Personalized Surgery for Gastric Adenocarcinoma: A Meta-analysis of D1 versus D2 Lymphadenectomy.

BACKGROUND: The recent publication of 5-year survival data for the Italian Gastric Cancer Study Group (IGCSG) D1 versus D2 lymphadenectomy for gastric cancer trial adds important data for analysis of whether a D2 lymphadenectomy improves survival. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985 to February 1, 2014. Meta-analyses were performed using RevMan version 5 software. Long-term outcomes were analyzed. Subgroup analyses of T and N stage were performed. RESULTS: Outcomes of four randomized, controlled trials involving 1,599 patients (823 D1: 776 D2) enrolled from 1982 to 2005 were included for qualitative analysis and quantitative meta-analysis. Despite the addition of long-term survival data from the IGCSG, 5-year overall and nodal status survival was similar between D1 and D2 trials. However, subgroup analysis revealed a survival benefit for T3 patients (odds ratio 1.64, 95 % confidence interval 1.01-2.67) and a trend for survival benefit for advanced nodal stage (odds ratio 1.36, 95 % confidence interval 0.98-1.87) with D2 compared with D1 lymphadenectomy. CONCLUSIONS: As recent studies have demonstrated comparable short-term surgical outcomes for both D1 and D2 lymphadenectomies, consideration should be made for more extensive lymph node dissection among patients with advanced stage.

Optimal management of gastric cancer: results from an international RAND/UCLA expert panel.

OBJECTIVE: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. METHODS: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. RESULTS: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. CONCLUSIONS: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.

What studies are appropriate and necessary for staging gastric adenocarcinoma? Results of an international RAND/UCLA expert panel.

BACKGROUND: The approach for staging gastric adenocarcinoma (GC) has not been well defined, with heterogeneity in the application of staging modalities. METHODS: Utilizing a RAND/UCLA appropriateness methodology (RAM), a multidisciplinary expert panel of 16 physicians scored 84 GC staging scenarios. Appropriateness was scored from 1 to 9. Median appropriateness scores from 1 to 3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 or more of 16 panelists scored the scenario similarly. Appropriate scenarios were subsequently scored for necessity. RESULTS: Pretreatment TNM stage determination is necessary. Necessary staging maneuvers include esophagogastroduodenoscopy (EGD); biopsy of the tumor; documentation of tumor size, description, location, distance from gastroesophageal junction (GEJ), and any GEJ, esophageal, or duodenal involvement; if an EGD report is unclear, surgeons should repeat it to confirm tumor location. Pretreatment radiologic assessment should include computed tomography (CT)-abdomen and CT-pelvis, performed with multidetector CT scanners with 5-mm slices. Laparoscopy should be performed before resection of cT3-cT4 lesions or multivisceral resections. Laparoscopy should include inspection of the stomach, diaphragm, liver, and ovaries. CONCLUSIONS: Using a RAM, we describe appropriate and necessary staging tests for the pretreatment staging evaluation of GC, as well as how some of these staging maneuvers should be conducted.

A RAND/UCLA appropriateness study of the management of familial gastric cancer.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG). METHODS: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity. RESULTS: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older. CONCLUSIONS: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.

A systematic review of the indications for genetic testing and prophylactic gastrectomy among patients with hereditary diffuse gastric cancer.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome specifically associated with germline mutations to the E-cadherin (CDH1) gene. HDGC is characterized by autosomal dominance and high penetrance and a high cumulative risk for advanced gastric cancer. Our purpose in this study was to identify and synthesize findings from all articles on: (1) current recommendations for CDH1 screening and prophylactic gastrectomy; (2) CDH1 testing results in HDGC patients; and (3) prophylactic gastrectomy results in HDGC patients. METHODS: Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985 to 2009. RESULTS: Seventy articles were included in this review. Among patients with a positive family history of gastric cancer, 1085 were screened from 454 families, and 38.4% tested positive. Mutation-positive families also had a considerable family history of breast and colon cancer. Of the 322 patients screened for CDH1 mutations by current HDGC screening criteria, 29.2% tested positive. Among the 76.8% of patients who underwent prophylactic gastrectomy following positive CDH1 test results, 87.0% had positive final histopathology results and 64.6% had signet ring cells identified. Some of the patients with negative final histopathology results had opted to undergo prophylactic gastrectomy prior to CDH1 testing, and were ultimately found to be negative for CDH1 mutations. CONCLUSION: CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.

