Benign and malign diseases of Stomach Prof. Dr. Öge TAŞCILAR

2

Esophagus/Stomach Junction stratified squamous non-keratinized epithelium Stomach: Simple columnar epithelium

MİDE Mukoza Submukoza Muskularis Propria Seroza İntraepitelyal Mukoza Bazal Membran Lamina Propria Muskularis Mukoza

Fonksiyon: MİDE Alınan gıdaların sindirimi ve emilimi Reseptif relaksasyon ve gastrik adaptasyon İntragastrik basınç düşer. 100cc-------------1500cc

Mallory-Weiss Sendromu MİDE Mallory-Weiss Sendromu Kusma ÖG bileşke Mukoza submukoza yırtık ve kanama Endoskopi Alkol,diyabet,gebelik, üremi, Tam kat olursa Booerhaave sendromu

MİDE Bezoarlar Midede oluşan yabancı cisimler. Trikobezoar-fitobezoar Mide operasyonu sonrası Antrumun öğütücü işlevinin kaybolması HCL azalmasına bağlı Candida Albicans bezoar Tanı: Radyoloji-endoskopi Tedavi:Endoskopik-Cerrahi

MİDE Menetrier Hastalığı Hipertrofik mukozal gastropati Fundus ve korpusta dev rugalar Foveolar hiperplazi Hipoklorhidri ve Hipoalbüminemi 50> erkekler Epigastrik ağrı, kilo kaybı, (özellikle protein) , kanama, diare, ödem Medikal tedavi PPI Destek tedavisi Çok ciddi olgularda rezeksiyon

Gastritis Acute gastritis often due to chemical injury (alcohol drugs)

Acute gastritis Drugs (non-steroidal anti-inflammatory drugs NSAID), alcohol cause acute erosion (loss of mucosa superficial to muscularis mucosae). Can result in severe haemorrhage

Chronic gastritis ABC A – autoimmune(associated with vitamin B12 malabsorption (pernicious anaemia) B – bacterial (helicobacter) C – chemical(bile reflux, drugs)

Autoimmune chronic gastritis Autoantibodies to gastric parietal cells Hypochlorhydria/achlorhydria Loss of gastric intrinsic factor leads to malabsorption of vitamin B12 with macrocytic,megaloblastic anaemia

Helicobacter pylori Adapted to live in association with surface epithelium beneath mucus barrier Causes cell damage and inflammatory cell infiltration In most countries the majority of adults are infected

Chemical gastritis Commonly seen with bile reflux (toxic to cells) Prominent hyperplastic response (inflammatory cells scanty) With time – intestinal metaplasia

Peptic ulcer disease A surface breach of mucosal lining of GI tract occurring as a result of acid and pepsin attack Sites: Duodenum (DU) Stomach (GU) Oesophagus Gastro-enterostomy stoma Related to ectopic gastric mucosa (e.g. in Meckel’s diverticulum)

Chronic peptic ulcer Complex epidemiology DU most common in Europe, GU in Japan Incidence of DU declining, GU stable

Pathogenesis In normal acid/pepsin attack is balanced by mucosal defences Increased attack by hyperacidity Weakened mucosal defence – the major factor (H. pylori related)

MİDE DU son yıllarda azalmaktadır. Sigara azalması HP etkin korunma H2 blokör, PPI Mukoza saldırgan faktörler etkili HP, NSAİ, ZES

MİDE Duodenal Ülser: Duodenal HCO3 sekresyonu azalmış Gece asit sekres. Artmış Duodenal asit yükü atmış Bazal ve postbrandial gastrin artmış PH kitlesi artmış. Tamamına yakın HP gastrit saptanmıştır.

Morphology of peptic ulcers Clean, non-elevated edge Granulation tissue base (floor) Underlying fibrosis

MİDE Klinik: Yanıcı, kemirici, açlık ağrısı. Epigastrium Antiasit ve gıda ile hafifler. Mevsimsel bir ağrı. İlkbahar, sonbahar, stress dönemleri Penetre olursa ağrı özellikleri değişir.

