Gastric cancer

from Wikipedia, the free encyclopedia
Classification according to ICD-10
C16.- Gastric cancer
ICD-10 online (WHO version 2019)
Advanced gastric cancer
An ulcerating gastric carcinoma (see arrow) in a White New Zealander (rabbit).

A gastric carcinoma ( stomach cancer ) is a cancer of the stomach . In contrast to most other types of cancer, the number of new cases per year in western countries has been falling continuously for years. The main risk factors for the development of gastric cancer are a diet rich in nitrosamines and a chronic infection with Helicobacter pylori . Central role in the diagnosis of gastric cancer has the gastroscopy ( gastroscopy ). With the help of small tissue samples that are obtained in the course of such an examination, the diagnosis can be made precisely by the pathologist . In the absence of metastases (daughter tumors), the treatment of choice is surgical removal of the stomach ( gastrectomy ), combined with removal of the local lymph nodes ( lymphadenectomy ). Depending on the tumor stage, in the local tumor stage, chemotherapy may also be carried out before the operation, a so-called neoadjuvant chemotherapy , or after the operation ( adjuvant chemotherapy ). If distant metastases are present, curative therapy is no longer possible. At this stage, if there is evidence of obstruction to the gastric passage, bypass surgery (palliative gastrectomy) is performed. If these symptoms are absent, palliative chemotherapy is carried out depending on the general condition of the patient .

Epidemiology

Stomach cancer is the second most common human tumor worldwide. In Germany , stomach cancer only accounts for around five percent of all malignant diseases. The occurrence varies considerably from region to region. Countries with high occurrences are Japan , Chile , Costa Rica , Colombia , China , Portugal , Russia, and Bulgaria . In these countries the incidence is around four to six times higher than in countries with low risk. In the western world, cancer is now declining compared to other types of cancer. In 1930 it was the most common cause of cancer death in the USA ; today stomach cancer is only responsible for around 2.5% of cancer deaths. This can be explained by better long-term survival of the patients, but is mainly due to the decrease in the incidence rate . This fell from 38: 100,000 in the 1930s to around 5: 100,000 in the 21st century. In most states, men are twice as likely to have the disease as women.

In 2002 just under 20,000 cases were diagnosed in Germany. Since then, over 15,000 new people have contracted gastric cancer every year in Germany, over 9,000 of them men. Men are affected slightly more often than women (ratio around 3: 2). The frequency peak is beyond the age of 50.

Risk factors

Location of the stomach in the digestive tract

Environmental risk factors include Helicobacter pylori infection , diets, and social factors. Chronic infection with Helicobacter pylori, a bacterium that can survive in gastric acid and also promote gastric ulcers , increases the risk of stomach cancer by a factor of five to six. Although not every infection leads to cancer, an infection can be detected in almost all carcinomas of the intestinal type. Iron deficiency increases the risk that a Helicobacter infection will develop into carcinoma.

A diet high in nitrate and nitrite , which can be found in poorly treated drinking water or canned food , also promotes cancer development. Benzo [ a ] pyrene ingested with food can also contribute to degeneration. Also, smoking increases the risk of a previously unknown mechanism of developing gastric cancer. Since these risk factors are mainly present in people with low socio-economic status, stomach cancer occurs more frequently in this population group.

There are also numerous patient-related risk factors that favor gastric cancer. Chronic gastric mucosal inflammation lowers the acid level in the long run and makes the stomach vulnerable to Helicobacter colonization. It also leads to a transformation of the mucous membrane due to the ongoing inflammatory reaction , in which the gastric mucous membrane is replaced by a mucous membrane similar to that of the intestine. These lesions are considered to be the precursors of intestinal-type carcinoma. Patients who have had partial gastric excision also have an increased risk of developing the disease. This is attributed to the flow of basic bile and secretions from the small intestine. Adenomas of the stomach are also to be regarded as precursors of stomach cancer. Carcinoma is found in 40% of the removed adenomas. In addition, around a third of patients with adenoma have cancer elsewhere on the stomach. The ménétrier's disease , in which stomach mucous membrane is generally thickened is as precancerous viewed the stomach.

Genetic risk factors also promote the development of stomach cancer. Patients with blood group A have an increased risk of falling ill. Stomach cancer cases also occur frequently in the context of the autosomal dominant hereditary tumor syndrome HNPCC . Family cases of gastric cancer generally increase the individual risk of developing gastric cancer themselves. There is also a familial gastric cancer syndrome that is based on a mutation of cadherin .

