# Gastric Cancer: Surgical Management

## Introduction

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related mortality globally. While incidence has declined in Western countries, it remains highly prevalent in East Asia, Eastern Europe, and South America. Surgery is the only curative treatment for gastric adenocarcinoma, and the extent of resection, adequacy of lymphadenectomy, and integration of perioperative systemic therapy are central to optimizing outcomes. General surgery residents must understand the surgical anatomy, staging, operative techniques, and evidence-based management of this disease.

## Epidemiology and Risk Factors

Helicobacter pylori infection is the strongest risk factor for gastric cancer and is classified as a WHO class I carcinogen; it causes chronic atrophic gastritis and intestinal metaplasia. Dietary factors including high intake of salt-preserved, smoked, and processed foods, nitrosamines, and low fruit and vegetable consumption contribute to risk. Tobacco and alcohol use increase risk independently. Hereditary diffuse gastric cancer is an autosomal dominant condition caused by CDH1 (E-cadherin) germline mutation, carrying a lifetime gastric cancer risk of 70-80%, and prophylactic total gastrectomy is recommended by age 20-30. Other hereditary syndromes associated with gastric cancer include Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome, and Li-Fraumeni syndrome. Precursor lesions include chronic atrophic gastritis, intestinal metaplasia, gastric adenomatous polyps, and prior partial gastrectomy, which confers increased risk 15-20 years after Billroth II reconstruction.

## Histopathologic Classification

### Lauren Classification

The intestinal type consists of well-differentiated, gland-forming tumors associated with H. pylori, intestinal metaplasia, and environmental factors. It is more common in endemic regions, carries a better prognosis, and tends to spread hematogenously. The diffuse type is characterized by poorly differentiated, signet-ring cell morphology with an infiltrative growth pattern known as linitis plastica. It occurs in younger patients with a female predominance, is associated with CDH1 mutations, carries a worse prognosis, and peritoneal dissemination is more common. The mixed type demonstrates features of both intestinal and diffuse types.

### Anatomic Location

Proximal tumors arising in the cardia or gastroesophageal junction are increasing in incidence in Western countries and are classified by the Siewert system: Type I involves the distal esophagus, Type II the true cardia, and Type III the subcardia. Distal tumors in the antral or pyloric region are the most common overall but are decreasing in incidence in developed countries.

## Staging and Preoperative Evaluation

Endoscopy with biopsy is the gold standard for diagnosis, with multiple biopsies (6-8) taken from both the lesion periphery and center. Endoscopic ultrasound is the most accurate modality for T-staging (depth of invasion) and detection of perigastric lymph nodes, with accuracy of 80-90% for T-stage. CT of the chest, abdomen, and pelvis with intravenous and oral contrast is the standard staging study for distant metastases and local extent. PET/CT is useful for detecting occult distant metastases but is less sensitive for diffuse-type and mucinous tumors. Staging laparoscopy with peritoneal cytology is recommended for cT3 or higher or node-positive disease prior to neoadjuvant therapy or definitive resection, as it identifies occult peritoneal disease in 20-30% of patients and changes management accordingly. HER2 testing reveals overexpression in 10-20% of gastric cancers and determines eligibility for trastuzumab in metastatic disease. Microsatellite instability and PD-L1 testing determine immunotherapy eligibility.

<image>Endoscopic and cross-sectional illustration showing the T-staging of gastric cancer from T1a (mucosal invasion) through T4b (invasion of adjacent structures), with corresponding endoscopic ultrasound appearance and relationship to the gastric wall layers including mucosa, submucosa, muscularis propria, and serosa</image>

## Surgical Procedures

### Extent of Gastrectomy

Subtotal (distal) gastrectomy is indicated for distal tumors when a 4-6 cm proximal margin can be achieved. It preserves the gastric remnant and has lower morbidity and better nutritional outcomes than total gastrectomy, while being oncologically equivalent for distal tumors. Total gastrectomy is required for proximal tumors, diffuse-type histology, linitis plastica, and tumors where adequate proximal margins cannot be achieved with subtotal resection. Proximal gastrectomy may be considered for small Siewert Type II/III gastroesophageal junction tumors, though alternatives include extended total gastrectomy or esophagogastrectomy depending on tumor extent. Frozen section of proximal and distal margins is mandatory to confirm R0 resection.

### Lymphadenectomy

| Lymphadenectomy | Stations | Extent | Evidence |
|-----------------|----------|--------|----------|
| D1 | 1–7 | Perigastric nodes only | Minimum standard |
| D2 | 1–12 | D1 + nodes along left gastric, common hepatic, celiac, splenic arteries | Recommended standard (Dutch/UK trials) |
| D3 (para-aortic) | 1–16 | D2 + para-aortic nodes | Not recommended (JCOG9501: no survival benefit) |

D1 lymphadenectomy involves removal of perigastric lymph nodes at stations 1 through 7. D2 lymphadenectomy extends the dissection to include nodes along the left gastric, common hepatic, celiac, and splenic arteries at stations 8 through 12 and is the recommended standard based on evidence from the Dutch and UK trials, which showed improved disease-specific survival with reduced recurrence when performed at experienced centers without pancreaticosplenectomy. A minimum of 15 lymph nodes should be harvested for adequate staging per AJCC guidelines. Extended lymphadenectomy (D3 or para-aortic) is not recommended routinely, as the JCOG9501 trial showed no survival benefit over D2.

