Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
67 Cards in this Set
- Front
- Back
|
two main histologic variants
|
intestinal type
diffuse type |
|
|
PRECURSOR LESIONS FOR INTESTINAL TYPE CANCERS
|
Atrophic gastritis
Intestinal metaplasia Dysplasia |
|
|
One model for the "intestinal type" of gastric cancer describes a progression from chronic gastritis to chronic atrophic gastritis, to
|
intestinal metaplasia, dysplasia, and eventually to adenocarcinoma
|
|
|
Longstanding chronic superficial gastritis caused by _______leads eventually to_________
|
- chronic H. pylori infection, pernicious anemia, or possibly a high salt diet
- chronic atrophic gastritis and intestinal metaplasia |
|
|
Atrophic gastritis
|
progressive atrophy of the glandular epithelium with loss of parietal and chief cells
- hypochlorhydria (decrease in hydrochloric acid) and a resultant increase in gastric pH - high pH in the stomach permits microbial colonization, some of which possess nitrate reductase, allowing nitrosation that is genotoxic - increased 5.7-fold - |
|
|
Intestinal metaplasia
|
- potentially reversible change from one fully differentiated cell type to another
- The most common form of metaplasia in the stomach is the intestinal type - result of Helicobacter pylori infection, bile reflux, or can be induced experimentally by irradiation |
|
|
Dysplasia
|
- In gastrectomy specimens for gastric cancer, 20 to 40 percent of patients have associated dysplasia
- |
|
|
PRECURSOR LESIONS FOR DIFFUSE TYPE CANCERS
|
NO clearly defined precancerous lesion
|
|
|
ENVIRONMENTAL RISK FACTORS
|
Diet
Smoking Alcohol Socioeconomic status Reproductive hormones Epstein-Barr virus Helicobacter pylori |
|
|
Diet
|
Nitroso compounds
Salt Folate |
|
|
Smoking
|
increased by approximately 1.5 to 1.60-fold
|
|
|
Alcohol
|
- not been demonstrated
- daily intake of wine may be protective |
|
|
Helicobacter pylori
|
6-fold increase in the risk with adenocarcinomas distal to the cardia
|
|
|
HOST-RELATED FACTORS
|
Blood group
Familial predisposition Hereditary diffuse gastric cancer Genetic polymorphisms Gastric polyps Hypertrophic gastropathy and immunodeficiency syndromes Gastric ulcer Pernicious anemia |
|
|
Diagnostik
o |
o Gastroskopie
• Indikation Dyspphagie Innappetenz Gewichtabnachme Blutung Rezidiv Erbrechen • Endosono T • Diagn geuigkeit • 60-90% • T Stadium N • Keine specifitat Fernmetastasen • Nicht specifisch Aszites • Hohere Spezifitat Leber • Die Abschnite in der nahe • Punktion Mediast LK |
|
|
Staging o
|
• Intraepitheliale Neoplasie
Low grade High grade • Von externen Pathologe noch mal untersuchen lassen • Ultraschall • CT THORAX • CT ABDOMEN • Nicht unbedingt Knochen Szintigraphie PET CT Breischluchuckuntersuchung • Zur Hohelokal nicht empfohlen • Besser gastroskopie Computertomographie • Laparoskopie cT3-4 Zytologie • Progn Faktor • Andert Therapi nicht o Makroskopisch V.a. Karzinom linitis Plastika • Kurzfristig Untersuchung • Endoskopische Resektion o Labor • Tu Marker nicht empfohlen o Nach neodejuv Therapie • Ct oder endoskopie • Restaging nicht erforderlich • Metastasenausschluss soll gemacht w |
|
|
Screening o
|
o Keine serologische Untersuchung empfohlen
o Fokale atrophie Intersinale metaplasie • Mussen nicht endoskopisch untersucht werden o Gastroskopie profil nicht empfohlen • Nach Operation auch nicht empfohlen o NSAR Aspirin • Sollen nicht prof angew w • Risiko o Helicobakter pylori • Cag a 2.5 risk • Immer chronische Gastritis • Eridikation empfohlen o Alter • Uber 55 o Alkohol o Nikotin o Pernitiose Anaemie o Familien Faktoren • Verwandte est grad 2-3 fach • Diffus ca • Fruhes erkrankungsalter • Soll genetische Beratung erfolgen CDH 1 • Prof Gastrektomie • Triten Lebensdekade • 5 Jahre vor Erkrankungalter • Halb Jahr ein Jahr Gastroskopie • Ab 16 Jahre alt • HNPCC Gastroskopie • Bis zum Tretz band o Magenoperationen o Ubergewicht o Reflux Krankheit o PPI • Erhohten Risk Nicht bewiesen |
|
|
Brief o
|
o Verlauf