A meta-analysis of D1 versus D2 lymph node dissection.

BACKGROUND: Surgery is the only curative treatment for patients with gastric cancer. However, the extent of lymph node dissection is still debated. Therefore, with the publication of newer trial results, we conducted an updated meta-analysis of D1 versus D2 randomized controlled trials comparing outcomes. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985, to December 31, 2010. Meta-analyses were performed using RevMan v5 software. Both short- and long-term outcomes were analyzed. Subgroup analyses of T stage and spleen/pancreas resection versus preservation were performed. RESULTS: Outcomes of 5 randomized trials involving 1642 patients (845 D1, 797 D2) enrolled from 1982 to 2005 were included. Despite the addition of the more recent trials, overall hospital mortality and reoperation rates were still higher in D2 cases. Subgroup analysis of recent trials and spleen/pancreas preservation revealed no significant difference in hospital mortality between groups. Five-year overall survival was similar between D1 versus D2 trials. Sub-analysis by tumor depth and spleen/pancreas preservation detected trends for improved survival with D2 lymphadenectomy in T3/T4 patients and those with spleen/pancreas preservation. CONCLUSION: Earlier trials show that D2 dissections have higher operative mortality, while recent trials have similar rates. A trend of improved survival exists among D2 patients who did not undergo resection of the spleen or pancreas, as well as for patients with T3/T4 cancers.

Systematic review of the predictors of positive margins in gastric cancer surgery and the effect on survival.

BACKGROUND: Complete resection is the only definitive treatment available for gastric cancer. Factors associated with positive margins and their survival effects have been the subject of many studies, but the appropriate management for these patients is still debated. The objective of this review is to examine positive margins after gastric cancer resections by exploring predictive factors, impact on survival, and optimal strategies for re-resection. METHODS: A systematic electronic literature search was conducted using Medline and EMBASE from January 1, 1998, to December 31, 2009. Studies on gastric or gastroesophageal junction adenocarcinoma that either investigated the predictors for positive margin or employed multivariate methods to analyze the survival effects of positive margins were selected. RESULTS: Twenty-two studies incorporating 19355 patients were included in this review. Positive margins were associated with larger tumor size, deeper wall penetration, more extensive gastric involvement, greater nodal involvement, higher stage, diffuse histology, higher Borrmann type, lymphatic vessel involvement, and total gastrectomy. Patient survival was independently associated with margin status, and this survival effect was more prominent in early cancers in most studies that performed subgroup analyses. CONCLUSIONS: The probability of acquiring positive margins is highly dependent on the biology and the extent of the tumor. There is a significant negative effect on survival, which is more prominent in cancers at early stages, making re-resection or a second operation important. Patients with more advanced disease can be offered more extensive surgery to remove disease, but this should be balanced against the risks of more extensive resections.

A systematic review of patient surveillance after curative gastrectomy for gastric cancer: a brief review.

BACKGROUND: Complete resection of a gastric cancer and adjacent lymph nodes offers the only chance for cure of the disease. However, disease recurrence occurs in 22-51% of cases, and its prognosis is very poor. Many clinicians perform post-operative follow-up for these patients, although there is no consensus on the regimen, frequency of visits, mode of testing, or the rationale of a follow-up program. PURPOSE: The objective of this systematic review was to identify the evidence for surveillance in patients with resected gastric cancer, specifically examining the interval of follow-up and the modalities utilized. METHODS: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1st 1998 to December 1st 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. RESULTS: Five articles were selected. A total of 810 patients underwent post-operative follow-up. History and physical examination, hematological and chemistry profile, endoscopy (esophagogastroduodenoscopy [EGD]), and computed tomography (CT) were the most frequently employed modalities. CT detected the majority of recurrences in the included studies. The survival post-recurrence was significantly higher in the asymptomatic group compared with symptomatic group in three studies, but this may simply reflect lead-time bias. No differences in overall survival (OS) were found. CONCLUSION: The included studies failed to show an improvement in OS with more intense surveillance. Further prospective studies are required to determine whether a subgroup of patients may benefit from more intensive follow-up.

