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Previous issues of Current Problems in Surgery reviewing the treatment of patients with gastric cancer were published in 1997 and 2000. What are the important developments since those issues were published? First, staging and histologic classifications have been simplified and unified. The 6th edition of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) staging systems have been unified and universally accepted. The confusion generated by nodal classifications focusing on anatomic nodal basins has been eliminated. Standards of nodal clearance and/or evaluation by the surgical and pathologic team have been established. To stage accurately and optimize survival rates, at least 15 (and preferably 25) lymph nodes must be removed and examined in all patients with gastric cancer. Second, the understanding of the role of H. pylori in the pathogenesis of gastric cancer has matured such that treatment of H. pylori likely will affect the epidemiology of gastric cancer worldwide. Third, accepted standards for the preoperative staging or evaluation of patients with gastric cancer have been published (eg, National Comprehensive Care Network [NCCN] Guidelines). Fourth, multi-institutional studies addressing the extent of nodal dissection and surgical resection in patients with gastric cancer have been published and matured. Although the conclusions of these studies have been debated and “massaged,” there is more consensus on the essentials of surgical treatment of these patients. Fifth, there is finally reason for optimism regarding the nonoperative adjuvant treatment of these patients. Postoperative adjuvant chemoradiotherapy improves survival rates in patients with T2-3 tumors. Recently published studies suggest that effective chemotherapy regimens are available. Finally, it is important to recognize that at least 25% of patients with gastric cancer present with incurable metastatic disease. Although there is a paucity of studies addressing the optimal medical and surgical treatment of this population, the recent literature has added to our understanding of the best palliative care. In 2006, there are fewer indications for palliative surgery. Endoscopic treatments and advances in medical oncology are achieving palliation in many patients.

The incidence of gastric cancer has steadily declined for the last 60 years. Surveillance Epidemiology and End Results (SEER) data indicate that the incidence of gastric cancer in the United States has declined from a rate of 11.7 cases per 100,000 in 1975 to a current rate of 8.8 per 100,000. The precise cause of the overall decline in stomach cancer worldwide is unknown, although it likely represents a change in the environmental factors that play a role in the pathogenesis of cancer of the stomach. There is also a well-documented changing anatomic pattern in the incidence of gastric cancer. Although the incidence of distal cancers has decreased, the incidence of proximal cancers has increased. The development of gastric cancer is a complex process involving environmental factors, host susceptibility, and infection. Risk factors include male gender, family history, pickled foods, diets high in nitrates and salt, and previous gastrectomy. Loss of function or low levels of E-cadherin are present in 50% of diffuse-type stomach cancers.

Clinical and pathologic staging of patients with gastric cancer has been simplified. Staging reliably predicts survival and focuses on the number of positive lymph nodes. The number of positive lymph nodes is the most consistent prognostic indicator of survival (not the location of the positive nodes). The current 5-year survival rates in patients with 1-6, 7-15, and greater than 15 positive nodes are 43%, 21%, and 13%, respectively.

Recent literature has also abandoned unnecessarily complex histologic classification schemes. Using the simple Lauren classification, tumors are designated as intestinal-type or diffuse-type tumors. This classification affects and relates to survival rates, epidemiology, and treatment. Intestinal-type tumors demonstrate a classic progression of carcinogenesis similar to that seen in colon cancer. Initial environmental exposures result in a chronic superficial gastritis. There is then a progression from atrophic gastritis to intestinal metaplasia, dysplasia, and finally cancer. Diffuse-type cancers, on the other hand, do not demonstrate a dysplasia-cancer sequence. They are more common in young and female patients. Decreased function and expression of E-cadherin, a transmembrane protein involved in cell-cell adhesion, is unique to diffuse-type stomach cancer. Gastritis in the adjacent stomach is uncommon.

H. pylori is now known to play a central role in the pathogenesis of gastric cancer and is considered carcinogenic by the World Health Organization (WHO). Meta-analysis of multiple studies calculate an odds ratio of approximately 2 for individuals infected with H. pylori developing gastric cancer. However, H. pylori is 1 of several cofactors. There are regions with high rates of infection but low rates of gastric cancer. For example, 70% to 80% of West Africans are infected with H. pylori, yet gastric cancer is rare, the so-called “African enigma.”

There are virulence factors within strains of H. pylori, such as cytotoxin-associated gene A (cagA) and vaculating toxin A (vacA) that increase the risk of gastric cancer. H. pylori also acts synergistically with nitrates to induce gastric cancer. Eradication of H. pylori may decrease the risk of cancer. Although H. pylori eradication has not been proven to decrease the incidence of gastric cancer in large populations, it has been shown to affect the development of cancer in those patients with precancerous lesions.

Approximately one third of patients with gastric cancer will have elevated levels of CEA and one third will have elevated levels of CA 19-9. The E-cadherin gene is recognized in familial forms of gastric cancer and serum levels of E-cadherin may also be a useful serum marker for disease. In patients with recurrent gastric cancer, it has a sensitivity of 60% and a specificity of 75%.