• Dietische beratung o Empfehlung • Regelmasige Ernahrungsberatungen Zu empfehlen sind regelmäßige ernährungsmedizinische Verlaufskontrollen ggf. mit Wiederholung der Ernährungsberatung. • Supplemente mit Omega-3-Fettsäuren Aufnahme von 1,5 g/Tag empfohlen • Kontrolle Schmerz, Übelkeit, Obstipation, Depression und Mundhygiene o Medikamente • Supplemente mit Omega-3-Fettsäuren Aufnahme von 1,5 g/Tag empfohlen |
|
|
Ernahrung o
|
• Reduz EZ
Schlechter Lebensqualitat Mehr komplikationen Geringer Ansprechen der Therapie Geringer Aktivitat Soll immer beurteilt werden Schlechtere Prognose • Nutritional Risk Score • Patienten vor großen Tumorresektionen im oberen GI-Bereich sollten auch ohne Zeichen einer Mangelernährung präoperativ immun-modulierende Trinklösungen einnehmen, die Arginin, Omega-3-Fettsäuren und Ribonukleotide enthalten. Medikament? • Enteraler Nahrungzufuhr Vorzug • Eine über 5-7 Tage präoperativ verabreichte immun-modulierende Trinklösung mit Arginin, Omega-3-Fettsäuren und Ribonukleotiden mit post-operativ enteraler Fortsetzung der Ernährungstherapie Ohne Mangelernahrung • - perioperativ voraussichtlich für mehr als 7 Tage keine Nahrung zu sich nehmen konnen - perioperativ voraussichtlich über mehr als 10 Tage oral nur unzureichend (<60% der empfohlenen Zufuhr) ernähren werden Mit Mangelernahrung • sollten für eine Dauer von 10-14 Tagen präoperativ eine gezielte Ernährungstherapie erhalten, auch wenn dafür die Operation verschoben werden muss. • Nach op Nach Ösophagektomie oder Gastrektomie sollte eine enterale Sondenernährung frühzeitig innerhalb von 24 Stunden postoperativ begonnen werden. • distal der Anastomose • Sondenernährung sollte mit geringer Flussrate (10-20 ml/h) begonnen • Risiko intestinalen Ischämie Esophagektomie • Stenose • Feinnadel-Katheterjejunostomie (FKJ) sollte gerade nach Ösophagusresektion für mindestens 6 Wochen belassen Supplemente mit Omega-3-Fettsäuren • Aufnahme von 1,5 g/Tag empfohlen • EZ - Gewichtsverlust >10-15% innerhalb von 6 Monaten - BMI <18.5kg/m² - Subjective Global Assessment (SGA) Score C - Serumalbumin <30g/l (ohne Zeichen einer Leber- oder Nierenstörung) • Sonden zur Ernahrung PEG nicht moglich nach Gastrektomie PEJ-Sonden (endoskopisch angelegte perkutane Jejunostomie) und Feinnadel-Katheterjejunostomien (FKJ). • Ernährung in Sterbephase minimale Mengen an Essen und wenig Wasser um Durst und Hunger zu stillen |
|
|
Endoskopische Therapie o
|
• Resektion ausreichend
Oberflächliche Magenkarzinome, die auf die Mukosa begrenzt sind (T1a N0 M0), können unter Berücksichtigung folgender Kriterien mit einer endoskopischen Resektion behandelt werden (basierend auf der Japanischen Klassifikation der Magenkarzinome): • Läsionen von < 2 cm Größe in erhabenen Typen • Läsionen von < 1 cm Größe in flachen Typen • Histologischer Differenzierungsgrad: gut oder mäßig (G1/G2) • Keine makroskopische Ulzeration • Invasion begrenzt auf die Mukosa • Keine restliche invasive Erkrankung nach ER • Soll en block gemacht w • Nur von erfahrenem Endoskopist • Lokale Rezidive 10% Konnen wieder endoskopisch behandelt werden • R1 Zweiten Versuch • R1 • Operation • Nur 50% tumor • R0 • Beobachtung • Komlikationen Blutung Perforation • Nachsorge 3 monate erste Jahr 6 monate zweite Jahr Danach Jahrlich |
|
|
Chirurgische o
|
• Resektion
Abstand • Diffus • 8 cm • Intestinal • 5 cm • Sieverrt III II • Erweiterte Gastrektomie Principen • Alles en block • Keine Splenektomie • Laparoskopisch noch nicht empfohlen • Keine rad Operation • T4b • Metastasen • Dissektion • LK I II • Mehr als 25 LK • Mindestens 16 LK fur N0 • Palliative op • Nicht bei asympt Tumoren • Peritonektomie • Nicht empfohlen • R1 • Operation • Op nicht moglich • Radiochemotherapie • Inoperabel • Radiochemotherapie |
|
|
Postoperativ o
|
Bei neodjuv Therapie
• Adjuv Chemotherapie Metastasenachweis • Keine Chemotherapie weiter R0 Resektion • Keine Chemotherapie • <D2 lymphadenektomie • Kann chemotherapie durchgefurt w |
|
|
Multimodale Therapie o
|
• uT2
Neo chemo und aduv Therapie • Cisplatin • 5-FU • uT3 uT4a Neo chemo und aduv Therapie • Cisplatin • 5-FU • Gastroesoph ubergang Chemotherapie Neoadjuvante Radiochemotherapie • Praop radiochemo Soll nicht durchg w • Preop antikorper Soll nicht • Neodjuvante Therapie Progress • Beurteilung • Symptomorient Diagnostik • Fruhzeitige Operation |
|
|
Palliative Therapie o