Multivisceral resection for gastric cancer: a systematic review.

BACKGROUND: The overall prognosis and survival of patients with advanced gastric cancer is generally poor. One of the most powerful predictors of outcomes in gastric cancer surgery is an R0 resection. However, the extent of the required surgical resection and the additional benefit of multivisceral resection (MVR) are controversial. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. RESULTS: Seventeen studies were included in this review. Among the 1343 patients who underwent MVR, overall complication rates ranged from 11.8 to 90.5%. Perioperative mortality was found to be 0-15%. Pathological T4 disease was confirmed in 28.8-89% of patients. R0 resection and extent of nodal involvement were important predictors of survival in patients undergoing MVR. Patient outcomes may also be affected by the number of organs resected. CONCLUSIONS: Gastrectomy with MVR can be safely pursued in patients with locally advanced gastric cancer to achieve an R0 resection. MVR may not be beneficial in patients with extensive nodal disease.

Systematic review of pancreaticoduodenectomy for locally advanced gastric cancer.

BACKGROUND: The purpose of this study was to identify and synthesize findings from all articles on surgical and long-term outcomes in patients with gastric cancer undergoing gastrectomy combined with pancreaticoduodenectomy (PD). METHODS: Electronic literature searches were conducted using Medline, EMBASE, and Cochrane databases from January 1, 1985, to December 31, 2009. RESULTS: Eight retrospective case series were included, with 132 patients having PD combined with gastrectomy. PD was combined with total gastrectomy in 27 patients, and subtotal gastrectomy in 81 patients; 24 patients had undocumented gastric resection type. Clinical stage was available for 92 patients (4 stage I, 7 stage II, 26 stage III, and 55 stage IV). Five studies (98 patients having PD combined with gastrectomy) compared PD and gastrectomy to gastrectomy alone. In the four studies reporting morbidity, PD had a higher morbidity. The pooled pancreatic anastomotic leak rate was 24.5% for the seven studies in which complications were reported; however, there were no peri-operative deaths. Long-term survival (37.3% at 5 years) in gastric cancer patients with PD combined with gastrectomy was described; however, survival was poor in the setting of incurable factors. Due to heterogeneity of patients and staging techniques in the case series no recommendations can be made on the appropriate selection criteria for patients undergoing PD and gastrectomy. CONCLUSION: PD for gastric cancer invading the pancreas is associated with a higher morbidity; given the heterogeneous data, defining exact selection criteria is difficult.

A systematic review of spleen and pancreas preservation in extended lymphadenectomy for gastric cancer.

BACKGROUND: The overall prognosis and survival of patients with advanced gastric cancer are generally poor. Extended lymphadenectomy is recommended for patients with advanced gastric cancer; however, splenectomy and distal pancreatectomy performed with an extended lymph node dissection may be associated with increased morbidity and mortality. METHOD: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 31 December 2009. Studies on gastric carcinoma investigating extended lymphadenectomy with splenectomy and/or pancreaticosplenectomy that reported data on surgical outcomes or survival were selected. RESULTS: Forty studies were included in this review. Decreased complication rates were demonstrated with spleen preservation in two prospective studies and three retrospective studies, and with pancreas preservation in five retrospective studies. No randomized controlled trial showed survival benefit or detriment for preservation of spleen or pancreas in extended lymphadenectomy. Improved survival was demonstrated with spleen preservation in two prospective and eight retrospective studies, and with pancreas preservation in one prospective and four retrospective studies. CONCLUSIONS: Preservation of the spleen and pancreas during extended lymphadenectomy for gastric cancer decreases complications with no clear evidence of improvement or detriment to overall survival.

What is the accuracy of sentinel lymph node biopsy for gastric cancer? A systematic review.

