; 95% confidence interval [CI]: 1.3-2.0; P < 0.0001) and the best predictor of admission (OR = 1.6; 95% CI: 1.3-1.9; P < 0.0001) and NSC (OR = 1.8; 95% CI: 1.5-2.3; P < 0.0001). CONCLUSIONS: One-third of intoxicated trauma patients have acute findings on h-CT. While the CCS was the best predictor of acute h-CT findings, hospital admission, and NSC, h-CT scanning should continue to be a standard of care.

Perioperative complications of complex abdominal wall reconstruction with biologic mesh: A pooled retrospective cohort analysis of 220 patients from two academic centers.

BACKGROUND: Perioperative outcomes in patients who undergo complex abdominal wall reconstruction (CAWR) may be associated with severe complications, mainly when these procedures are done urgently or emergently. This study aims to identify perioperative predictors of outcomes after CAWR with biologic mesh (BM). MATERIALS AND METHODS: In a retrospective study, perioperative complications (length of hospital stay, ventilator support, surgical site infection, need for wound VAC, reoperation, total complications, and mortality), were analyzed in all patients who underwent open CAWR with BM over six years in two academic centers. Furthermore, we examined the effect of cardiac disease, BMI, diabetes, COPD, case mixed index, hernia size, wound classification, mesh technique, the setting of surgery, on perioperative complications. Multivariable linear and logistic regression analyses were performed. RESULTS: There were 220 patients: 134 patients from center A and 86 patients from center W Mean age was 54.9 ± 14.8 years, 47.7% were females, 33.8% of the patients had BMI ≥30 kg/m2 and median hospital length of stay was 7 days. Center W patients had increased need for mechanical ventilation (10.5% vs. 3%, p = 0.02) and higher need for wound VAC (19.8% vs. 6.7%, p = 0.003). On multivariable linear regression, independent patient predictors of increased hospital length of stay (HLO) were: urgent/emergent surgery (ß 6.93, 95% CI 1.65-12.22, p = 0.01), cardiac disease (ß 7.84, 95% CI 1.23-14.46, p = 0.02) and epigastric defect (ß 13.68, 95% CI 0.29-27.06, p = 0.045). Addition-ally, urgent/emergent setting (OR 3.06, 95% CI 1.69-5.55, p < 0.001) and cardiac disease (OR 2.15, 95% CI 1.03-4.50, p = 0.042) were independently associated with increased odds for perioperative complications. CONCLUSIONS: Perioperative complications of patients undergoing CAWR are considerable and depend on defect complexities, the setting of surgery, comorbidities, wound classification, procedural factors, and case-mix index. Prospective studies on perioperative complications are needed.

Falling Again? Falls in Geriatric Adults-Risk Factors and Outcomes Associated With Recidivism.

BACKGROUND: The elderly population is at increased risk of fall-related readmissions (FRRs). This study is aimed to identify the factors predictive of repeat falls and to analyze the associated outcomes. METHODS: We studied the Nationwide Readmission Database for the year 2010 and identified the patients (≥65 years) who were admitted after falls, and from that subset, further analyzed patients with ≥1 FRRs. Descriptive statistics were used to analyze continuous and categorical variables. Multivariable logistic regression was used to identify predictors of readmission in geriatric patients after controlling for covariates. RESULTS: A total of 358,581 initial fall-related admissions in geriatric adults were identified, and of these, 21,713 experienced ≥1 FRRs (6.06% risk of repeat fall-related admission). Females outnumbered males, and female gender was identified as an independent predictor of FRR (OR 1.10 95% CI 1.07-1.14 P = 0.000). The other independent predictors significantly associated with FRR were age (OR 1.007, 95% CI 1.005-1.009), depression (OR 1.25, 95% CI 1.21-1.30), drug abuse (OR 1.37, 95% CI 1.15-1.63), liver disease (OR 1.25, 95% CI 1.15-1.43, P < 0.001), psychosis (OR 1.16, 95% CI 1.09-1.23), valvular heart disease (OR 1.07, 95% CI 1.02-1.12), chronic pulmonary disease (OR 1.10, 95% CI 1.06-1.13), and number of chronic conditions (OR 1.022, 95% CI 1.016-1.29). Patients admitted emergently or urgently had higher odds of FRR (OR 1.44, 95% CI 1.36-1.52). Hospital demographic was a significant predictor of FRR, as hospitals with bed number >500 was associated with lower odds (OR 0.95, 95% CI 0.92-0.98, P < 0.001). Geriatric patients admitted at nonteaching hospitals and hospitals in large metro areas (population > 1 million) had higher odds of FRR (OR 1.10, 95% CI 1.03 - 1.16) and (OR 1.10, 95% C1 1.07-1.14), respectively. With respect to discharge disposition, patients in the FRR group were less likely to go home (5.9% versus 21.0%) or with home health care (12.6% versus 18.5%), but more likely to be discharged to skilled nursing or intermediate-care facilities (64.1% versus 54.9%) and short-term hospitals (2.8% versus 1.4%). The mortality rate was higher in the FRR group but was not statistically significant (OR 1.06, 95% CI 0.99-1.14). CONCLUSIONS: Given the high burden of fall-related injuries and FRRs to patients and the health care system, it is essential to identify those who are at risk. This study provides a comprehensive list of high-risk predictors as well as the impact on patient outcomes, and hence a chance to intervene for patients with FRRs.