MİDE Tedavi: Anamnez, Radyoloji Endoskopi, biyopsi Medikal tedavi Antiasit Sükralfat H2 blokör PPI Prostoglandin analogları

MİDE DÜ Cerrahi Tedavi: BTV-PP BTV-Distal gastrektomi+GJ PGV

MİDE Mide Ülseri MÜ 5 tip vardır. Tip 1: En sık %60. Küçük kurvatur. Tip 2:%20-25 Duodenuma yakın(Kombine gastrik, duodenal) Tip 3: %20. Prepilorik antrum Tip 4: GÖ bileşkeye yakın Tip 5: Diffüz Alkol, NSAİ

Benign gastric ulcer (B) Figure 7-10. Benign gastric ulcer. A, Barium radiograph demonstrates a lesion on the angularis atypical for a benign lesion because the angularis is retracted. The ulcer margin is also not well demarcated. No abnormal rugal folds surround the lesion. Radiographically, a malignant lesion could not be excluded. B, Typical endoscopic appearance of a benign gastric ulcer. The ulcer is on the angularis–the most common location for a gastric ulcer–and is well circumscribed without any associated mass effect. The surrounding mucosa is mildly erythematous and without nodularity.

MİDE Mide Ülseri MÜ Cerrahi tedavi: Tip 2-3 duodenal ülser gibi tedavi Tip1: Ülseri içine alan distal gastrektomi+GJ

Complications of peptic ulcer Perforation leading to peritonitis Haemorrhage by erosion of vessel in base Penetration of surrounding organ (liver/pancreas) Obstruction (by scarring) – pyloric stenosis (Cancer – rare event in true peptic ulcer)

Complications of peptic ulcer Kanama: DÜ kanama Kanayan yere transfiksiyon+BTV+PP Genç veya kronik olgularda: Kanayan yere transfiksiyon+ Ülseri içeren antrektomi+BTV

Complications of peptic ulcer Kanama: MÜ kanama: Tip1: Ülseri içine alan distal gastrektomi+GJ Tip 2-3: DÜ kanamasındaki aynı tedavi

Complications of peptic ulcer Delinme DÜ Graham usulü Duodenorafi+PPI Graham usulü Duodenorafi+ PGV

Complications of peptic ulcer Delinme MÜ Tip1: Ülseri içine alan distal gastrektomi+GJ veya omental patch. Tip 2: BTV+Antrektomi Tip 3: BTV+Antrektomi

BENIGN__ 10% MALIGNANT__90% BENIGN Polyps Lipomas Leiomyomas NEOPLASMS OF STOMACH BENIGN__ 10% MALIGNANT__90% BENIGN Polyps Lipomas Leiomyomas 35

NEOPLASMS OF STOMACH MALIGNANT Adenocarcinoma 95% Lymphoma 4% Others 1% (sq.cell ca, angiosarcoma, carcinosarcoma, Gist)

Less common gastric neoplasms Gastrointestinal stromal tumour (GIST) Lymphoma Neuroendocrine (carcinoid) tumours

Gastrointestinal stromal tumours (GIST) Mesenchymal neoplasms Derived from interstitial cells of Cajal (pacemaker cells controlling peristalsis) Overexpress c-kit oncogene Used as diagnostic aid on tissue A target for therapy with tyrosine kinase inhibitor imatinib (also used in CML)

GIST-spindle cell neoplasm of GI tract

GIST Larger tumours with high mitotic rate tend to behave malignantly Stomach is commonest site

GIST Risk categories were assigned according to current recommended NIH criteria. Tumors <2 cm and<5 mitosis per 50 high-power fields (HPF) were classified as very low risk. Tumors ranging from 2 to 5 cm and having <5 mitoses/50 HPF were classified as low risk.

Tumors <5 cm but having 6 to 10 mitoses/50 HPF were intermediate risk, as were tumors from 5 to 10 cm with <5 mitoses/50 HPF. Tumors >5 cm with >5 mitoses/50 HPF was defined as high risk, as was any tumor >10 cm or any tumor with >10 mitoses/50 HPF.