|
• Guter AZ
Chemotherapie • Soll wie schnell wie moglich begonn Eine palliative medikamentöse Tumortherapie sollte zum frühest möglichen Zeitpunkt nach Diagnosestellung der lokal fortgeschritten inoperablen oder metastasierten Erkrankung eingeleitet werden • Dauer • Abhangig von az Tumoransprechend • HER2 status • Prediktiv fur Therapie mit Trastuzumab • Uberexpression Aufgrund eines nachgewiesenen Überlebensvorteils besteht bei HER-2-überexprimierenden Tumoren (IHC3+ oder IHC2+ und FISH+) eine Indikation für den Einsatz von Trastuzumab in Kombination mit Cisplatin und Fluoropyrimidinen (5-FU oder Capecitabin). • 5-FU • Junge Patienten • Eine Dreifachkombination mit Cisplatin/5-FU und Docetaxel (DCF) führt bei einer jüngeren Patientenpopulation (median 55 Jahre) im Vergleich zu einer Zweifachtherapie mit Cisplatin/5-FU zu einem statistisch signifikanten Überlebensvorteil, ist jedoch mit einer höheren Rate an Toxizitäten verbunden. o Supportive • Fatigue Bewegung • Diahhroe Von chemo • Loperamid Clostridium • Vancomicin • Oder Metronidazol • Obstipation Laxativen • Ubelkeit Erbrechen 24 h nach Chemotherapie • Serotonin Inchibitors • Granisetron; 2 mg p.o./1mg i.v. Ondansetron; 16-24 mg p.o./8 mg i.v. Palonosetron; 0,25 mg i.v. Tropisetron; 5 mg p.o./i.v. Dolasetron; 200 mg p.o./100 mg i.v. + Steroid Dexamethason; 12 mg p.o/i.v. + NK-1-RA Aprepitant; 125 mg p.o. oder Fosaprepitant 115 mg i.v. 24 h -5 tage • Substanz 5 • Steroid Dexamethason; 8 mg p.o/i.v. Tag 2-4 + NK-1-RA Aprepitant; 80 mg p.o. Tag 2-3 • Mukositis • Hand-Fuß-Syndrom Ausloser • Fluorouracil • Capecitabin • Anaemie Hb <10 • Erythropoetin • Fe Hb <8 • Transfusion • Neutropenie Ab Therapie • Nicht empfohlen >38 • Orale therapie • Amoxycillin clavolunat • Ciprofloxacin • Verschlechterung • Tasozin • Ceftazidim • Meronem • Kein Fieber • Nach 3 tage absetzen der Therapie Mittleres Risiko • Tasozin • Ceftazidim • Meronem • Splenektomie Impfungen • Pneumococus • Hemophylus • Meningokokkus |
|
|
Nachsorge und Rehabilitation o
|
o symptomorientierte Nachsorge
• Grunde 1. Um Funktionsstörungen zu entdecken in Verbindung mit einem Rezidiv oder als benigne Komplikationen der Behandlung 2. Um den Ernährungszustand zu beurteilen und Ernährungsprobleme zu handhaben 3. Um psychische Unterstützung anzubieten für den Patienten und die Familie, mit angemessenen medizinischen Maßnahmen in Liaison mit Palliativmedizin 4. Um die Prüfung der Behandlungsergebnisse zu vereinfachen o Untersunchungen • Anamnese • Befund Gewicht, • Tu marker Die routinemäßige Bestimmung von Tumormarkern wird in der Nachsorge nicht empfohlen. • Labor Eisen Transferrin, Transferrin-Sättigung Vitamin B 12 im Serum Bestimmung von Blutbild o Substitutionen nach Gastrektomie • B12 MCV und der Vitamin-B12 Spiegel nach 3 Monaten oder bei Symptomen bestimmt werden • Bei einer megaloblastären Anämie erfolgt eine parenterale Vitamin-B12-Substitution mit Hydroxycobalamin 1 mg. Initial 6 Injektionen innerhalb von 2-3 Wochen, dann eine Injektion alle 6 Monate zur Erhaltungstherapie. • Follsaure Folsäuremangel werden 5 mg täglich p.o. über 4 Monate substituiert • Pancreasenzymen Bei Fettstuhlen Creon 50 000 3x o Rehabilitation • Nach Abschluss der Primärtherapie sollte eine Anschlussheilbehandlung bei allen rehabilitationsfähigen Patienten angeboten werden. o Psychoonkologie • Das psychische Befinden und psychische Störungen der Patienten sollen im gesamten Krankheitsverlauf wiederholt ermittelt werden. • Depression Fragen 1. Fühlten Sie sich im letzten Monat häufig niedergeschlagen, traurig, bedrückt oder hoffnungslos? 2. Hatten Sie im letzten Monat deutlich weniger Lust und Freude an Dingen, die Sie sonst gerne tun? • Alle Patienten mit Magenkarzinom sollen von ihren medizinischen Behandlern (Ärzten/Pflegekräften)über die Verfügbarkeit professioneller psychischer Unterstützung bzw. Mitbehandlung informiert werden. o Lebenqualitat • Fragen EORTC-QLQ−C30 FACT−Skalen SF−36 Health Survey Short Form mit 36 Items o Komplementäre Therapie • Patienten sollten nach ihrer Nutzung von komplementären und alternativen Therapien befragt werden. |
|
|
Prognose o
|
o Todesursache
• Sepsis • Kachexie 5-25% |
