Gastric Carcinoma

Introduction

In contrast to Asian countries, in Western Europe the incidence of gastric cancer is declining. Still, at number 5 for men and 6 for women it is among the most common forms of cancer. Moreover, largely due to its still poor overall prognosis (5-year-survival rate of 20% to 30%) it remains one of the most common causes of death from malignancy. Treatment strategies today are based a multimodality concept in which visceral surgery plays the major role. In Japan the incidence of gastric cancer is 5 times higher than in the West. In response, Japan has developed very good screening programs that reliably detect early forms of gastric cancer and have led to a clearly higher incidence of early gastric cancers. Such a screening program would not be practicable in Germany due to the much lower incidence of gastric cancer; it is also not recommended in the S3 guidelines.

Localization

Gastric carcinomas are classified according to whether they are located in the distal third, the middle third, or the proximal third of the stomach. The latter are currently increasing in incidence, but the most frequent localization is the distal third (Antrumbereich).
Adenocarcinomas of the esophagogastric junction (AEG) are divided in the AEG classification into adenocarcinomas of the distal esophagus (AEG type I), true carcinomas of the cardia (AEG type II) and subcardial carcinomas (AEG type III). The classification plays a key role in the choice of surgical procedure on the extent of the resection. AEG III tumors require a gastrectomy, AEG II tumors a transhiatal extended gastrectomy, and AEG I tumors esophageal resection.

Macroscopy

Based on macroscopic appearance, gastric carcinomas are divided according to the Borrmann classification into 4 types, which play however a rather subordinate clinical role.

Histology

More important is the their histological classification. The WHO classification distinguishes 8 different types, of which adenocarcinomas comprise the overwhelming proportion. The classification of Laurén was introduced in 19651. It makes a distinction according to the main histological types of gastric carcinoma, namely intestinal and diffuse.

Differentiation

Finally, gastric carcinomas can be classified into 4 types according to their differentiation, G1=well differentiated, G2=moderately differentiated, G3=poorly differentiated, and G4=undifferentiated.

Intestinaler Typ

Intestinal Type

Diffuser Typ

Diffuse Type

Intestinal Type

The intestinal type of gastric carcinoma is generally macroscopically well defined, tends to grow continuously, and has a gland-like differentiated appearance under the microscope that resembles intestinal mucosa. Because this type occurs preferentially in certain age groups and regions, it is also called the epidemic type of gastric carcinoma.

Diffuse Type

Because this type is influenced more by genetic factors than by lifestyle it is also known as an endemic type. It is macroscopically harder to demarcate and shows a diffuse histological growth pattern with widely disseminated tumor cells. Because of the diffuse spread, it is difficult to reliably distinguish the tumor margins macroscopically, making it imperative to maintain a wider safe resection margin.

Etiology

Risk factors for gastric carcinoma include chronic infection with Helicobacter pylori, chronic atrophic gastritis, type A, high dietary nitrite intake (with gastric acid-catalyzed formation of nitrosamine), gastric ulcer, and prior gastric surgery (gastric stump carcinoma status following Billroth II resection). The suspicion that certain dietary habits increase the risk of gastric cancer is supported by the observation of Japanese emigrants to Western countries. If they adopt Western dietary habits, their risk of gastric carcinoma drops dramatically, if they retain their customary diet in their new homes, the incidence remains high.

A rare precancerous condition is Ménétrier disease, or hypoproteinemic hypertrophic gastropathy, which is often accompanied by H. pylori infection and which progresses to gastric carcinoma in 10% of patients.

Helicobacter pylori

Helicobacter pylori

Symptoms

The complete lack of early symptoms makes timely recognition of gastric carcinoma enormously difficult. Early symptoms are the exception and usually constitute incidental findings. Unspecific epigastric pain should therefore always be differential diagnostically clarified by endoscopy, which is highly sensitive for gastric carcinoma. Patients with one or more of the following alarm symptoms clinically associated with suspected esophageal or gastric carcinoma should be referred to early endoscopy with extraction of biopsies:

  • Dysphagia
  • Recurrent vomiting
  • Inappetence
  • Weight loss
  • Gastrointestinal bleeding

