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Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Worldwide, gastric cancer was once the most common malignancy; it currently ranks as the fifth most common cancer (following lung, breast, colorectal, and prostate cancer) and the third most common cause of cancer deaths in both sexes.[1] In the United States, gastric cancer was the leading cause of cancer mortality in the early to mid 20th century[2]; since then, however, its incidence and associated mortality have decreased significantly.[3]
A few of the most important reasons for these dramatic shifts include the following:
Successful treatment of Helicobacter pylori infection, leading to a reduction of chronic atrophic gastritis, an inflammatory precursor of cancer[4]
Widespread adoption of refrigeration, which led to decreased consumption of preserved foods[5]
Increased dietary intake of vegetables, which contain antioxidants presumed to decrease the risk of cancer[6]
Nonetheless, gastric cancer remains an important health issue, owing to the lack of good, noninvasive screening tests for asymptomatic individuals[7,8] and because many cases are diagnosed in the late stages of the disease, which generally leads to poor outcomes.[8-10]
The image shows gastric adenocarcinoma viewed endoscopically.
Adapted image courtesy of the NCI/Surveillance, Epidemiology, and End Results (SEER) Program.[3]
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Incidence and Mortality
The International Agency for Research on Cancer (IARC) estimates there were approximately 1 million new cases of gastric cancer in 2012, with over 70% of the cases occurring in developing countries.[1] Half of the total cases worldwide—and the highest estimated mortality rates—were in Eastern Asia alone (predominantly China), with men affected about twice as often as women. Regions with high mortality in both sexes from gastric cancer include Central and Eastern Europe as well as Central and South America.[1]
In the US, gastric cancer is the 14th most common cancer type, with approximately 26,240 new cases and 10,800 deaths expected in 2018, representing approximately 1.7% of all cancer cases and 1.8% of cancer deaths.[8] Data from 2012 to 2014 indicate that about 0.8% of men and women will be diagnosed with gastric cancer in their lifetime.[3]
Laparoscopic image courtesy of N Joseph Espat, MD.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Previously, most gastric carcinomas were found in the antrum; in recent decades, the incidence of antral neoplasms has decreased, whereas the trend for lesions at the gastric cardia has remained stable or increased.[9,11] About 10% of patients with gastric cancer present with a tumor that involves the entire stomach[12]; this rare condition is known as linitis plastica or "leather bottle" stomach (shown).[11,12]
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Risk Factors
Although the exact cause of gastric cancer remains unclear, known predisposing risk factors include the following[8,9]:
H pylori infection and chronic atrophic gastritis
Male sex
Advanced age
Low dietary intake of fruits and vegetables
High dietary intake of smoked, salted, and preserved foods
Pernicious anemia
Overweight/obesity
Tobacco use
Certain hereditary syndromes (eg, familial adenomatous polyposis [FAP], hereditary nonpolyposis colon cancer [HNPCC], Peutz-Jeghers syndrome [PJS])
Family history of gastric cancer
Menetrier disease (giant hypertrophic gastritis)
Occupation in the coal, metal, and rubber industries
Being an ethnic immigrant from countries with high rates of gastric cancer
The image shows the en face view of an ulcer on the lesser curvature in a subtotal gastrectomy specimen from a patient with gastric adenocarcinoma. The pyloric margin is to the left.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Classification
Gastric cancers are a heterogeneous group of lesions[10,13]; 90%-95% are adenocarcinomas[8,9] that arise from the mucus-producing rather than acid-producing cells of the gastric mucosa. The remaining gastric malignancies include lymphomas, carcinoid tumors, gastrointestinal stromal tumors (GISTs), leiomyosarcomas, small cell carcinomas, and squamous cell carcinomas.[8]
The image shows a longitudinal cut in the plane of the lesser curvature from the same gross specimen as in the previous slide. The pyloric margin is to the left. Note the presence of several prominent nodes of the lesser omentum, these contained metastatic cancer.
Adapted image of gastric signet ring cell carcinoma under very high magnification (hematoxylin and eosin [H&E] stain) courtesy of Wikimedia Commons/Nephron.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
The Lauren and the World Health Organization (WHO) histologic classification systems are two widely used systems for categorizing gastric cancers.