### Reconstruction After Gastrectomy

Billroth I (gastroduodenostomy) is a simple reconstruction after distal gastrectomy but is limited by tension and increased bile reflux. Billroth II (gastrojejunostomy) creates a loop gastrojejunostomy with an afferent limb but carries a risk of bile reflux and afferent loop syndrome. Roux-en-Y gastrojejunostomy is the preferred reconstruction after distal gastrectomy because it reduces bile reflux, with a Roux limb typically 40-60 cm in length. Roux-en-Y esophagojejunostomy is the standard reconstruction after total gastrectomy, performed with a circular stapled or hand-sewn anastomosis, and jejunal pouch construction using a Hunt-Lawrence or J-pouch technique may improve capacity and nutritional outcomes.

<image>Surgical illustrations comparing reconstruction techniques after gastrectomy including Billroth I gastroduodenostomy, Billroth II gastrojejunostomy, Roux-en-Y gastrojejunostomy after subtotal gastrectomy, and Roux-en-Y esophagojejunostomy after total gastrectomy with labeled anatomy</image>

## Multimodal Therapy

### Perioperative Chemotherapy

The MAGIC trial (epirubicin, cisplatin, 5-FU) and the FLOT4 trial (docetaxel, oxaliplatin, 5-FU/leucovorin) demonstrated that perioperative chemotherapy given both before and after surgery improves overall survival compared to surgery alone for stage IB-III disease. The FLOT regimen is now the preferred perioperative regimen in the Western world, with median overall survival of 50 months versus 35 months with ECF/ECX in the FLOT4-AIO trial. Neoadjuvant chemotherapy offers advantages including tumor downstaging, treatment of micrometastatic disease, assessment of in vivo chemosensitivity, and improved R0 resection rates.

### Adjuvant Chemoradiation

The INT-0116 (MacDonald) trial demonstrated that adjuvant 5-FU/leucovorin with concurrent radiation improved survival after curative resection, though the benefit may be less after adequate D2 dissection given that the original study population primarily underwent D0 or D1 lymphadenectomy. The CLASSIC trial showed that adjuvant capecitabine/oxaliplatin after D2 gastrectomy improved 3-year disease-free survival from 59% to 74%.

### Immunotherapy

The CheckMate-649 trial demonstrated that nivolumab plus chemotherapy improved overall survival in advanced gastric cancer with PD-L1 CPS of 5 or higher. In the adjuvant setting, nivolumab has been approved as adjuvant therapy after neoadjuvant chemoradiation and R0 resection for gastroesophageal junction cancer based on the CheckMate-577 trial.

## Early Gastric Cancer

Early gastric cancer is defined as tumor confined to the mucosa or submucosa (T1) regardless of lymph node status. Endoscopic resection using endoscopic mucosal resection or endoscopic submucosal dissection is appropriate for well-differentiated, intestinal-type, T1a lesions smaller than 2 cm without ulceration and no lymphovascular invasion. The risk of lymph node metastasis varies by depth: T1a (mucosal) tumors carry a 2-5% risk, while T1b (submucosal) tumors carry a 15-25% risk, and this higher risk mandates surgical resection with lymphadenectomy.

## Complications of Gastrectomy

Anastomotic leak occurs in 3-8% of cases and is higher for esophagojejunostomy than gastrojejunostomy. Diagnosis is made with CT using oral contrast, and management ranges from observation and drainage to reoperation. Dumping syndrome occurs in early (15-30 minutes postprandial with vasomotor symptoms from a rapid hyperosmolar load) and late (1-3 hours postprandial with reactive hypoglycemia) forms, and is managed with dietary modifications including small, frequent, low-carbohydrate meals. Bile reflux gastritis or esophagitis is more common after Billroth II reconstruction, and Roux-en-Y conversion is the definitive treatment. Nutritional deficiencies in iron, calcium, vitamin B12, fat-soluble vitamins, and overall weight loss are expected, with vitamin B12 supplementation mandatory after total gastrectomy. Internal hernias, including Petersen's hernia through the mesenteric defect of the Roux limb and herniation through the jejunojejunostomy mesenteric defect, can be prevented by closing all mesenteric defects at the time of surgery.

## Key Clinical Pearls

Staging laparoscopy with peritoneal cytology is essential before committing to resection in cT3 or higher gastric cancer, as it changes management in up to 30% of patients. D2 lymphadenectomy with a minimum of 15 harvested lymph nodes is the standard of care, and a spleen-preserving technique reduces morbidity. Perioperative FLOT chemotherapy is the current standard for resectable locally advanced gastric cancer in Western practice. CDH1 mutation carriers should undergo prophylactic total gastrectomy, as occult signet-ring cell foci are found in more than 80% of specimens. Roux-en-Y reconstruction minimizes bile reflux and related complications after both subtotal and total gastrectomy.

## References

1. Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4). *Lancet*. 2019;393(10184):1948-1957.
2. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). *Gastric Cancer*. 2021;24(1):1-21.
3. Songun I, Putter H, Kranenbarg EM, et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. *Lancet Oncol*. 2010;11(5):439-449.
4. Blair VR, McLeod M, Carneiro F, et al. Hereditary diffuse gastric cancer: updated clinical practice guidelines. *Lancet Oncol*. 2020;21(8):e386-e397.