|
|
Postoperative Komplikationen o
|
o Früh Dumping
o Spätdumping o Abführende Schlinge • Grund Obstruktion • Narbe im mesokolon • Peptische Ulkus • Hernienbildung • Mobilität Probleme vagus denervation • Klinik Erbrechen • Diagnostik Magen Darmpassage Gastroskopie Computertomographie • Therapie Chirurgisch o Syndrom der zuführende Schlinge o Alkalische Refluxesophagitis o Ulkus peptikum jejuni o Karzinom der operierten Magen o Stresläsionen |
|
|
Ein serologisches Screening der asymptomatischen Normalbevölkerung sollte o
|
nicht Durchgeführt werden.
|
|
|
Die fokale Atrophie und intestinale Metaplasie müssen o
|
nicht endoskopisch überwacht Werden.
|
|
|
Ein bevölkerungsbezogenes endoskopisches Screening zum Nachweis von Magenfrühkarzinomen wird für Deutschland o
|
nicht empfohlen.
|
|
|
Bezüglich einer möglichen endoskopischen Überwachung von Patienten mit Reseziertem Magen lässt sich aus den existierenden Daten o
|
keine Empfehlung ableiten.
|
|
|
Protonenpumpeninhibitoren (PPI) das Risiko für ein Magenkarzinom o
|
Es gibt keine gesicherten klinischen Hinweise, dass Protonenpumpeninhibitoren (PPI) das Risiko für ein Magenkarzinom erhöhen.
|
|
|
ASS oder NSAR zur Prophylaxe des Magenkarzinoms o
|
ASS oder NSAR sollten nicht zur Prophylaxe des Magenkarzinoms angewendet
werden. |
|
|
Gastric epithelial polyps o
|
• Adenomatous gastric polyps are at increased risk for malignant transformation and should be resected completely. Hyperplastic polyps have a rare malignant potential. Endoscopic polyp appearance cannot differentiate histologic subtypes; therefore, biopsy or polypectomy is recommended when a polyp is encountered.
• Polypoid defects of any size detected radiographically should be evaluated endoscopically, with biopsy and/or removal of the lesions. • Polyps should be endoscopically excised whenever feasible and clinically appropriate. If endoscopic polypectomy is not possible, a biopsy of the polyps should be performed, and if adenomatous or dysplastic tissue is detected, referral for surgical resection should be considered. If representative biopsy samples are obtained and the polyp is nondysplastic, no further intervention is necessary. If it is felt that endoscopic biopsy cannot sufficiently exclude the presence of dysplastic elements, referral for surgical resection is reasonable in polyps that cannot be removed endoscopically. • When multiple gastric polyps are encountered, a biopsy of the largest polyps should be performed or they should be excised, and representative biopsy specimens should be taken from some others. Further management should be based on histologic results. • Surveillance endoscopy one year after removing adenomatous gastric polyps is reasonable to assess recurrence at the prior excision site, new or previously missed polyps, and/or supervening early carcinoma. If the results of this examination are negative, repeat surveillance endoscopy should be repeated no more frequently than at three- to five-year intervals. Follow-up after resection of polyps with high-grade dysplasia and early gastric cancer should be individualized. • No surveillance endoscopy is necessary after adequate sampling or removal of nondysplastic gastric polyps. |
|
|
Gastric metaplasia and dysplasia o
|
• Endoscopic surveillance for gastric intestinal metaplasia has not been extensively studied in the United States and therefore cannot be uniformly recommended.
• Patients [with gastric metaplasia or dysplasia who are] at increased risk for gastric cancer due to ethnic background or family history may benefit from surveillance. • Endoscopic surveillance should incorporate a topographic mapping of the entire stomach. • Patients with confirmed high-grade dysplasia are at significant risk for progressing to cancer and should be considered for gastrectomy or local (eg, endoscopic) resection. |
|
|
Pernicious anemia and gastric carcinoid tumors o
|
• A single endoscopy should be considered to identify prevalent lesions (gastric cancer, carcinoid tumors) in patients with pernicious anemia, but there are insufficient data to support routine subsequent endoscopic surveillance for these patients.