Inpatient burden of esophageal varices in the United States: analysis of trends in demographics, cost of care, and outcomes.

BACKGROUND: Esophageal variceal bleeding remains a common reason for hospitalization in the United States. The main objective of this study was to analyze demographic variations and outcomes in hospitalizations related to esophageal varices (EV) in the US. METHODS: We performed a retrospective observational cohort study using National Inpatient Sample (NIS) database for all hospitalizations with discharge diagnoses of EV, with and without hemorrhage from 2001 to 2011. RESULTS: In 2001, there were 19,167 hospitalizations with discharge diagnoses of EV with and without bleeding compared to 45,578 in 2011 (P<0.001). There was a 138% increase in the number of total EV hospitalizations, a 221% increase in hospitalizations with EV without hemorrhage, and a 7% increase in hospitalizations for patients with EV and hemorrhage. Age group 50-64 was the most affected, accounting for 31.4% of EV hospitalizations in 2001 and 46.7% of EV hospitalizations in 2011 (P<0.001). The overall in-hospital mortality rate was 3.4% for patients with EV without hemorrhage and 8.7% for patients with EV with hemorrhage (P=0.0003). CONCLUSIONS: The number of hospitalizations for patients with asymptomatic EV increased significantly between 2001 to 2011, with only a small concurrent increase in the number of hospitalizations for patients with esophageal variceal bleeding.

The roles of early surgery and comorbid conditions on outcomes of severe necrotizing soft-tissue infections.

PURPOSE: Severe necrotizing soft-tissue infections (NSTIs) require immediate early surgical treatment to avoid adverse outcomes. This study aims to determine the impact of early surgery and comorbid conditions on the outcomes of NSTIs. METHODS: A retrospective cohort study was performed on all subjects presenting with NSTI at an academic medical center between 2005 and 2016. Patients were identified based on ICD codes. Those under the age of 18 or with intraoperative findings not consistent with NSTI diagnosis were excluded. RESULTS: There were 115 patients with a confirmed diagnosis of NSTI with a mean age of 55 ± 18 years; 41% were females and 55% were diabetics. Thirty percent of patients underwent early surgery (< 6 h). There were no significant differences between groups in baseline characteristics. The late group (≥ 6 h) had prolonged hospital stay (38 vs. 23 days, p < 0.008) in comparison to the early group (< 6 h). With every 1 h delay in time to surgery, there is a 0.268 day increase in length of stay, adjusted for these other variables: alcohol abuse, number of debridements, peripheral vascular disease, previous infection and clinical necrosis. Mortality was 16.5%. Multivariable analysis revealed that alcohol abuse, peripheral vascular disease, diabetes, obesity, hypothyroidism, and presence of COPD were associated with an increase in mortality. CONCLUSIONS: Early surgical intervention in patients with severe necrotizing soft-tissue infections reduces length of hospital stay. Presence of comorbid conditions such as alcohol abuse, peripheral vascular disease, diabetes, obesity and hypothyroidism were associated with increased mortality.

Screening for methicillin-resistant Staphylococcus aureus: a comparative effectiveness review.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of health care-associated infections. Although the evidence in support of MRSA screening has been promising, a number of questions remain about the effectiveness of active surveillance. METHODS: We searched the literature for studies that examined MRSA acquisition, MRSA infection, morbidity, mortality, harms of screening, and resource utilization when screening for MRSA carriage was compared with no screening or with targeted screening. Because of heterogeneity of the data and weaknesses in study design, meta-analysis was not performed. Strength of evidence (SOE) was determined using the system developed by the Grading of Recommendations Assessment, Development and Evaluation Working Group. RESULTS: One randomized controlled trial and 47 quasi-experimental studies met our inclusion criteria. We focused on the 14 studies that addressed health care-associated outcomes and that attempted to control for confounding and/or secular trends, because those studies had the potential to support causal inferences. With universal screening for MRSA carriage compared with no screening, 2 large quasi-experimental studies found reductions in health care-associated MRSA infection. The SOE for this finding is low. For each of the other screening strategies evaluated, this review found insufficient evidence to determine the comparative effectiveness of screening. CONCLUSIONS: Although there is low SOE that universal screening of hospital patients decreases MRSA infection, there is insufficient evidence to determine the consequences of universal screening or the effectiveness of other screening strategies.

Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis.

BACKGROUND: The utility of procalcitonin to manage patients with infections is unclear. A systematic review of comparative studies using procalcitonin-guided antibiotic therapy in patients with infections was performed. METHODS: Randomized, controlled trials comparing procalcitonin-guided initiation, intensification, or discontinuation of antibiotic therapy to clinically guided therapy were included. Outcomes were antibiotic usage, morbidity, and mortality. MEDLINE, EMBASE, the Cochrane Database, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990 to December 16, 2011. RESULTS: Eighteen randomized, controlled trials were included. Data were pooled into clinically similar patient populations. In adult intensive care unit (ICU) patients, procalcitonin-guided discontinuation of antibiotics reduced antibiotic duration by 2.05 days (95% confidence interval [CI]: -2.59 to -1.52) without increasing morbidity or mortality. In contrast, procalcitonin-guided intensification of antibiotics in adult ICU patients increased antibiotic usage and morbidity. In adult patients with respiratory tract infections, procalcitonin guidance significantly reduced antibiotic duration by 2.35 days (95% CI: -4.38 to -0.33), antibiotic prescription rate by 22% (95% CI: -41% to -4%), and total antibiotic exposure without affecting morbidity or mortality. A single, good quality study of neonates with suspected sepsis demonstrated reduced antibiotic duration by 22.4 hours (P = 0.012) and reduced the proportion of neonates on antibiotics for ≥ 72 hours by 27% (P = 0.002) with procalcitonin guidance. CONCLUSION: Procalcitonin guidance can safely reduce antibiotic usage when used to discontinue antibiotic therapy in adult ICU patients and when used to initiate or discontinue antibiotics in adult patients with respiratory tract infections.

Treatment of primary and secondary osteoarthritis of the knee.

OBJECTIVES: Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement. DATA SOURCES: We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings. REVIEW METHODS: The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies. RESULTS: Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement. CONCLUSIONS: Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.

Evidence for management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

PURPOSES: This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease. METHODS: The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest. RESULTS: Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality. CONCLUSIONS: PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.

Management of small cell lung cancer.

OBJECTIVES: This is a systematic review of evidence on issues in managing small cell lung cancer (SCLC). Key questions addressed are: the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second- and subsequent-line treatment for relapsed/progressive disease. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Register REVIEW METHODS: The review methods were defined prospectively in a written protocol. We sought randomized controlled trials that compared the interventions of interest. Where randomized trials were limited or nonexistent, we sought additional studies. We performed meta-analysis of studies that compared early and late TRTx. RESULTS: The strongest evidence available for this report is a patient-level meta-analysis showing that PCI improves survival of SCLC patients who achieved complete response following primary therapy from 15.3 percent to 20.7 percent (p=0.01). No other question yielded evidence so robust. The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Our meta-analysis did not find significant reductions in 2- and 3-year mortality for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. For other questions (i.e., management of mixed histology disease; surgery for early limited SCLC), relevant comparative studies were nonexistent. PET may be more sensitive in detecting disease outside the brain than conventional staging modalities, but studies were of poor quality and reliable estimates of performance are not possible. CONCLUSIONS: PCI improves survival among those with a complete response to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components. PET for staging may be useful, but its role awaits clarification by rigorous studies. No relevant evidence was available to address management of mixed histology disease or surgery for early limited SCLC.

Challenges in systematic reviews of diagnostic technologies.

Diagnostic tests are critical components of effective health care. They help determine treatments that are most beneficial for a given patient. Their assessment is a complex process that includes such challenges as a dearth of studies that evaluate clinical outcomes and lack of data on use of the test in realistic clinical settings. The methodologic quality of studies of diagnostic tests also lags behind the quality of studies of therapeutic interventions. Statistical methods to combine diagnostic accuracy data are more complex and not as well developed, leading to difficulties in the interpretation of results. The Agency for Healthcare Research and Quality Technology Assessment Program has adopted a 6-level framework for evaluating diagnostic technologies. The model emphasizes the need for systematic reviews of diagnostic test studies to go beyond the assessment of technical feasibility and accuracy to examine the impact of the test on health outcomes. In this paper, we use examples from 3 Evidence-based Practice Center reports to illustrate 3 challenges reviewers may face when reviewing diagnostic test literature: finding relevant studies, assessing methodologic quality of diagnostic accuracy studies, and synthesizing studies that evaluate tests in different patient populations or use different outcomes.

