Matthew Dixon

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

BackgroundNodal 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.PurposeWe 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.MethodsSystematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1998 to 2009.ResultsTwenty-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.ConclusionMore 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.

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

BackgroundHereditary 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.MethodsSystematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985 to 2009.ResultsSeventy 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.ConclusionCDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.

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.

Defining Surgical Quality in Gastric Cancer: A RAND/UCLA Appropriateness Study

Savtaj Brar, MD, MSc, Calvin Law, MD, MPH, Robin McLeod, MD, FACS, Lucy Helyer, MD, MSc, Carol Swallow, MD, PhD, FACS, Lawrence Paszat, MD, MSc, Rajini Seevaratnam, MSc, Roberta Cardoso, RN, PhD, Matthew Dixon, MD, Alyson Mahar, MSc, Laercio G Lourenco, MD, Lavanya Yohanathan, MD, Alina Bocicariu, MD, Tanios Bekaii-Saab, MD, Ian Chau, MD, Neal Church, MD, Daniel Coit, MD, FACS, Christopher H Crane, MD, Craig Earle, MD, MSc, Paul Mansfield, MD, FACS, Norman Marcon, MD, Thomas Miner, MD, FACS, Sung Hoon Noh, MD, Geoff Porter, MD, MSc, FACS, Mitchell C Posner, MD, FACS, Vivek Prachand, MD, FACS, Takeshi Sano, MD, PhD, Cornelis van de Velde, MD, PhD, FACS, Sandra Wong, MD, FACS, Natalie Coburn, MD, MPH, FACS

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.

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

BackgroundIn 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.MethodsElectronic 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.ResultsTwenty-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).ConclusionApplication 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.

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

BackgroundThe approach for staging gastric adenocarcinoma (GC) has not been well defined, with heterogeneity in the application of staging modalities.MethodsUtilizing 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.ResultsPretreatment 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.ConclusionsUsing 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.

What provider volumes and characteristics are appropriate for gastric cancer resection? Results of an international RAND/UCLA expert panel

BACKGROUND A relationship between higher volume providers and improved outcomes has been suggested by some studies and has been used to construct guidelines for many diseases. For gastric cancer (GC), however, optimal volume cutoffs are not clear. METHODS A multidisciplinary expert panel of 16 physicians from 6 countries scored 120 scenarios regarding provider characteristics for gastric resections for GC. Appropriateness of scenarios was scored 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 statement similarly. Appropriate scenarios agreed on were scored subsequently for necessity. RESULTS Surgeon and hospital practice volume scenarios were evaluated. The panel felt it was inappropriate for surgeons doing ≤2 GC cases per year to perform a multivisceral resection (MVR), D2 lymphadenectomy (D2-LND), or laparoscopic total gastrectomy, and ≤6 GC cases per year for an MVR involving a pancreatoduodenectomy (MVR-PD), or endoscopic mucosal resections (EMR). It was considered appropriate for surgeons doing ≥11 GC cases per year to perform open gastrectomy or D2-LND, and ≥20 GC cases per year for any MVR, laparoscopic gastrectomy, or EMR. For hospitals, it was considered inappropriate for hospitals managing ≤4 GC cases per year to perform D2-LND or laparoscopic total gastrectomy, and ≤10 GC cases per year, for MVR-PD or EMR. Hospital volumes ≥21 cases per year was considered appropriate for any GC procedure. It was inappropriate for an MVR to be performed in a hospital without interventional radiology services and for a MVR-PD in a hospital with no level I intensive care unit. CONCLUSION Appropriate and inappropriate provider volumes for a variety of gastric procedures have been defined by an international expert panel.

The role of the breast cancer surgeon in personalized cancer care: clinical utility of the 21-gene assay

BACKGROUND Breast cancer surgeons represent the first line of defense for many patients battling this disease. They often have the first contact to discuss treatment options with the patient after diagnosis. However, the potential impact of this consultation has evolved with the arrival of commercialized multigene prognostic and predictive tests that continue to reshape the landscape of breast cancer management, including modern surgical practice. METHOD This review was compiled from peer-reviewed literature indexed in PubMed. CONCLUSIONS The advent of genomic analysis has advanced the treatment and management of breast cancer toward the goal of personalized care. Therefore, the role of the surgeon now extends beyond extirpation of the tumor and includes an understanding of the biology of the disease as well as an appreciation of this new technology. Breast cancer surgeons should seize this opportunity to provide patients and colleagues with this information in an expeditious manner to optimize clinical outcomes.

Optimal management of colorectal liver metastases in older patients: a decision analysis

BACKGROUND Comparative trials evaluating management strategies for colorectal cancer liver metastases (CLM) are lacking, especially for older patients. This study developed a decision-analytic model to quantify outcomes associated with treatment strategies for CLM in older patients. METHODS A Markov-decision model was built to examine the effect on life expectancy (LE) and quality-adjusted life expectancy (QALE) for best supportive care (BSC), systemic chemotherapy (SC), radiofrequency ablation (RFA) and hepatic resection (HR). The baseline patient cohort assumptions included healthy 70-year-old CLM patients after a primary cancer resection. Event and transition probabilities and utilities were derived from a literature review. Deterministic and probabilistic sensitivity analyses were performed on all study parameters. RESULTS In base case analysis, BSC, SC, RFA and HR yielded LEs of 11.9, 23.1, 34.8 and 37.0 months, and QALEs of 7.8, 13.2, 22.0 and 25.0 months, respectively. Model results were sensitive to age, comorbidity, length of model simulation and utility after HR. Probabilistic sensitivity analysis showed increasing preference for RFA over HR with increasing patient age. CONCLUSIONS HR may be optimal for healthy 70-year-old patients with CLM. In older patients with comorbidities, RFA may provide better LE and QALE. Treatment decisions in older cancer patients should account for patient age, comorbidities, local expertise and individual values.