• Surveillance of carcinoid tumors is controversial and should be individualized to the patient. |
|
|
Postgastric surgery o
|
• There are insufficient data to support routine endoscopic surveillance for patients with previous partial gastrectomy for peptic ulcer disease.
• Because gastric surgeries are performed for peptic ulcer disease, an index endoscopy should be performed to establish the presence of H. pylori infection, chronic gastritis, and/or intestinal metaplasia. • If surveillance is considered, it should be initiated after an interval of 15 to 20 years. Multiple biopsies from the anastomosis and gastric remnant should be taken. The threshold should be low to endoscopically evaluate upper gastrointestinal symptoms. |
|
|
Familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (Lynch syndrome) o
|
• Patients with FAP should undergo upper endoscopy with both end-viewing and side-viewing instruments. The optimal timing of initial upper endoscopy is unknown, but could be performed around the time the patient is considered for colectomy, or early in the third decade of life. If no adenomas are detected, another exam should be performed in five years because adenomatous change may occur later in the course of disease.
• Biopsies of gastric polyps in patients with FAP may be performed to confirm they are fundic gland polyps and to assess for dysplasia. Antral polyps are usually adenomas and should be resected. • Patients with HNPCC are at increased risk for the development of gastric and small-bowel cancer. Although there are insufficient data to show a benefit for upper endoscopic surveillance in patients with HNPCC, endoscopic surveillance should be considered. |
|
|
gastric cancers attributable to H. pylori infection o
|
Approximately 36 and 47 percent of all gastric cancers in developed and developing countries, respectively, are solely attributable to H. pylori infection. This accounts for almost 350,000 gastric cancers annually worldwide.
|
|
|
CLINICAL FEATURES o
|
• Weight loss usually results from insufficient caloric intake rather than increased catabolism and may be attributable to anorexia, nausea, abdominal pain, early satiety, and/or dysphagia.
• When present, abdominal pain tends to be epigastric, vague and mild early in the disease but more severe and constant as the disease progresses. • Dysphagia is a common presenting symptom in patients with cancers arising in the proximal stomach or at the esophagogastric junction. • nausea • Occult gastrointestinal bleeding with or without iron deficiency anemia is not uncommon, while overt bleeding (ie, melena or hematemesis) is seen in less than 20 percent of cases. • The presence of a palpable abdominal mass is the most common physical finding and generally indicates long-standing, advanced disease • A pseudoachalasia syndrome may occur as the result of involvement of Auerbach's plexus due to local extension or to malignant obstruction near the gastroesophageal junction. • Approximately 25 percent of patients have a history of gastric ulcer. • All gastric ulcers should be followed to complete healing, and those that do not heal should undergo resection |
|
|
Signs of tumor extension or spread o
|
• feculent emesis or passage of recently ingested material in the stool can be seen with malignant gastrocolic fistula,
• colonic obstruction may occur. • The most common metastatic distribution is to the liver, peritoneal surfaces, and nonregional or distant lymph nodes. • Less commonly, ovaries, central nervous system, bone, pulmonary or soft tissue metastases occur. • Since gastric cancer can spread via lymphatics, the physical examination may reveal a left supraclavicular adenopathy (a Virchow's node) which is the most common physical examination finding of metastatic disease, a periumbilical nodule (Sister Mary Joseph's node), or a left axillary node (Irish node). • Peritoneal spread can present with an enlarged ovary (Krukenberg's tumor) or a mass in the cul-de-sac on rectal examination (Blumer's shelf). • However, there are patients with ovarian metastasis without other peritoneal disease. • Ascites can also be the first indication of peritoneal carcinomatosis. • A palpable liver mass can indicate metastases, although metastatic disease to the liver is often multifocal or diffuse. Liver involvement is often, but not always, associated with an elevation in the serum alkaline phosphatase concentration. Jaundice or clinical evidence of liver failure is seen in the preterminal stages of metastatic disease [7]. |
|
|
Paraneoplastic manifestations o
|
• Dermatologic findings may include the sudden appearance of diffuse seborrheic keratoses (sign of Leser-Trelat)
• acanthosis nigricans • microangiopathic hemolytic anemia • membranous nephropathy • hypercoagulable states (Trousseau's syndrome) • Polyarteritis nodosa has been reported as the single manifestation of an early and surgically curable gastric cancer |
|
|
TNM Staging o
|
TX Primärtumor kann nicht bestimmt werden.