Chronic gastric ulcers rarely become malignant (in up to 3% of cases), but a chronic, non-healing gastric ulcer can also hide an undetected gastric cancer.

A high consumption of fruits and vegetables could protect against lung cancer and cancer of the upper digestive tract (including stomach ). In the EPIC-EURGAST study (2006), men who originally consumed less benefited from an increase to 300 g of fruit and vegetables per day. A connection with other cancer entities has not been proven. The higher the vitamin C level in the blood, the lower the risk of stomach cancer . This was especially true with high meat and sausage consumption.

Symptoms

The diagnosis of gastric cancer is made difficult by the fact that cancers that are still small and could be completely removed surgically do not usually cause any symptoms. Symptoms such as a feeling of fullness in the upper abdomen, which can turn into permanent pain as the patient grows, only appear late. Loss of appetite, often together with nausea and nausea, is a common late symptom, but rarely leads to presentation to the doctor. Swallowing disorders are a symptom of advanced tumors at the entrance to the stomach. Nausea and nausea are more likely to be observed in tumors of the gastric outlet.

Rare symptoms associated with gastric cancer are thrombosis of superficial veins , hemolytic anemia with microangiopathy, and acanthosis nigricans .

Metastases in the ovary , also known as Krukenberg's tumor , are sometimes discovered before the actual stomach tumor .

Diagnosis

Histological preparation of a poorly differentiated adenocarcinoma of the stomach.

During the physical examination of the patient, particular attention should be paid to enlarged lymph nodes above the left collarbone ( Virchow lymph nodes ). Less common locations of lymphogenic metastasis are the region around the navel and the left armpit. Also watch out for signs of ascites , this is a sign of tumor seeding in the peritoneum . In addition, a palpation examination of the liver should be carried out, as this is the most common route of colonization of gastric cancer. An enlargement can give an indication of this.

The most common method of diagnosing gastric cancer is a gastroscopy . As part of this examination, tissue samples are to be taken, since only a histological examination can reliably determine the type and severity of the tumor. To improve on this method, several dyes have been developed that can be applied to the lining of the stomach. The dye methylene blue is absorbed by surface cells of the intestine. Detection of intestinal lining in the stomach or esophagus is an indication of a malignant process or a precursor thereof. The dyes indigo carmine and cresyl violet enhance the contrast of the mucous membrane relief and make irregularities easier to recognize. In addition, zoom endoscopy is now available, in which the mucous membrane can be assessed under 15 to 150 times magnification. Another technique is narrow band imaging. A filter increases the blue component of the light so that irregularities in the mucous membrane can also be seen better.

If the tumor is present, its spread must be determined ( staging ). Endosonography is one means of staging . As with a gastroscopy, an endoscope is inserted into the stomach. The surrounding tissue is assessed from the stomach with the aid of an ultrasound head. Another examination to search for tumor settlements is an ultrasound examination of the abdominal and pelvic area. The computed tomography provides another option for metastases to look, but it does not detect metastases that are less than five millimeters. In 20 to 30% of the CT examinations, the picture is normal, although there are settlements in the peritoneum. Laparoscopy is the most sensitive method for diagnosing these metastases . However, as a surgical procedure, it carries risks for the patient. Complications occur in 3–5%. In around 0.1% of the examinations, the patient dies as a result of the surgery.

Tumor markers have a sensitivity of 9 to 30% in the diagnosis of gastric cancer and are therefore not a useful measure for the detection of the tumor.

Histopathology

The majority of carcinomas show signet ring cells under the microscope . In the cells, the nucleus is marginalized and they react strongly with the PAS staining. More rarely, carcinomas that resemble the glands of the intestine occur. Gelatinous carcinomas have also been described in which there are masses of PAS-positive mucus outside the cancer cells, as well as dedifferentiated carcinomas, the origin of which can only be determined by immunohistochemical methods. In addition to these tumors that originate from the epithelium of the stomach, neuroendocrine tumors have also been described.

Types

There are four types of gastric adenocarcinoma , depending on the type of tumor growth . The polypoid adenocarcinoma grows like a polyp from the inside of the stomach into the stomach lumen . The ulcerating adenocarcinoma is characterized by the formation of damage to the mucous membrane in the form of an ulcer. Compared to benign gastric ulcers, the carcinoma has more irregular margins. Both types each make up a third of gastric cancers. Around a tenth of all gastric carcinomas are of the diffuse type. These tumors do not grow into the lumen, but rather infiltrate the tissue of the stomach. The tumor cells induce fibrosis in the mucous membrane and muscle layers of the stomach, which leads to a thickening of the wall. The diffuse type is associated with a particularly poor prognosis. Early gastric cancer is a tumor that is limited to the mucous membrane or the submucosa . Although around 20% of early cancers have already metastasized at the time of diagnosis, they have a relatively good prognosis compared to the other types.