Chemotherapy sensitivity and resistance assays: a systematic review.

PURPOSE: This systematic review evaluates evidence comparing therapy guided by chemotherapy sensitivity and resistance assays with empiric chemotherapy, emphasizing survival outcomes. METHODS: Prospective studies were sought comparing patients treated contemporaneously by assay-guided chemotherapy and empiric therapy. An initial MEDLINE search and a search performed by a Working Group of the American Society of Clinical Oncology were reviewed with attention to prespecified study selection criteria. RESULTS: This review identified 10 studies meeting selection criteria, plus one retrospective study, using seven different assays. Only two studies randomly assigned patients to assay-guided treatment or empiric treatment. Five of nine nonrandomized studies found significantly higher response rates for patients who received assay-guided therapy compared with those treated empirically. One of the two randomized trials found a significantly higher response rate in the assay-guided group. Four additional studies found response rates favoring assay-guided therapy, but comparisons did not achieve statistical significance. Two nonrandomized studies found overall survival to be significantly improved with assay-guided therapy. One randomized study used a cross-over design that made it difficult to determine whether survival differed between groups, while the other randomized trial found no difference in survival. Six studies provided no comparison of groups on baseline patient characteristics. Only one study reported adverse events data. CONCLUSION: While higher response rates for assay-guided therapy have been observed, differences may be attributable to bias or confounding. Little evidence on survival is available. These results do not establish the relative effectiveness of assay-guided treatment and empiric treatment. Randomized trials are needed.

American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays.

PURPOSE: To develop a technology assessment of chemotherapy sensitivity and resistance assays in order to define the role of these tests in routine oncology practice. METHODS: The American Society of Clinical Oncology (ASCO) established a Working Group to develop the technology assessment. The Working Group collaborated with the Blue Cross and Blue Shield Association (BCBSA) Technology Evaluation Center. The Working Group developed independent criteria for selecting articles for inclusion in the ASCO assessment, and developed a structured data abstraction tool to facilitate review of selected manuscripts. One Working Group member and an ASCO staff member independently reviewed the 1,139 abstracts identified by the BCBSA comprehensive literature search, and by an updated literature search performed by ASCO using the BCBSA search strategy (1966 to January 2004). Of the 12 articles included in this technology assessment, eight were identified by the original BCBSA systematic review, one was provided by industry, and three were identified by the ASCO updated literature review. RESULTS: Review of the literature does not identify any CSRAs for which the evidence base is sufficient to support use in oncology practice. RECOMMENDATIONS: The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient's health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.

Should FDG PET be used to decide whether a patient with an abnormal mammogram or breast finding at physical examination should undergo biopsy?

RATIONALE AND OBJECTIVES: The purpose of this systematic review was to assess the performance of fluorodeoxyglucose positron emission tomography (PET) in the differential diagnosis of benign from malignant lesions among patients with abnormal mammograms or a palpable breast mass and to examine the effects of PET findings on patient care and health outcomes. MATERIALS AND METHODS: A search of the MEDLINE and CancerLit databases covered articles entered between January 1966 and March 2001. Thirteen articles met the selection criteria. Each article was assessed for study quality characteristics. Meta-analysis was performed with a random effects model and a summary receiver operating characteristic curve. RESULTS: A point on the summary receiver operating characteristic curve was selected that reflected average performance, with an estimated sensitivity of 89% and a specificity of 80%. When the prevalence of malignancy is 50%, 40% of all patients would benefit by avoiding the harm of a biopsy with negative biopsy results. The risk of a false-negative result, leading to delayed diagnosis and treatment, is 5.5%. The negative predictive value is 87.9%; thus, the false-negative risk is 12.1%. For a patient with a negative PET scan, a 12% chance of missed or delayed diagnosis of breast cancer is probably too high to make it worth the 88% chance of avoiding biopsy of a benign lesion. CONCLUSION: The evidence does not favor the use of fluorodeoxyglucose PET to help decide whether to perform biopsy. Available studies omit a critical segment of the biopsy population with indeterminate mammograms or nonpalpable masses, for which no conclusions can be reached.