The Lauren classification uses distinct clinical and pathologic features to subdivide gastric cancers into intestinal adenocarcinomas (about 54%), diffuse adenocarcinomas (about 32%), indeterminate, and mixed.[9,13,14] The intestinal type is usually well to moderately differentiated and associated with metaplasia or chronic gastritis[13]; it occurs more often in men and older individuals.[15] The diffuse type typically lacks organized gland formation, is usually poorly differentiated, has many signet ring cells, and carries a worse prognosis; females and young individuals appear to be more frequently affected.[13,15,16] If more than 50% of the tumor contains intracytoplasmic mucin, it is designated as signet ring type (shown); signet ring cells are filled with mucin vacuoles that push the nucleus to one side (inset).
The WHO classification categorizes gastric cancers on the basis of their histomorphologic appearance, with four major types: tubular, papillary, mucinous, and poorly cohesive (eg, signet ring cell carcinoma).[13]
Image of metastatic gastric cancer to the umbilicus or "Sister Mary Joseph Sign", courtesy of Abdul Saied, MD.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Presentation
Patients with early-stage gastric cancer may be asymptomatic, or they may have vague and nonspecific signs/symptoms that can simulate those of peptic ulcer disease; these factors may contribute to delays in the diagnosis and explain why only about 20% of gastric malignancies are found at an early stage.[8] Signs/symptoms generally appear with advanced disease; patients most often present with epigastric discomfort, but anemia, weight loss, anorexia, and/or upper GI bleeding can also occur.[8]
The physical examination findings are usually unremarkable unless advanced disease is present, in which case an abdominal mass and enlarged lymph nodes may be found. Most of the findings associated with gastric carcinoma are secondary to lymph node involvement. The Virchow sign or node is the presence of a hard, enlarged lymph node in the left supraclavicular fossa; the "Sister Mary Joseph" lymph node (shown) is a firm nodule in the umbilicus; and the "Irish node" is an enlarged left axillary lymph node.[17,18] Malignant ascites may also be present in advanced disease (18.3%).[19]
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Workup
Perform a detailed history and physical examination.[20] Laboratory studies include a complete blood count (CBC), comprehensive chemistry panel, and liver function studies.[18,20] If metastasis is suspected, the National Comprehensive Cancer Network (NCCN) recommends obtaining tests for human epidermal growth factor receptor 2/neu (HER2-neu) protein expression.[20]
Endoscopy
Endoscopy is considered the best diagnostic modality to evaluate patients with a suspected gastric malignancy.[8,9,18] This study allows direct visualization of the gastric mucosa, precise localization of the lesion, and tissue sampling; it can also be combined with endoscopic ultrasonography (EUS) to more accurately define the depth of tumor invasion through the gastric wall and for assessment of perigastric lymph nodes.[18]
EUS is highly accurate in assessing the depth of tumor invasion (75%-85%); however, it is less accurate in determining lymph node status (50%-80%).[18,20,21] This modality also allows tissue sampling from suspicious, enlarged lymph nodes.
The white arrows in the image indicate invasive gastric adenocarcinoma.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Staging
Once the lesion has been identified by endoscopy and the diagnosis has been confirmed by tissue biopsy, staging follows.
The most commonly used staging classification in the Western Hemisphere is the American Joint Committee on Cancer's (AJCC's) tumor, node, and metastasis (TNM) classification system.[8,9,18,20] It aids clinicians in determining the next best step in management and is proposed as a surrogate of prognosis.[8,18,20] In the Eastern Hemisphere, the Japanese classification system is commonly used; it is more detailed than the AJCC TNM system and is based on anatomic involvement, with particular focus on lymph node stations.[22]
Clinical staging takes place before surgery and is made on the basis of clinical findings and the use of imaging studies such as EUS, computed tomography (CT) scanning, and positron emission tomography (PET) scanning.[8,18,20] Routine chest radiographs may help to rule out metastasis. If surgical intervention is undertaken, pathologic staging can be achieved from tissue/organ samples.[8,18,20]
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Computed tomography scanning
CT scanning is the most commonly used initial study for preoperative staging[20] to detect perigastric, regional, and/or distant lymphadenopathy as well as liver metastasis.[18] The NCCN recommends CT scans of the chest, pelvis, and abdomen with the use of oral and intravenous (IV) contrast media.[20]
Despite its lack of accuracy (43%-82%) in detecting tumor invasion in the gastric wall, CT scanning has about a 78% sensitivity for detecting enlarged lymph nodes.[20] When this modality is used in conjunction with PET scanning (CT/PET scanning), the results are highly accurate for preoperative staging.[20]
Image A reveals enlarged perigastric lymph nodes on an abdominal CT scan. Image B demonstrates a lesion in the posterior wall of the stomach as well as the presence of enlarged perigastric lymph nodes. Image C is a sagittal view of the abdomen that shows a thickened posterior wall of the stomach, which is suspicious for gastric carcinoma.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Positron emission tomography scanning
Anatomic imaging (eg, CT scanning, magnetic resonance imaging [MRI]) remains the standard diagnostic and staging modality, but functional imaging with PET scanning shows promise, with increasing use across a variety of malignancies.