AEG Classification

Adenocarcinomas of the esophagogastric junction (AEG) are divided in the AEG classification into adenocarcinomas of the distal esophagus (AEG type I), true carcinomas of the cardia (AEG type II) and subcardial carcinomas (AEG type III). The classification plays a key role in the choice of surgical procedure on the extent of resection. AEG III tumors require a gastrectomy, AEG II tumors a transhiatal extended gastrectomy, and AEG I tumors esophageal resection.

aeg-klassifikation

Diagnostik

Exophytisch wachsender Tumor

exophytic tumor growth

Szirrhöser Tumor

szirrotic tumor

Endoscopy

The examination method of choice is endoscopy. It allows macroscopic and histological diagnosis as well as reliable tumor localization. Supplemental endoscopic ultrasound can be used for local assessment of the extent of spread. More difficult to evaluate by endoscopic ultrasound is the regional lymph node metastatic spread.

by courtesy of Albertinen-Krankenhaus in Hamburg

Sonography

Perkutaneous sonography of the neck in gastric cancer can be performed to rule out lymphatic metastasis. In AEG-II-tumors it should be undertaken regularly in addition to other staging examinations. At the junction of the thoracic duct in the left subclavian vein, a lymphnode metastasis can be present. It is then called "Virchow-Lymphnode"

sonografie der Schilddrüse

CT Abdomen mit Magen-CA

CT-scan in gastric cancer

PET-CT bei Magen-CA

PET-CT in gastric cancer

Staging

The extent of gastric carcinoma spread is evaluated by endoscopy with tissue removal for biopsy, and CT (Schnittbildgebung) of the thorax and abdomen. CT can confirm or exclude distant metastases. Endosonography can assess depth the tumor penetration in the gastric wall layers.

It can also detect possible lymph node metastases. In individual cases, PET scan can help to clarify suspicious masses, e.g. whether a metastasis is present in the liver.

Staging Laparoscopy

Gastric carcinoma metastasis occurs along hematogenous and lymphogenous pathways as well as per continuitatem in the form of peritoneal carcinomatosis. This is difficult to recognize in CT images, especially if they are present in limited extent. The presence of a peritoneal carcinomatosis, however, is of major importance for therapy since curative resection is then usually no longer possible and the patient can be spared a laparotomy.

Palliative resection should not be performed for gastric carcinoma unless rendered necessary by an obstruction refractive to treatment or by bleeding. Staging laparoscopy can exclude a peritoneal carcinomatosis before gastrectomy. It can also disclose previously overlooked liver metastases and obtain peritoneal wash cytology (PWC) specimens.

The finding of malignant cells in PWC correlates with a poor prognosis, but does not change treatment. If a peritoneal carcinomatosis is present in gastric carcinoma then, depending on the circumstances, intraoperative hyperthermal intraabdominal chemoperfusion (HIPEC) can be performed. For this situation, several studies have described the use of a neoadjuvant approach with intraperitoneal chemotherapy.

laparoskopie

during laparoscopy

s3

No evidence supports the use of tumor markers. Numerous studies have investigated the importance of markers ranging from known markers like carcino-embryonic antigen (CEA), carbohydrate antigen (Ca)19–9 and Ca72–4, to novel markers that may also provide clues of tumor metabolism or pathophysiological changes in the stomach related to carcinogenesis (pepsinogen). For none of these markers are the reported sensitivity and specificity adequate for primary diagnosis, which renders them unsuited as tools for screening or staging. The barium meal test is also not appropriate for staging of tumors of the stomach or esophagogastric junction. The localization of the tumor can be determined by endoscopy and CT reconstruction techniques.

Interested in current diagnostic and treatment standards in Germany for gastric carcinoma? Then read the evidence-based
S3-guidelines on diagnosis and treatment of gastric carcinoma.

Therapy

The decisive factor in treatment of gastric carcinoma that most dramatically impacts overall prognosis is surgery. The goal here is always to achieve an R0 resection, i.e. a resection macroscopically and microscopically im Gesunden leaving no residual tumor in the body.

The gastrectomy is supplemented by removal of all lymph nodes directly surrounding the stomach (D1 segment) and along the truncus coeliacus, the hepatic artery, and the splenic artery (A. lienalis) (D2 segment). In Japan it is standard to perform an extended lymphadenectomy encompassing the D3 (DIII) segment.