Much less common than adenocarcinomas are adenosquamous carcinomas, squamous cell carcinomas, and undifferentiated carcinomas.

Molecular biology

Molecular biological findings are becoming more and more important for the assessment of the prognosis and for the choice of therapy. In 2014, based on genetic studies, a classification into four types was proposed:

  • EBV positive tumors
  • MSI tumors
  • genomic - stable tumors
  • Chromosomes - unstable tumors

Genetic and molecular biological analyzes of 295 gastric adenocarcinomas were available from the TGGA (The Cancer Genome Atlas) project. The tissue samples of the tumors were examined with 6 different molecular platforms:

  1. array-based somatic copy number analysis: Procedure for determining the number of somatic DNA copies
  2. whole-exome sequencing: DNA sequencing
  3. array-based DNA methylation profiling: Analysis of DNA hypermethylation
  4. messenger RNA sequencing: sequencing of the mRNA
  5. microRNA (miRNA) sequencing: sequencing of the microRNA
  6. reverse-phase protein array (RPPA): analysis of the proteins formed

Epstein-Barr virus positive tumors

The Epstein-Barr virus could be detected in 9% of the cases. EBV positive tumors often had extremely severe DNA hypermethylation. They often had a PIK3CA mutation and amplified JAK 2, PD-L1 and PD-L2, i. H. these proteins were formed above normal. These tumors would be potential candidates for immunotherapy with PD-L1 inhibitors . So far, however, they have not yet been approved for gastric cancer. Clinical studies have so far been unsuccessful.

MSI tumors

64 tumors showed a very high mutation rate. Microsatellites are formed. The abbreviation MSI stands for "MikroSatellit Instabil". The mismatch repair protein MLH1 is often not expressed, which means that certain DNA damage cannot be successfully repaired. This leads to the development of numerous mutations that could possibly become targets for a target therapy. Hypermethylation of the MLH1 promoter switches off the production of this DNA repair molecule .

Genomically stable tumors

The remaining tumors were identified for the presence or absence of extensive somatic copy-number aberrations (SCNA), i.e. H. the change in gene activity is divided into genomic - stable and chromosomes - unstable. 58 tumors showed a stable genome with few mutations. Histologically, it was often diffusely growing gastric carcinomas. The genes of proteins for cell migration were often activated. Mutations of CDH1 and RHOA were particularly common. A fusion of the CLDN18 and ARHGAP genes was also detected.

Chromosomes - unstable tumors

The remaining 147 tumors belonged to the remaining chromosome unstable group (CIN) with many mutations. Histologically, they were mostly differentiated intestinally. A mutation of TP53, which codes for the protein p53, was particularly common . There was also activation of RTK- RAS .

TNM classification

The TNM classification is used to classify the spread of the tumor (so-called staging). TNM is an abbreviation for

  • T = tumor: extent of the primary tumor
  • N = Nodus: lymph nodes, absence or presence of regional lymph node metastases
  • M = metastases: absence or presence of distant metastases

The 7th edition of the criteria according to the AJCC staging system (American Joint Committee on Cancer) is currently valid .

TNM classification
TX Primary tumor cannot be determined.
T0 No evidence for a primary tumor
Tis Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria
T1 Infiltration of the lamina propria or the tela submucosa (synonym: early carcinoma )
T1a Infiltration of the lamina propria or lamina muscularis mucosae
T1b Infiltration of the tela submucosa
T2 Infiltration of the muscular tunica
T3 Infiltration of the subserous connective tissue without invading the visceral peritoneum or adjacent structures. T3 also includes tumors that spread along the gastrocolic or gastrohepatic ligament and reach the greater or lesser omentum without penetrating the visceral peritoneal surrounding these structures.
T4 Infiltration of neighboring organs ( spleen , transverse colon , liver , diaphragm , pancreas , abdominal wall , adrenal gland , kidney , small intestine or retroperitoneum )
T4a Infiltration of the serosa (visceral peritoneum)
T4b Infiltration of neighboring organs (spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine or retroperitoneum)
NX Involvement of local lymph nodes cannot be assessed
N0 No local lymph nodes involved
N1 Metastases in one or two local lymph nodes
N2 Metastases in three to six local lymph nodes
N3 Metastases in seven or more local lymph nodes
M0 No distant metastases detected
M1 Distant metastases