The role of PET scanning in gastric cancer has been limited, however, because some gastric tumor histologic types have poor uptake of the radioactive tracer (ie, not "PET avid").[8,20,23,24] In addition, PET scanning has a limited ability to distinguish between the primary tumor and perigastric lymph nodes.[24] Nonetheless, this imaging modality is very useful for detecting distant metastatic disease and lymph nodes beyond the perigastric area.[18,23]
The images depict CT/PET scans. The combination of these modalities allows PET-avid activity to be correlated with anatomic features. Images 1b and 2b demonstrate avid lesions in the stomach on PET scans; images 1a and 2a reveal the corresponding anatomic findings on CT scans.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Diagnostic laparoscopy
Diagnostic laparoscopy (staging laparoscopy) has been proposed as a method to identify peritoneal metastatic disease that may not be recognized with standard staging imaging (ie, occult metastases),[8,18,20,25] as well as to reduce the morbidity associated with standard open laparotomy.[25] The minimally invasive direct visualization of the peritoneal cavity allows for tissue biopsy if suspicious lesions are seen. Additional benefits are reduced length of hospitalization following staging alone, faster return to normal activity, and minimal delay for the administration of adjuvant therapy.[26]
Image A shows the laparoscopic setup for gastric surgery. Image B shows peritoneal metastasis (narrow white arrow) detected by staging laparoscopy. The thick white arrow indicates the liver, and the red arrow indicates the stomach.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Treatment
Surgical intervention
Surgical resection offers the only potential of cure for patients with gastric cancer.[8,9,18,20] The main objective of the surgical resection is to achieve negative microscopic margins (ie, an R0 resection); to accomplish this, an en bloc resection with negative proximal, distal, and radial margins is required.[20] The most common procedures performed are a total, subtotal, or distal gastrectomy.
For proximal tumors, a total gastrectomy or subtotal gastrectomy is acceptable,[8,9] with similar overall survival and recurrence rates.[27] However, for middle and distal tumors, controversy exists about the best surgical option.[28] Ultimately, the decision regarding the type of resection used and the extent of nodal dissection should be individualized and made on the basis of the capability to obtain clear margins.[28,29]
If the adjacent organs are involved (eg, the spleen), they should be removed en bloc with the stomach to achieve clear resection margins. Note that the NCCN recommends avoiding routine or prophylactic splenectomy when possible.[20]
The total gastrectomy specimen in the image shows where a gastric tumor was located proximally in the lesser curvature (arrow).
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Minimally invasive approaches
Although conventional open surgery remains the main modality for gastric cancer worldwide, laparoscopic and robotic surgery show great promise.[20,30-33] Experience with these minimally invasive approaches has grown significantly in the last 10 years, aiming to provide oncologic outcomes and survival similar to that achieved with conventional open surgery.
Robotic gastrectomy has proved a feasible approach that seems to improve visualization and facilitates lymph node harvesting with less blood loss in both obese and non-obese patients.[33] Its role in the management of gastric cancer is in its infancy but continues to evolve. The higher cost associated with robotic surgery remains one of the main barriers to its widespread use.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
In general, subtotal gastrectomy has been the preferred approach for middle[28] and distal lesions,[20,28] as long as a complete R0 resection can be achieved. The 5-year survival rates appear to be similar between subtotal and total gastrectomies,[28,29] but functional outcomes may be better with subtotal resection.[28]
Image A shows the plane of transection of the distal stomach. Image B demonstrates the remnant proximal stomach.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Surgical reconstruction
Following a total gastrectomy, reconstruction of the GI tract can be achieved with a Billroth I, Billroth II, or Roux-en-Y procedure.[34] Billroth I reconstructions are not commonly used for gastric adenocarcinoma. Billroth II and Roux-en-Y are the reconstructions most commonly used after gastrectomy for gastric cancer.
The top left image shows the anatomy before a Roux-en-Y reconstruction procedure after a total gastrectomy. The top right image illustrates how the esophagus, duodenum, and small bowel are reconnected following a Roux-en-Y procedure.