BACKGROUND: In gastric cancer, the utility of sentinel lymph node (SLN) biopsy has not been established. SLN may be a good predictor of the pathological status of other lymph nodes and thus the necessity for more extensive surgery or lymph node dissection. We aimed to identify and synthesize findings on the performance of SLN biopsies in gastric cancer. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. Titles and abstracts were independently rated for relevance by a minimum of two reviewers. Techniques, detection rates, accuracy, sensitivity, specificity, and false-negative rates (FNRs) were analyzed. Analysis was performed based on the FNR. RESULTS: Twenty-six articles met our inclusion criteria. SLN detection using the dye method (DM) was reviewed in 18 studies, the radiocolloid method (RM) was used in 12 studies, and both dye and radiocolloid methods (DUAL) were used in 5 studies. The DM had an overall calculated FNR of 34.7% (95% confidence interval [CI] 21.2, 48.1). The RM had an overall calculated FNR of 18.5% (95% CI 9.1, 28.0). DUAL had an overall calculated FNR of 13.1% (95% CI -0.9, 27.2). CONCLUSION: Application of the SLN technique may be practical for early gastric cancer. The use of DUAL for identifying SLN may yield a lower FNR than either method alone, although statistical significance was not met.

A systematic review and meta-analysis of the utility of EUS for preoperative staging for gastric cancer.

BACKGROUND: Accurate preoperative staging is important in determining the appropriate treatment of gastric cancer. Recently, endoscopic ultrasound (EUS) has been introduced as a staging modality. However, reported test characteristics for EUS in gastric cancer vary. Our purpose in this study was to identify, synthesize, and evaluate findings from all articles on the performance of EUS in the preoperative staging of gastric cancer. METHODS: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 1 December 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Meta-analysis for the performance of EUS was analyzed by calculating agreement (Kappa statistic), and pooled estimates of accuracy, sensitivity, and specificity for all EUS examinations, using histopathology as the reference standard. Subgroup analyses were also performed. RESULTS: Twenty-two articles met our inclusion criteria and were included in the review. EUS pooled accuracy for T staging was 75% with a moderate Kappa (0.52). EUS was most accurate for T3 disease, followed by T4, T1, and T2. EUS pooled accuracy for N staging was 64%, sensitivity was 74%, and specificity was 80%. There was significant heterogeneity between the included studies. Subgroup analyses found that annual EUS volume was not associated with EUS T and N staging accuracy (P = 0.836, 0.99, respectively). CONCLUSION: EUS is a moderately accurate technique that seems to describe advanced T stage (T3 and T4) better than N or less advanced T stage. Stratifying by EUS annual volume did not affect EUS performance in staging gastric cancer.

A systematic review of the accuracy and indications for diagnostic laparoscopy prior to curative-intent resection of gastric cancer.

BACKGROUND: Despite improved preoperative imaging techniques, patients with incurable or unresectable gastric cancer are still subjected to non-therapeutic laparotomy. Diagnostic laparoscopy (DL) has been advocated by some to be essential in decision-making in gastric cancer. We aimed to identify and synthesize findings on the value of DL for patients with gastric cancer, in this era of improved preoperative imaging. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We calculated the change in management and avoidance of laparotomy based on the addition of DL and laparoscopic ultrasound (LUS). The accuracy, agreement (kappa), sensitivity, and specificity of DL in assessing tumor extent, nodal involvement, and the presence of metastases with respect to the gold standard (pathology) were also calculated. RESULTS: Twenty-one articles were included. DL showed moderate to substantial agreement with final pathology for T stage, but only fair agreement for N stage. For M staging, DL had an overall accuracy, sensitivity, and specificity ranging from 85-98.9%, 64.3-94%, and 80-100%, respectively. The use of DL altered treatment in 8.5-59.6% of cases, avoiding laparotomy in 8.5-43.8% of cases. LUS provided additional benefit in 5.8-7.2% of cases. CONCLUSIONS: Despite evolving preoperative imaging techniques, diagnostic laparoscopy continues to be of substantial value in staging patients with gastric cancer and in avoiding unnecessary laparotomy. The current data support DL for all patients with advanced gastric cancer.

A systematic review of the accuracy and utility of peritoneal cytology in patients with gastric cancer.