Computed tomography (CT) scans accurately identify metastatic disease. However, single-slice helical CT does not provide good T staging, with an overall accuracy of only 50%. Multidetector CT (MDCT) is more accurate, with an accuracy of approximately 85%. Recent studies suggest that 3-phase scanning techniques may improve T-staging accuracy to as high as 90%. The accuracy of CT for nodal staging is poor. Magnetic resonance (MR) imaging is comparable or minimally superior to CT in staging gastric cancer. The accuracy of positron emission tomography (PET)/CT in patients with gastric cancer is not well defined. The sensitivity for detecting metastatic disease is approximately 70%, but the reported sensitivity for detecting nodal disease is low (23% to 73%). However, the specificity of PET in the detection of nodal metastasis is high (85%). For reasons that are unclear, PET has poor sensitivity in patients with signet-cell tumors. Preliminary studies suggest that the use of PET/CT in patients presenting with gastric cancer upstages approximately 6% of patients and downstages approximately 9% of patients.

Endoscopic ultrasound (EUS) accurately identifies the T stage in approximately 80% of patients. Differentiating T2 from T3 tumors is the most common problem with EUS. The accuracy of N staging is only approximately 70%. EUS is essential in staging early gastric cancer, identifying those patients with intramucosal carcinomas who are potential candidates for endoscopic mucosal resections.

Laparoscopy is now a vital staging tool in patients with gastric cancer. Laparotomy is avoided in approximately 25% to 30% of patients. Furthermore, metastatic disease distant from the stomach may be detected by laparoscopy, making radiotherapy inappropriate.

Two major cooperative trials, 1 from the Netherlands and 1 from the United Kingdom (the MRC trial) have addressed the role of radical resections in patients with gastric cancer. The Dutch trial and the MRC cooperative trials reported essentially identical results: 5-year survival rates in D1 and D2 patients were approximately 45%; however, major complications were much more likely in D2 patients (43% vs. 25%). Subgroup analysis has shown a strong independent association between resections of the spleen and tail of the pancreas and postoperative death (odds ratios of approximately 5 to 6). Subsequent studies, however, have concluded that splenic-preserving D2 gastrectomies can be performed without increased mortality. Whereas operative mortality was as high as 10% in several centers in the Dutch and MRC trials, current studies suggest that modified D2 resections can be performed with a mortality rate of less than 2%. Follow-up analysis of the Dutch and MRC data suggest that there is a 30% survival advantage for patients with T3 cancers undergoing D2 resections.

Treatment of postoperative complications after operations for gastric cancer has improved. For example, anastomotic leaks can be managed with nonoperative, percutaneous drainage techniques. Novel stenting techniques for managing leaks have been reported. Furthermore, self-expanding stents, other endoscopic palliation techniques, and moderately effective chemotherapy have resulted in a decreasing role for palliative surgery.

Combination drug chemotherapy has advanced significantly in the last decade. The recently published MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial reported a 25% improvement (P = 0.009) in survival in patients randomized to adjuvant combination chemotherapy plus resection versus resection alone.

In Western series, approximately 15% of patients with gastric cancer will have early gastric cancers (EGC). However, in these series, up to 30% of patients have positive lymph nodes and the 5-year survival rate is as low as 68%. Endoscopic mucosal resection (EMR) is indicated in: (1) mucosal tumors; (2) type I, IIa, and IIc EGCs without ulceration; (3) well- or moderately well-differentiated tumors; and (4) tumors smaller than 2 cm. Sentinel lymph node procedures have not been validated and should not be used outside of investigational studies.

The side effects of gastrectomy can be divided into 2 categories: postcibal symptoms and nutritional deficiencies. The net result of these side effects is an average decline in body weight of 10% to 20%. Steatorrhea follows all operations for gastric cancer. The cause of malabsorption is complex but is largely due to digestive imbalance. Bone disease with loss of bone mineral content becomes clinically significant with time in nearly all patients. Replacement regimens should include iron, vitamin B₁₂, calcium, and vitamin D. Bisphosphonate alendronate administration may slow or prevent the development of osteopenia.

In summary, the goal of this article is to provide a practical summary of the current status of the treatment of patients with gastric cancer. It should be a resource that provides the reader with a basic understanding of gastric cancer and also guides treatment decisions in an efficient and optimal manner. Specifically, we have reproduced NCCN guidelines for clinical staging. Laparoscopy is generally accepted to be standard of care in the preoperative evaluation of most patients with gastric cancer. Advances in imaging techniques have further impacted the routine staging. Endoscopic ultrasound and advanced imaging techniques (eg, refined CT technology, MR, and CT/PET scanning) permit the surgeon to tailor the surgical treatment of most patients. Patients with metastatic disease are spared unnecessary laparotomies and/or inappropriate radiotherapy. These staging modalities likely will be instrumental in the design and conduct of impending trials of neoadjuvant treatment.

We have also provided practical information that will improve surgical outcomes. Specific surgical technical maneuvers preferred at our institution are described in detail. To our knowledge, few articles or texts describing the surgical management of patients with gastric cancer make specific recommendations about the perioperative management. How is exposure optimized? Are drains and naso-jejunal tubes placed? Should enteral nutrition be routine? When and how is oral feeding initiated? Unfortunately, surgical dogma guides many of these recommendations. However, we believe that our routine is effective and reproducible in your practice. Furthermore, we do not believe that most surgical texts adequately address the important nutritional consequences of total gastrectomy. Virtually all patients treated for gastric cancer have significant nutritional sequelae and postcibal symptoms. Vitamin deficiencies, decreased bone density, weight loss, and abdominal complaints are routine. Optimal outcomes demand that the treating surgeon prospectively addresses these issues.