The bottom left image shows the areas removed for a gastroduodenostomy (Bilroth I). The bottom right image shows the anatomy after a partial gastrectomy or gastrojejunostomy (Bilroth II).
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
The Roux-en-Y anastomosis is the preferred method of GI tract reconstruction because it avoids the significant postoperative complication of bile reflux that is seen with the Billroth II resection.[34] The Billroth I procedure can be used for small distal tumors. Roux-en-Y anastomosis can be performed with or without creation of a jejunal pouch. Randomized clinical trials have shown better postoperative and long-term quality of life with Roux-en-Y jejunal pouch reconstruction for total gastrectomy.[35,36]
The image shows a Roux-en-Y reconstruction in progress after total gastrectomy. The thick white arrow shows the Roux limb oriented cephalad, toward the gastroesophageal anastomosis; the orientation of the Roux limb indicated by the thin white arrow is caudad, toward the jejunojejunostomy anastomosis.
Image courtesy of Dikken JL, van Sandick JW, Maurits Swellengrebel HA, et al. BMC Cancer. 2011;11:329. [Open access.] PMID: 21810227, PMCID: PMC3175221.[34]
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Lymph node dissection
The role of extended lymphadenectomy in gastric cancer remains controversial,[20,28] and there are marked differences in strategies between clinicians in Western countries (eg, United States, Europe) and those in Eastern countries (eg, Japan, Korea).[34] The letter "D" (dissection) refers to lymphadenectomy on the basis of the anatomic location of the lymph nodes as defined by the Japanese Research Society for Gastric Cancer (JRSC) classification (shown).
D1, or standard, lymphadenectomy requires dissection of the N1 nodal group or nodal stations 1-6.[21] These stations are defined as follows[21,37]:
Stations 1 and 2: Right and left cardial nodes, respectively
Stations 3 and 4: Nodes along the lesser and greater curvatures, respectively (4s = along the short gastric arteries and left gastroepiploic artery; 4d = along the second branch and distal part of the right gastroepiploic artery)
Stations 5 and 6: Suprapyloric and infrapyloric nodes, respectively
D2, or extended, lymphadenectomy includes the N2 nodal group and nodal stations 7-11.[20] These stations are defined as follows[21,37]:
Station 7: Nodes along the left gastric artery
Station 8: Nodes along the common hepatic artery
Station 9: Nodes around the celiac axis
Station 10: Nodes at the splenic hilum
Station 11: Nodes along the splenic artery
Station: 12 = nodes in the hepatoduodenal ligament; 13 = nodes dorsal to the pancreatic head; 14 = nodes at the root of the mesentery; 15 = nodes in the traverse mesocolon; and 16 = para-aortic nodes.[21,37]
Image courtesy of Huang CM, Chen QY, Lin JX, et al. PLoS One. 2014;9(3):e90345. [Open access.] PMID: 24603610, PMCID: PMC3946155.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Two large European trials—the United Kingdom Medical Research Council (MRC) gastric cancer trial and the Dutch D1D2 trial—did not demonstrate an overall survival benefit from a D2 lymphadenectomy over a D1 dissection.[20,38,39] Moreover, the D2 group had higher rates of morbidity and greater blood loss than the D1 group did.[20,38,39]
Analysis of long-term results of the Dutch trial showed D2 dissection was associated with lower loco-regional recurrence and gastric malignancy–related mortality than D1 dissection.[40] However, there were also higher rates of postoperative mortality, morbidity, and reoperation than those seen with D1 dissection. A subgroup analysis found that patients with N2 disease may benefit the most from the extended (D2) dissection.[20,40]
Current NCCN recommendations favor D2 dissection over D1 lymphadenectomy as well as pancreas- and spleen-sparing procedures; operations should be performed by experienced surgeons in high-volume centers to reduce morbidity.[20]
The illustration shows the fascia and vascular anatomy surrounding the splenic hilum, which are taken into consideration when planning laparoscopic spleen-preserving splenic hilar lymphadenectomy in total gastrectomy with D2 dissection. AG = adrenal gland; APF = anterior pancreatic fascia; GSL = gastrosplenic ligament; LN 10 = lymph nodes along the splenic hilum; LN 11 = lymph nodes along the distal splenic vessels; SGVs = short gastric vessels; SRL = splenorenal ligament; and TM = transverse mesocolon.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Chemotherapy
Neoadjuvant chemotherapy has an important role in the management of gastric cancer.[8] It offers the following potential advantages:
The opportunity to assess in vivo tumor sensitivity to a chemotherapeutic regimen
The ability to use the same regimen after surgery
Improving the R0 resection rate
Improving patient tolerability of the chemotherapy before rather than after surgery
The ability to select out patients with more aggressive disease (ie, those whose conditions progress on neoadjuvant therapy)