BACKGROUND: There is lack of uniformity in the utilization of peritoneal cytology in gastric cancer management. The identification of intraperitoneal free cancer cells (IFCCs) is believed to confer poor prognosis. However, while some of these patients are palliated, others may undergo more aggressive therapies. In this review, we aimed to identify and synthesize findings on the use of peritoneal cytology in predicting peritoneal recurrence and overall survival in curative gastric cancer patients. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We determined the accuracy, sensitivity, and specificity of peritoneal cytology in predicting peritoneal recurrence based on four techniques-conventional cytology, immunoassay, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Recurrence rates and overall survival rates for curative patients were determined, based on positivity or negativity for IFCCs. RESULTS: Twenty-eight articles were included. All four techniques showed wide variations in accuracy, sensitivity, and specificity in predicting peritoneal recurrence. Recurrence rates for patients positive for IFCCs ranged from 11.1 to 100%, while those negative for IFCCs had recurrence rates of 0-51%. Overall survival was significantly reduced for patients with positive IFCCs. Short follow-up periods and possible duplication of results may limit result interpretation. CONCLUSION: The presence of IFCCs appears to increase the risk of peritoneal recurrence and is associated with worse overall survival in gastric cancer patients. Further incorporation of peritoneal cytology in clinical decision-making in gastric cancer depends on the development of a consistently accurate and rapid IFCC detection method.

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis.

BACKGROUND: Surgery is the fundamental curative option for gastric cancer patients. Imaging scans are routinely prescribed in an attempt to stage the disease prior to surgery. Consequently, the correlation between radiology exams and pathology is crucial for appropriate treatment planning. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009. We calculated the accuracy, overstaging rate, understaging rate, Kappa statistic, sensitivity, and specificity for abdominal ultrasound (AUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) with respect to the gold standard (pathology). We also compared the performance of CT by detector number and image type. A meta-analysis was performed. RESULTS: For pre-operative T staging MRI scans had better performance accuracy than CT and AUS; CT scanners using ≥ 4 detectors and multi-planar reformatted (MPR) images had higher staging performances than scanners with <4 detectors and axial images only. For pre-operative N staging PET had the lowest sensitivity, but the highest specificity among modalities; CT performance did not significantly differ by detector number or addition of MPR images. For pre-operative M staging performance did not significantly differ by modality, detector number, or MPR images. CONCLUSIONS: The agreement between pre-operative TNM staging by imaging scans and post-operative staging by pathology is not perfect and may affect treatment decisions. Operator dependence and heterogeneity of data may account for the variations in staging performance. Physicians should consider this discrepancy when creating their treatment plans.

How many lymph nodes should be assessed in patients with gastric cancer? A systematic review.

BACKGROUND: Nodal status is one of the most important prognostic factors in gastric adenocarcinoma (GC). As such, it is important to assess an appropriate number of lymph nodes (LNs) in order to accurately stage patients. However, the number of LNs assessed in each GC case varies, and in many cases the number examined per gastric specimen is less than current recommendations. PURPOSE: We aimed to identify and synthesize findings from all articles evaluating the association of clinicopathological features and long-term outcomes with the number of LNs assessed among GC patients. METHODS: Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. RESULTS: Twenty-five articles were included in this review. Extensive resection, increased tumor size, and greater TNM staging were all associated with a greater number of LNs assessed. The disease-free survival was longer and recurrence rate was lower in patients with more LNs assessed. Overall survival, as well as survival by TNM and clinical stage, was improved among patients with an increased number of LNs assessed, but much of this appears to be due to stage migration, with the effect more pronounced in more advanced disease. CONCLUSION: More LNs assessed resulted in less stage migration and possibly better long-term outcomes. Although current guidelines suggest 16 LNs to be assessed, especially in advanced GC, a higher number of LNs should be assessed.

Diagnostic Performance of a Novel Three-Dimensional Neuroretinal Rim Parameter for Glaucoma Using High-Density Volume Scans.

