Rajini Seevaratnam

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

BackgroundSurgery 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.MethodsSystematic 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.ResultsFor 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.ConclusionsThe 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.

A meta-analysis of D1 versus D2 lymph node dissection

BackgroundSurgery 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.MethodsSystematic 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.ResultsOutcomes 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.ConclusionEarlier 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.

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

BackgroundThere 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.MethodsElectronic 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.ResultsTwenty-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.ConclusionThe 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.

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

BackgroundDespite 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.MethodsElectronic 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.ResultsTwenty-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.ConclusionsDespite 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.

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

BackgroundComplete 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.MethodsA 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.ResultsTwenty-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.ConclusionsThe 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.

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.

Multivisceral resection for gastric cancer: a systematic review

BackgroundThe 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.MethodsElectronic 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.ResultsSeventeen 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.ConclusionsGastrectomy 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.

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

BackgroundThe 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.MethodElectronic 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.ResultsForty 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.ConclusionsPreservation of the spleen and pancreas during extended lymphadenectomy for gastric cancer decreases complications with no clear evidence of improvement or detriment to overall survival.

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

BackgroundComplete 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.PurposeThe 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.MethodsElectronic 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.ResultsFive 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.ConclusionThe 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.