T0 Keine Evidenz für einen Primärtumor Tis Carcinoma in situ: Intraepithelialer Tumor ohne Invasion der Lamina propria T1 Infiltration der Lamina propria oder der Tela submucosa (Synonym: Frühkarzinom) T1a Infiltration der Lamina propria oder Lamina muscularis mucosae T1b Infiltration der Tela submucosa T2 Infiltration der Tunica muscularis T3 Infiltration des subserösen Bindegewebes ohne Invasion des visceralen Peritoneums oder benachbarter Strukturen. T3 schließt auch Tumoren ein, welche sich entlang des gastrocolischen oder gastrohepatischen Ligaments ausbreiten, sowie das Omentum majus oder minus erreichen, ohne Durchdringung des visceralen Peritonuems, welche diese Strukturen umgibt. T4 Infiltration von Nachbarorganen (Milz, Colon transversum, Leber, Zwerchfell, Pancreas, Bauchwand, Nebenniere, Niere, Dünndarm oder Retroperitoneum) T4a Infiltration der Serosa (viscerales Peritoneum) T4b Infiltration von Nachbarorganen (Milz, Colon transversum, Leber, Zwerchfell, Pancreas, Bauchwand, Nebenniere, Niere, Dünndarm oder Retroperitoneum) NX Befall lokaler Lymphknoten nicht beurteilbar N0 Keine lokalen Lymphknoten befallen N1 Metastasen in ein bis zwei lokalen Lymphknoten N2 Metastasen in drei bis sechs lokalen Lymphknoten N3 Metastasen in sieben oder mehr lokalen Lymphknoten M0 Keine Fernmetastasen nachgewiesen M1 Fernmetastasen Stadieneinteilung des Magenkarzinoms Stadium 0 Tis Stadium IA T1 N0 M0 Stadium IB T1 N1 M0 T2 N0 M0 Stadium IIA T1 N2 M0 T2 N1 M0 T3 N0 M0 Stadium IIB T1 N3 M0 T2 N2 M0 T3 N1 M0 T4a N0 M0 Stadium IIIA T2 N3 M0 T3 N2 M0 T4a N1 M0 Stadium IIIB T3 N3 M0 T4a N2 M0 T4b N0, N1 M0 Stadium IIIC T4a N3 M0 T4b N2, N3 M0 Stadium IV Jedes T Jedes N M1 |
|
|
Hereditary diffuse gastric cancer (HDGC) is o
|
an inherited form of diffuse type gastric cancer. Germline mutations of the CDH1 gene, located on chromosome 16q22.1
The end result is loss of expression of the cell adhesion molecule E-cadherin. (See 'Molecular genetics' above.) |
|
|
HDGC is inherited as an o
|
autosomal dominant trait with high penetrance.
|
|
|
The lifetime cumulative risk for advanced gastric cancer in individuals with a germline CDH1 mutation is o
|
>80 percent in both men and women.
|
|
|
Affected patients generally develop gastric cancer at an average age of o
|
38 years.
|
|
|
Women in HDGC families are also at high risk of developing o
|
lobular breast cancer. They should be referred to a high-risk breast cancer clinic and considered for enhanced breast cancer screening.
|
|
|
Prophylactic total gastrectomy o
|
is the recommended approach in patients who are carriers of a germline CDH1 mutation.
The appropriate age at which to perform gastrectomy is debated. |
|
|
Annual surveillance endoscopy with random biopsies may be considered for patients who o
|
receive a recommendation for prophylactic gastrectomy, but who decide to postpone or refuse the procedure due to young age, fertility concerns, or fear of surgery with accompanying complications. Another scenario in which endoscopic surveillance may be considered is in individuals with mutations of undetermined significance, and in those in whom a mutation cannot be identified in the index case. However, in all cases, patients should be counseled as to the focal nature of these endoscopically invisible lesions, and the possibility that they will not be detected by the surveillance procedure.
|
|
|
POSTTREATMENT CANCER SURVEILLANCE o
|
• History and physical examination every three to six months for one to three years, then every six months for years four and five, then annually.
• CBC and chemistry profile, as clinically indicated • Radiologic imaging or endoscopy, as clinically indicated • Monitor for vitamin B12 deficiency in surgically treated patients and treat as indicated |
|
|
TREATMENT OF RECURRENT DISEASE o
|
• Curative resection is not often attempted in patients with recurrent disease, although there are a few case series that describe long-term survivors
• While these results suggest that salvage surgery may contribute to prolonged survival, the opportunity to resect recurrent gastric tumors is infrequent at best. • This approach should be restricted to highly selected fit patients with an isolated local recurrence and no evidence of distant spread. • Rather than surgery, most such patients are offered systemic chemotherapy for palliation of symptoms. • Occasionally, local palliative procedures, such as radiotherapy (in patients not previously having received radiotherapy at the site of recurrence), are needed for symptom control. |
|
|
PALLIATIVE GASTRECTOMY o
|
• may provide effective palliation of symptoms such as pain, nausea, persistent bleeding, or obstruction.
• anemia in a stable patient should not be considered an indication for a palliative gastrectomy. • Radical gastrectomy in this setting provides no survival benefit, but palliative gastrectomy can provide symptomatic relief and a possible improvement in survival, although this is controversial. |
|
|
METASTASECTOMY o
|
Hepatic — Hepatic metastasectomy has been performed for the rare patient with isolated gastric cancer liver metastases.