PURPOSE: To evaluate the diagnostic performance of a 3-dimensional (3D) neuroretinal rim parameter, the minimum distance band (MDB), using optical coherence tomography (OCT) high-density volume scans for open-angle glaucoma. DESIGN: Reliability analysis. METHODS: setting: Institutional. STUDY POPULATION: Total of 163 patients (105 glaucoma and 58 healthy subjects). OBSERVATION PROCEDURES: One eye of each patient was included. MDB and retinal nerve fiber layer (RNFL) thickness values were determined for 4 quadrants and 4 sectors using a spectral-domain OCT device. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivities, specificities, and positive and negative predictive values. RESULTS: The best AUROC values of 3D MDB thickness for glaucoma and early glaucoma were for the overall globe (0.969, 0.952), followed by the inferior quadrant (0.966, 0.949) and inferior-temporal sector (0.966, 0.944), and then followed by the superior-temporal sector (0.964, 0.932) and superior quadrant (0.962, 0.924). All 3D MDB thickness AUROC values were higher than those of 2D RNFL thickness. Pairwise comparisons showed that the diagnostic performance of the 3D MDB parameter was significantly better than 2D RNFL thickness only for the nasal quadrant and inferior-nasal and superior-nasal sectors (P = .023-.049). Combining 3D MDB with 2D RNFL parameters provided significantly better diagnostic performance (AUROC 0.984) than most single MDB parameters and all single RNFL parameters. CONCLUSIONS: Compared with the 2D RNFL thickness parameter, the 3D MDB neuroretinal rim thickness parameter had uniformly equal or better diagnostic performance for glaucoma in all regions and was significantly better in the nasal region.

Processes of care in the multidisciplinary treatment of gastric cancer: results of a RAND/UCLA expert panel.

IMPORTANCE: There is growing interest in reducing the variations and deficiencies in the multidisciplinary management of gastric cancer. OBJECTIVE: To define optimal treatment strategies for gastric adenocarcinoma (GC). DESIGN, SETTING, AND PARTICIPANTS: RAND/UCLA Appropriateness Method involving a multidisciplinary expert panel of 16 physicians from 6 countries. INTERVENTIONS: Gastrectomy, perioperative chemotherapy, adjuvant chemoradiation, surveillance endoscopy, and best supportive care. MAIN OUTCOMES AND MEASURES: Panelists scored 416 scenarios regarding treatment scenarios for appropriateness from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores from 1 to 3 were considered inappropriate; 4 to 6, uncertain; and 7 to 9, appropriate. Agreement was reached when 12 of 16 panelists scored the scenario similarly. Appropriate scenarios agreed on were subsequently scored for necessity. RESULTS: For patients with T1N0 disease, surgery alone was considered appropriate, while there was no agreement over surgery alone for patients T2N0 disease. Perioperative chemotherapy was appropriate for patients who had T1-2N2-3 or T3-4 GC without major symptoms. Adjuvant chemoradiotherapy was classified as appropriate for T1-2N1-3 or T3-4 proximal GC and necessary for T1-2N2-3 or T3-4 distal GC. There was no agreement regarding surveillance imaging and endoscopy following gastrectomy. Surveillance endoscopy was deemed to be appropriate after endoscopic resection. For patients with metastatic GC, surgical resection was considered inappropriate for those with no major symptoms, unless the disease was limited to positive cytology alone, in which case there was disagreement. CONCLUSIONS AND RELEVANCE: Patients with GC being treated with curative intent should be considered for multimodal treatment. For patients with incurable disease, surgical interventions should be considered only for the management of major bleeding or obstruction.

Comparison of total protein concentration in skeletal muscle as measured by the Bradford and Lowry assays.

The Lowry and Bradford assays are the most commonly used methods of total protein quantification, yet vary in several aspects. To date, no comparisons have been made in skeletal muscle. We compared total protein concentrations of mouse red and white gastrocnemius, reagent stability, protein stability and range of linearity using both assays. The Lowry averaged protein concentrations 15% higher than the Bradford with a moderate correlation (r = 0.36, P = 0.01). However, Bland-Altman analysis revealed considerable bias (15.8 +/- 29.7%). Both Lowry reagents and its protein-reagent interactions were less stable over time than the Bradford. The linear range of concentration was smaller for the Lowry (0.05-0.50 mg/ml) than the Bradford (0-2.0 mg/ml). We conclude that the Bradford and Lowry measures of total protein concentration in skeletal muscle are not interchangeable. The Bradford and Lowry assays have various strengths and weaknesses in terms of substance interference and protein size. However, the Bradford provides greater reagent stability, protein-reagent stability and range of linearity, and requires less time to analyse compared to the Lowry assay.