therapy

Overview of gastric cancer therapy
(details in the text)
TNM stage therapy
uT1aN0M0 *
(mucosal carcinoma, early gastric carcinoma)		 Endoscopic resection (EMR, ESD)
all stages ≥ uT1b * (operable) Surgery (complete or partial gastrectomy
with D2 lymphadenectomy)
Stages uT3 and uT4 * (operable) in addition to the above-mentioned operation:
neoadjuvant chemotherapy with cisplatin
and fluorouracil (or oxaliplatin, capecitabine);
The importance of adjuvant (radio) chemotherapy
is controversial and has not yet been recommended
locally inoperable or metastatic (M1) Palliative chemotherapy based on the above substances,
if possible with HER2 positivity with trastuzumab
* The letter 'u' in the formula represents TNM by U ltraschall, d. H. Findings obtained by endosonography

The most important treatment measure is the surgical removal of the tumor, as completely as possible, with a safety margin of 5 cm for the intestinal type and 8 cm for the diffuse type. Depending on the location, this results in a partial (4/5) or complete removal of the stomach , possibly including parts of the esophagus or the duodenum . A 4/5 resection according to Billroth is only possible in the intestinal type in connection with a localization in the lowest part of the stomach, the antrum. In all other cases, a gastrectomy with a Y-Roux disconnected jejunal loop must be performed if there is a prospect of healing. The surrounding lymph nodes are also removed, and if infiltrated, the spleen or parts of the liver are also removed . Then the remaining end of the stomach or esophagus is reattached to the duodenum (surgical technique according to Billroth  I or II).

Local ablation or endoscopic resection

If gastric carcinoma is limited to the mucous membrane ("mucosal carcinoma" stage T1aN0M0, this can be determined with a high degree of certainty by an endoscopic examination), the therapy consists of a local endoscopic ablation. Two different techniques are used here: endoscopic mucosal resection (EMR), in which the lesion is first injected with sterile saline and then removed with a sling, or endoscopic submucosal dissection (ESD), in which the lesion is removed microsurgically. The latter has the advantage that the lesion can be removed en bloc, which facilitates the later histopathological assessment. However, ESD is also associated with slightly higher complication rates.

Neoadjuvant chemotherapy

In the operable stages T1b, T2, T3, T4, endoscopic ablation is no longer possible or useful. Instead, an operation (complete or partial gastrectomy ) with so-called lymph node dissection (removal of the draining lymphatic pathways with lymph stations) should be carried out.

In the case of operable gastric carcinomas of stage T3 or T4, the German guidelines generally recommend performing neoadjuvant chemotherapy, i.e. H. chemotherapy before the operation to reduce the size of the tumor and thus improve the outcome of the operation. Two large therapeutic studies have shown a survival advantage for patients treated in this way compared to untreated chemotherapeutically, on the one hand the British MAGIC study, in which patients were treated with a combination of epirubicin, cisplatin and fluorouracil ("ECF"), and on the other hand the French FNCLCC / FFCD study in which patients received cisplatin and fluorouracil. Instead of fluorouracil and cisplatin, capecitabine and oxaliplatin are often taken today because they are better tolerated . Another very promising combination is docetaxel - oxaliplatin - fluorouracil.

Adjuvant chemotherapy or chemoradiotherapy

The importance of adjuvant chemotherapy or chemoradiotherapy (i.e. chemotherapy possibly combined with radiation therapy after the operation) is currently assessed differently. According to German guidelines (as of December 15, 2012), adjuvant therapy is generally not recommended. The only exception is the situation when the tumor could not be completely removed surgically. In Asian countries this is assessed and handled differently and adjuvant therapy is often carried out, e.g. B. with capecitabine and oxaliplatin.