Pulmonary — Pulmonary metastasectomy for metastatic gastric cancer can potentially result in long-term survival in a highly selected group of patients. However, this approach should be reserved for those patients who present with small isolated lesions after a prolonged disease-free interval. |
|
|
Surgery o
|
• Surgery may be required as a component of the staging evaluation for gastric cancer, for potentially curative treatment of localized disease, or for palliation in cases of advanced disease.
• Complete surgical eradication of a gastric tumor with resection of adjacent lymph nodes represents the best chance for long-term survival. |
|
|
The choice of operation for gastric cancer o
|
• depends upon the location of the tumor within the stomach, the clinical stage, and the histologic type.
• The major surgical considerations include the extent of luminal resection (total versus subtotal gastrectomy) and the extent of lymph node dissection. • Total gastrectomy is usually performed for lesions in the proximal (upper third) of the stomach, while • distal subtotal gastrectomy (with resection of adjacent lymph nodes) appears to be sufficient for lesions in the distal (lower two-thirds) of the stomach. • Tumors of the proximal stomach that do not invade the esophagogastric junction (EGJ) can be approached by either a total gastrectomy or a proximal subtotal gastrectomy. |
|
|
The optimal extent of lymphadenectomy o
|
• While several randomized trials have failed to show an overall survival benefit from a D2 compared to a D1 resection, excess morbidity and mortality were clearly associated with the use of splenectomy and distal pancreatectomy to achieve complete node dissection.
• The most recent report of the Dutch trial suggests that cancer-specific mortality rates are significantly lower in patients who undergo a D2 rather than a D1 lymphadenectomy. • We suggest a D2 rather than a D1 resection for patients who are undergoing potentially curative resection of a gastric cancer (Grade 2B). • Perioperative mortality rates under 2 percent should be expected at centers with higher patient volume. • In contrast, there is no evidence that a D3 (paraaortic lymphadenectomy) confers a survival benefit over D2 dissection, and it is associated with greater mortality. We recommend that a D3 dissection not be considered for surgical treatment of gastric cancer (Grade 1B). (See 'D2 versus D3 dissection' above.) |
|
|
Local palliation for advanced gastric cancer o
|
• The majority of patients with gastric cancer will require palliative treatment at some point in the course of their disease.
• Cytotoxic chemotherapy is the most effective treatment modality for metastatic disease, but it is frequently inadequate for palliation of local symptoms such nausea, pain, obstruction, perforation, or bleeding from a locally advanced or locally recurrent primary tumor. • Most patients require multidisciplinary management using endoscopic, surgical, radiotherapeutic or other approaches. • Although effective, palliative resection for patients with metastatic gastric cancer is only rarely performed and reserved for extreme cases where less invasive methods cannot be used. • For patients with obstructive symptoms, we recommend endoscopic placement of a stent rather than palliative surgery (Grade 1B). • Endoscopic stenting has a similar success rate as surgical palliation (with approximately 90 percent of patients improving clinically) but is associated with less morbidity, procedure-related mortality, and cost. • External beam radiation therapy (RT) can control pain, bleeding, and obstruction in patients with localized but unresectable gastric cancer, but responses may be delayed. • Another option to palliate dysphagia due to obstruction in patients with esophageal or gastric cardia tumors is endoscopic laser ablation. |
|
|
There are two distinct types of gastric adenocarcinoma, o
|
intestinal (well-differentiated) and diffuse (undifferentiated), which have distinct morphologic appearance, pathogenesis, and genetic profiles
• A lack of adhesion molecules in diffuse carcinomas allows the individual tumor cells to grow and invade neighboring structures without the formation of tubules or glands. • Diffuse type cancers are highly metastatic and characterized by rapid disease progression and a poor prognosis. • The main carcinogenic event is loss of expression of E-cadherin, a key cell surface protein for establishing intercellular connections. • In direct contrast, the pathogenesis of intestinal-type gastric cancers is less well defined. • follow a multistep progression that is usually initiated by H. pylori infection. |
|
|
PRECURSOR LESIONS FOR INTESTINAL TYPE CANCERS o
|
• Longstanding chronic superficial gastritis caused by chronic H. pylori infection, pernicious anemia, or possibly a high salt diet leads eventually to chronic atrophic gastritis and intestinal metaplasia.