The UK MRC Adjuvant Infusion Chemotherapy trial (MAGIC) demonstrated that the use of three cycles of perioperative epirubicin, cisplatin, and fluorouracil (ECF) improved progression-free and overall survival for patients with resectable gastric cancer.[41] The 5-year survival was 36% for those who received the chemotherapy and underwent surgery, versus 23% for the surgery-only group.[41]
Other trials have shown similar positive results.[42,43]
Image of a man receiving chemotherapy courtesy of the NCI/Rhoda Baer.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Adjuvant chemoradiation therapy for gastric cancer has also been evaluated. The South West Oncology Group trial 9008 (SWOG-9008) evaluated the use of fluorouracil and leucovorin followed by 4500 cGy after surgery for gastroesophageal cancer and gastric cancer. The study showed an increased overall median survival of 36 months vs 27 months for the surgery alone group (P=0.005). However, increased toxicity was seen in the adjuvant chemotherapy group. The study concluded that adjuvant chemoradiation should be considered in high-risk patients for recurrence of gastric or gastroesophageal cancer.[44]
About 35% of patients with gastric cancer present with distant metastatic disease.[3] Patients with stage IV disease are not candidates for surgical intervention, as the prognosis is very poor in this group.
Medically fit patients with metastatic disease are candidates for palliative chemotherapy with combinations of cisplatin and fluorouracil.[20] Other combination chemotherapy regimens include targeted agents, which may work when standard chemotherapy regimens do not.[8,20] Examples are trastuzumab (which may be used to target HER2-neu) and ramucirumab (recently approved by the US Food and Drug Administration [FDA]), which, in conjunction with paclitaxel, showed a modest increase of 2 months in overall survival in the RAINBOW trial.[45]
Whole body PET/CT scans depicting diffuse metastases courtesy of Wikimedia Commons/Myo Han.
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Radiation Therapy
Perioperative radiation therapy (RT) may also be used for the management of patients with resectable gastric cancer, with or without chemotherapy.[8,20] Preoperative RT may improve regional disease control and patient survival; postoperative RT appears to reduce the rate of recurrence.
In patients with unresectable disease, survival is improved when external beam RT (EBRT) is administered in combination with fluorouracil but not when EBRT is used alone.[20]
Abdul Saied Calvino, MD; N Joseph Espat, MD | April 19, 2018 | Contributor Information
Prognosis
The 5-year survival of patients with gastric cancer varies with the staging at diagnosis. Prognostic factors for poor outcomes include the following[20]:
Positive peritoneal cytology
Advanced disease
Poor performance status
Metastases
Elevated alkaline phosphatase levels (≥100 U/L)
In the United States, the overall 5-year survival for patients with gastric cancer is 30.6%,[3] lower than in some Asian countries such as Japan, because in the US, the majority of these malignancies are diagnosed at a more advanced stage.[3,8-10] In Japan and Korea, where the incidence of gastric cancer is high, national screening programs have increased the rates of diagnosis at early stages and thereby improved survival.[42]
The table shows the observed 5-year survival rates on the basis of staging at diagnosis in US patients with gastric malignancies; these data were collected from the NCI's SEER Program[3] and the American Cancer Society (ACS).[8]
Cervical Cancer: Screening, Recognition, and Treatment
Uterine cervical cancer is relatively rare in the United States but, globally, it ranks fourth among the most common cancers, with the fourth highest mortality rates among cancers in women. Can you differentiate between precursor and cancerous lesions, and do you know the therapeutic options available by stage?Slideshows, September 2015
Gastric cancer is the third most common cause of cancer-related death in the world, and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. In the United States, stomach malignancy is currently the 15th most common cancer.Diseases/Conditions, November 2017
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Authors
Abdul Saied Calvino, MD
Assistant Professor of Surgery
Roger Williams Medical Center / Boston University School of Medicine
Providence, Rhode Island
Disclosure: Abdul Saied Calvino, MD, has disclosed no relevant financial relationships.
N Joseph Espat, MD
Professor of Surgery
Roger Williams Medical Center / Boston University School of Medicine
Providence, Rhode Island
Disclosure: N Joseph Espat, MD, has disclosed no relevant financial relationships.
Editors
Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.
John Heinegg, RN
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: John Heinegg, RN, has disclosed no relevant financial relationships.
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