Palliative therapy

If the tumor is primarily inoperable (e.g. because it is close to large blood vessels, “locally advanced carcinoma”) or shows multiple distant metastases, healing is usually no longer possible. Therapy then no longer takes place with curative (“healing”), but with palliative (“relieving”) objectives. With the chemotherapeutic agents mentioned above, symptoms can be alleviated and the survival time extended in most cases. If the tumor is histopathologically HER2- positive, trastuzumab (Herceptin®) should be used if possible .

rehabilitation

After a complete or partial removal of the stomach, the patient can experience various disorders which require their own measures to increase the patient's quality of life after the operation. Removal of all or part of the stomach leads to faster passage of food into the small intestine. This can lead to a dumping syndrome , which in the patient can lead to osmotic swelling of the small intestine and vasomotor disorders with a drop in blood pressure up to syncope immediately after eating. This is known as early dumping. The other side of the disease, so-called late dumping, is based on the fact that easily digestible carbohydrate-rich food is absorbed too quickly. This leads to excessively high blood sugar , which the body tries to control by releasing excessive amounts of insulin . However, since too much insulin is usually released, hypoglycaemia occurs a few hours after eating , which is very stressful for the patient. Dumping syndrome can be relieved by dietary measures such as eating smaller but more frequent meals, avoiding fluid intake with food, or lying down after meals.

Reflux esophagitis can develop after partial gastric removal if proximal parts of the stomach have been removed. Basic duodenal secretion can also get into the stomach or the esophagus and cause pain, nausea or chronic inflammation there. These problems can be remedied by raising the head end of the bed or by medication. Fat digestion can also cause problems for the patient, as the food can no longer be stored in the stomach, which reduces the time the pancreas has to secrete fat-digesting enzymes . As a therapy, the fat content of the food can be reduced; the enzymes can also be supplied exogenously. Many patients experience malassimilation syndromes in which food components cannot be digested or absorbed to a sufficient extent. Therefore, the patient should be advised of a sufficient intake of calories and vitamins and minerals and trained accordingly. Likewise, almost all patients with a complete stomach removal develop a deficiency in vitamin B12 . This causes anemia with a latency of three to five years . As a result, vitamin substitution is indicated in every patient. Bone metabolism disorders also occur in patients after the operation, which strongly promote osteoporosis . On the one hand, this is attributed to reduced calcium intake , since most patients can no longer tolerate dairy products after the operation. On the other hand, there is often a vitamin D deficiency . Calcium and vitamin D can be supplied exogenously. In addition, the cancer and the surgical procedure usually represent a strong psychological burden for the patient. The patient's ability to cope with his illness should therefore be supported by psychological care if necessary.

Aftercare

So far, it has not been possible to show that follow-up examinations lead to an early detection of recurrences and thus to better survival. Therefore, the recommendations for specific aftercare in the current guidelines are cautious. No routine diagnostic tests such as B. gastroscopy, sonography, chest X-ray or even computer tomography are recommended. It is of course a different matter if the patient being followed up has specific complaints that could be caused by a relapse. Corresponding diagnostics must of course be carried out here, although the prognosis of patients with a symptomatic (= discomfort-causing) relapse is generally poor.

prevention

Since the nutritional profile covers many risk factors, and on the other hand the protective effect of fruit and vegetables is known, unhealthy eating habits should be fundamentally changed. Above all, frequent consumption of meat and cured foods should be reduced. Smoking cessation is fundamentally beneficial to health.

If Helicobacter pylori infestation is proven , its eradication (drug removal) should be sought. If stomach cancer is common in the family or if there is chronic gastritis, regular gastroscopy is recommended.

The German Cancer Research Center assumes that the registered decrease (between 1977 and 1997 by around a quarter) in gastric cancer is due to the massive spread of refrigerators and the year-round provision of fresh fruit and vegetables and a related decrease in preservation by means of curing and smoking is due.

The earlier the stomach tumor is detected, the more successfully it can be treated.

forecast

Since stomach cancer is usually only diagnosed at a very advanced stage (70% of all cases are detected in tumor stages III and IV), the overall death rate is relatively high. With early detection (stage I), the 5-year survival rate is 65 to 80%, with advanced cancer stages it drops dramatically. For Western Europe, the 5-year survival rates according to collective statistics are 65% in stage I, 22% in stage II and 5% in stage III. A 5-year survival time is not to be expected in tumor stage IV. If you survive the first five years, there is a 50 to 90 percent chance of permanent cure.