• Gastric atrophy is accompanied by a loss of parietal cell mass and therefore a reduction in acid production (hypochlorhydria or achlorhydria), a decrease in luminal ascorbic acid (vitamin C) levels, and a compensatory increase in serum gastrin, a potent inducer of gastric epithelial cell proliferation. • Similarly, gastric resection results in hypo- or achlorhydria, secondary hypergastrinemia, and bile reflux, especially after a Billroth II anastomosis. The increase in gastric pH would permit colonization of bacteria capable of converting dietary nitrates to potent mutagenic N-nitroso compounds. • Chronic inflammation results in epithelial cell damage with increased free radical generation, a further reduction in luminal ascorbic acid levels, and increased cell turnover. • Atrophic gastritis — cause gastric atrophy are associated with an increased risk of both cardia and non-cardia gastric adenocarcinomas • 3 to 18 times greater than an age-matched population. • Intestinal metaplasia • Dysplasia • Most patients diagnosed with high-grade dysplasia of the gastric mucosa either already have or soon develop gastric cancer. • In gastrectomy specimens for gastric cancer, 20 to 40 percent of patients have associated dysplasia |
|
|
PRECURSOR LESIONS FOR DIFFUSE TYPE CANCERS o
|
In contrast to intestinal type gastric cancers, diffuse type gastric cancers have no clearly defined precancerous lesion.
|
|
|
ENVIRONMENTAL RISK FACTORS o
|
• Diet
• Salt and salt-preserved foods • Nitroso compounds • Fruits, vegetables, and fiber • Folate • Obesity • Smoking • Helicobacter pylori • Influence of salt and intake of salted foods • Possible protective effect of NSAIDs • Epstein-Barr virus • Alcohol — A consistent association between alcohol consumption and the risk of gastric cancer has not been demonstrated • Socioeconomic status • Gastric surgery • Reproductive hormones |
|
|
HOST-RELATED FACTORS o
|
• Blood group — . Individuals of blood group A have been known for decades to show an approximately 20 percent excess of gastric cancer than those of group O, B, or AB
• Familial predisposition • Hereditary diffuse gastric cancer • Genetic polymorphisms • Gastric polyps • Hypertrophic gastropathy and immunodeficiency syndromes • Gastric ulcer • Pernicious anemia |
|
|
AEG Chemotherapie o
|
• Most clinicians now treat EGJ and proximal gastric cancers as esophageal cancers, using preoperative chemoradiotherapy.
|
|
|
For patients with non-cardiac gastric cancer o
|
• adjuvant chemoradiotherapy for those with resected stage IIA disease or higher
• One cycle of 5-FU (425 mg/m 2 per day) and leucovorin calcium (20 mg/m2 per day) daily for five days. • This is followed one month later by 45 Gy (1.8 Gy/day) of RT given with FU (400 mg/m2 per day) and leucovorin calcium (20 mg/m2 per day) on days 1 through 4 and the last three days of RT. • As an alternative, current randomized trials are using continuous infusion FU at a dose of 200 mg/m2/day during RT. Two more five-day cycles of chemotherapy (FU 425 mg/m 2 per day and leucovorin calcium 20 mg/m2 per day) are given at monthly intervals beginning one month after completion of radiation. • As an alternative, others replace the • chemotherapy cycles with either weekly 5-FU plus leucovorin (the Roswell Park regimen), • short-term infusional 5-FU plus leucovorin (the de Gramont regimen), or • capecitabine alone |
|
|
Perioperative Chemotherapie o
|
combined preoperative (three courses) and postoperative (three courses) ECF (epirubicin, cisplatin, and FU,
|
|
|
Palliative Chemotherapie o
|
First-line chemotherapy
• In randomized trials, the ECF ( epirubicin, cisplatin, infusional 5-FU, (table 4)) and DCF (TCF, docetaxel, cisplatin, infusional 5-FU) combinations have emerged as standard regimens for first-line treatment. • A major problem with these regimens is the need for central venous access and an ambulatory infusion pump. • Data from the REAL-2 trial suggest that outcomes are comparable if capecitabine is substituted for infusional 5-FU, and when oxaliplatin is substituted for cisplatin in the ECF regimen • When both oxaliplatin and capecitabine are substituted in the ECF regimen, outcomes are at least as good as with ECF, and trend towards better. • For these reasons, we suggest epirubicin, oxaliplatin and capecitabine (EOX) rather than ECF or TCF for first-line treatment (Grade 2B). • While the use of capecitabine allows patients to avoid infusion pumps and a central venous catheter, the costs of capecitabine and oxaliplatin are significantly higher than with 5-FU and cisplatin, and toxicity is not necessarily less. • FOLFOX is another reasonable option. • Patients with gastric cancer who are potential candidates for trastuzumab should have their tumors assayed for the presence of HER2 overexpression. • We suggest the addition of trastuzumab to chemotherapy in patients with HER2-positive tumors (as defined by 3+ immunohistochemical staining or FISH positivity), as long as they do not have a contraindication to trastuzumab (Grade 2B). • For elderly patients or those with a poor performance status, we suggest leucovorin-modulated 5-FU alone or single agent capecitabine (Grade 2B). • Other reasonable alternatives include single agent irinotecan, or low-dose weekly taxanes. Second line chemotherapy • For patients who retain an adequate performance status, utilization of other active agents not used in the first-line regimen is reasonable, either in combination or as serial single agents. • Quality of life and minimization of side effects are key considerations when choosing the therapeutic approach. Intraperitoneal chemotherapy |