This practice is based on the fact that Asian patients have less visceral fat, which also makes this step technically more simple. Metastases in the paraaortal and mesenteric  lymph nodes (D3 segment) are judged to be distant metastases, their resection offers no advantage with regard to overall survival but does increase the procedure’s morbidity.

CT Abdomen mit Magen-CA

initial CT-scan

Magenca neoajduvante Behandlung

after neoadjuvant chemotherapy

Risk Evaluation

The preconditions for successful surgery are resectability of the tumor and operability of the patient, i.e. the functional operability. Patients with gastric carcinoma are often under- or malnourished, which can have a major impact on postoperative outcome and development of e.g. anastomotic insufficiency. The patient’s overall physical capacity and comorbidities must also be taken into account.

Multimodality Therapy Concepts

In locally advanced tumors (uT3/uT4) neoadjuvant chemotherapy can be used to achieve tumor downsizing and downstaging and thus increase the chances of an R0 resection. After conclusion of prior chemotherapy, a re-staging examination is usually performed to assess the tumor’s response to treatment. Even if the response is good, subsequent resection is obligatory since the rare case of a complete response can only be established on a histologic specimen by a pathologist.

Surgical Resection

The location of the tumor and its histological type according to the Laurén classification affect the choice of surgical procedure. AEG-II tumors of the cardia are treated by extended transhiatal surgery in which the complete stomach and the distal part of the esophagus are resected. In gastric carcinoma it is standard to perform a gastrectomy.

Only in intestinal tumors located very far distally can subtotal or 4/5 gastric resection be carried out, provided care is taken to provide an adequate safe resection margin. This does not affect overall survival , but the quality of life after subtotal gastric resection is clearly better.2

An obligatory component of every gastrectomy for gastric carcinoma is omentectomy, i.e. removal of the membranous double layer of fatty tissue that has its evolutionary origin in the stomach. A bursectomy is also carried out, i.e. resection of the bursa omentalis on the pancreatic surface.

Transhiatal erweiterte Gastrektomie bei AEG II-Tumor

Transhiatal extended total gastrectomy

Gastrektomie mit Omentektomie, Bursektomie und DII-Lymphadenektomie

Total Gastrectomy

Subtotale Gastrektomie bei distal lokalisierten intestinalen Tumoren

Subtotal gastrectomy

Lymphadenectomy

A systematic DII lymphadenectomy encompasses the removal of all perigastric lymph nodes and the nodes surrounding the celiac trunk, the hepatic artery, and the splenic artery. Usually more than 25 lymph nodes are removed and examined histologically. To achieve “pN0” in subsequent tumor staging, at least 16 regional lymph nodes should be examined and classified as tumor free. The spleen is not as a rule resected.3

Reconstruction

Restoration of intestinal continuity is done by pull-up of a small bowl loop. Patients experience improved swallowing function and quality of life if the small bowel loop is doubled to create a so-called pouch. A pouch however cannot be created intrathoracally, so this option is not available for AEG-II tumors.

If the patient is not functionally operable, definitive radiochemotherapy with curative intent can be administered. Otherwise perioperative chemotherapy, i.e. applied before and after surgery, is the standard procedure for advanced tumors. Preoperative radiochemotherapy is not indicated for gastric carcinoma.

DII-Lymhpadenektomie

Early Gastric Carcinoma

Early gastric carcinoma invades only the mucosa and submucosa. The Japanese classification differentiates between slightly raised (erhabenen), flat, and depressed types. Because of the excellent lymphatic drainage (Versorgung) of the submucosa, progression of the infiltration from the mucosa to the submucosa increases the probability of lymph node metastases from 4% or 5% to 22%. Early gastric carcinoma can be treated by endoscopic resection if the following criteria are met:

  • Lesions <2 cm in slightly raised  type
  • Lesions <1cm in flat type
  • No macroscopic ulceration
  • Histological differentiation stage well or moderate (G1/G2)
  • Invasion limited to the mucosa

Resection should be performed in a center with ample experience with the procedure. The resection should be en-bloc, which also allows for complete histological evaluation of the tumor margins.

Ösophagusverätzung

Ulkuskrankheit