literature

Web links

Wiktionary: gastric cancer  - explanations of meanings, word origins, synonyms, translations
Wiktionary: stomach cancer  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ a b c d e Chen Liu, James Crawford: The Gastrointestinal Tract. In: Vinag Kumar, Abul Abbas, Nelson Fausto (Eds.): Pathologic Basis of Disease. 7th edition. Philadelphia 2005, pp. 823-826.
  2. ↑ C. Thomas: Histopathology. Stuttgart, 2006, p. 139.
  3. ↑ German Cancer Aid , current statistics 2013.
  4. ↑ JM Noto, JA Gaddy u. a .: Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans. In: The Journal of clinical investigation. Volume 123, Number 1, January 2013, pp. 479-492, ISSN  1558-8238 . doi: 10.1172 / JCI64373 . PMID 23257361 . PMC 3533289 (free full text).
  5. ^ A b c Robert Mayer: Gastrointestinal Tract Cancer. In: Anthony Fauci u. a. (Ed.): Harrison's Principles of Internal Medicine. Volume 1, New York 2008, pp. 571-573.
  6. ^ Frank Mitros, Emanuel Rubin: The Gastrointestinal Tract. In: Raphael Rubin, David Strayer u. a. (Ed.): Rubin's Pathology. 5th edition. Philadelphia 2008, p. 569.
  7. ↑ Adapted from: What protects against cancer and diabetes? In: MMW update. Med. No. 24/2007 (149th year), p. 16, there cited from EPIC Symposium , Berlin, April 25, 2007.
  8. ↑ a b c d Ch. Englisch-Fritz u. a .: Diagnosis of gastric cancer. In: The oncologist. 14, 2008, pp. 332-338.
  9. ↑ C. Thomas: Histopathology. Stuttgart 2006, p. 139.
  10. ^ Frank Mitros, Emanuel Rubin: The Gastrointestinal Tract. In: Raphael Rubin, David Strayer u. a. (Ed.): Rubin's Pathology. 5th edition. Philadelphia 2008, p. 571.
  11. ^ The Cancer Genome Atlas Research Group: Comprehensive molecular characterization of gastric adenocarcinoma. In: Nature 2014; Volume 513: pp. 202-209 doi: 10.1038 / nature13480
  12. ↑ Julia Borsch: Avelumab does not reach the endpoint. In: deutsche-apotheker-zeitung.de. November 29, 2017. Retrieved June 26, 2019 .
  13. ↑ K. Washington: 7th edition of the AJCC cancer staging manual: stomach. In: Ann Surg Oncol . 17, 2010, pp. 3077-3079.
  14. ↑ a b c d G. Woeste, Salah-Eddin Al-Batran , J. Albert, J. Trojan: Diagnosis and therapy of gastric carcinoma. In: Oncologist. 2014; 20, pp. 1139-1152. doi: 10.1007 / s00761-014-2792-1
  15. ↑ D. Cunningham, WH Allum, SP Stenning, JN Thompson, CJ Van de Velde, M. Nicolson, JH Scarffe, FJ Lofts, SJ Falk, TJ Iveson, DB Smith, RE Langley, M. Verma, S. Weeden, YJ Chua, MAGIC Trial Participants: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. In: N Engl J Med. 2006; 355 (1), pp. 11-20. PMID 16822992 . doi: 10.1056 / NEJMoa055531
  16. ↑ M. Ychou, V. Boige, JP Pignon, T. Conroy, O. Bouché, G. Lebreton, M. Ducourtieux, L. Bedenne, JM Fabre, B. Saint-Aubert, J. Genève, P. Lasser, P. Rougier: Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. In: J Clin Oncol. 2011; 29 (13), pp. 1715-1721. PMID 21444866 . doi: 10.1200 / JCO.2010.33.0597
  17. ↑ a b Gastric carcinoma - diagnosis and treatment of adenocarcinomas of the stomach and esophagogastric junction. AWMF online, accessed on December 8, 2014 (version of the guideline: December 15, 2012, valid until December 31, 2015 at the time of access).
  18. ↑ YJ Bang, E. Van-Cutsem, A. Feyereislova, HC Chung, L. Shen, A. Sawaki, F. Lordick, A. Ohtsu, Y. Omuro, T. Satoh, G. Aprile, E. Kulikov, J. Hill, M. Lehle, J. Rüschoff, YK Kang; ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. In: Lancet. 2010; 376 (9742), pp. 687-697. PMID 20728210 . doi: 10.1016 / S0140-6736 (10) 61121-X .
  19. ↑ a b c H. Delbrück, H. Wilke: Rehabilitation of patients with gastric carcinomas. In: The oncologist. 6, 2000, pp. 6-13.
  20. ↑ Guideline for gastric carcinoma ( Memento from July 13, 2015 in the Internet Archive ) (PDF)