GASTRIC STROMAL TUMOURS PRESENTATION; Mass abdomen Upper GI bleeding Obstruction PATHOLOGY; Difficult to ascertain benign or malignant nature Size & Histology is the criteria TREATMENT; Surgical resection Lymph node resection not necessary. 43

MİDE LENFOMA NHL klasik olarak lenf nodlarından gelişir. Ama NHL %30 olguda ekstranodal(Solid organ kaynaklı) olarak gelişebilir. GI sistem tüm NHL %20

MİDE LENFOMA GI lenfoma; oral kaviteden rektuma En sık; Mide Sonra ince barsak Kolon Pankreas

MİDE LENFOMA NHL, ekstranodal lenfoma ve GI lenfomanın en sık görülen tipi diffüz B hücre lenfoması. MALT lenfoma Burkitt lenfoma T- hücre lenfoma

Gastric lymphoma Malignant neoplasm of mucosa associated lymphoid tissue (MALT) A (usually) low grade B-cell (marginal cell) lymphoma

MİDE LENFOMA GASTRİK LENFOMA DLBCL (%55)ve MALT tipi lenfoma(40), %3 Burkitt Lenfoma Antrum ve distal mide Proksimal yerleşebilir. Karın ağrısı, erken doyma Bulantı, kusma, halsizlik Abdominal dolgunluk Kronik kan kaybı, anemi melena

Gastric lymphoma (maltoma) Neoplastic cells infiltrate the epithelium (lymphoepithelial lesions) Strongly associated with chronic H. pylori and can be cured by eliminating infection.

MİDE LENFOMA Ann Arbor Musshoff Modifikasyonu: IE: Diyafragmanın bir tarafında bir organda veya tek lenf nodu bölgesi IE1: Mukoza-submukoza IE2: Muskularis invaze

MİDE LENFOMA Ann Arbor Musshoff Modifikasyonu: IIE: Ek olarak Diyafragmanın bir tarafında lenf nod tutulumu IIE1: Bölgesel lenf nodlarında IIE2: Uzak lenf bölgelerinde

MİDE LENFOMA Ann Arbor Musshoff Modifikasyonu: IIIE: Diyafragmanın her iki tarafında organ ve/veya lenf nod tutulumu IVE: Ekstra GI organ tutulumu

MİDE LENFOMA Tedavi HP tedavi edilmeli. Bir zamanlar cerrahi Şimdi Konservatif, bazı olgularda cerrahi Low grade lenfoma(MALT) HP eradikasyonu, KRT, High Grade: Antihelikobakter tedaviye cevap vermeyen erken evre PGL, ileri evre lenfoma, diffüz büyük hücreli lenfoma ise cerrahi tedavi KT-RT Residual hastalık: KT-cerrahi

Neuroendocrine tumours Carcinoids are tumours of resident neuroendocrine cells in gastric glands Usually seen in context of chronic atrophic gastritis (driven by gastrin) Clinical behaviour variable

GASTRIC CANCER 5 year survival 5% Early diagnosis is key to success Only treatment to cure the disease is,SURGERY INCIDENCE 15/100000 per year in UK In japan 70/100000 per year Men<women Incidence is falling 1% over year in carcinoma arising in body and distal stomach which is common in low socioeconomic group There is increase in proximal gastric cancer 55

Carcinoma of the stomach The second most common fatal malignancy in the world (after lung cancer) Commonest in Far East (Japan) Incidence declining High mortality unless disease detected early

SITES OF GASTRIC CANCER 30 years before Present days 57

ETIOLOGY 1.HELICOBACTER PYLORI CA of body & distal stomach Gastritis Gastric atrophy Intestinal metaplasia 2.PERNICIOUS ANEMIA 3.GASTRIC POLYPS 4.Pt. with surgery of peptic ulcer disease Billroth II or polya gastrectomy Gastroenterostomy Pyloroplasty 4 times increased risk 58

5.Cigarette smoking &dust ingestion 6.Diet Consumption of potatoes,pickled vegetables,dried/salted fish & less milk Alcohol ingestion Excessive salt intake Deficiencies of anti oxidants Exposure to N- Nitrosocompounds 7.Familial predisposition Relatives of CA stomach pt. are 4 times more at risk Genetically H-ras, C-erb B2 & APC gene mutations have some role in pathogenesis of CA stomach Blood group A 8.Gastric ulcer 3-5% of cases?? 9. İntestinal metaplazi Tip1,2 ve 3 En tehlikeli olanı Tip 3 59

Helicobacter factors in pathogenesis Some strains are more pathogenic than others. The Cag A (cytotoxic) antigen is one important virulence factor Human variability also plays a part (e.g. individuals who produce high levels of IL-1b in inflammation get pan gastritis and GU, lower levels associated with antral gastritis and DU)

Pathology 1. EARLY GASTRIC CANCER Gastric epithelial cancers are adenocarcinomas sqamous cell carcinomas LAUREN CLASSIFICATION OF GASTRIC CA Diffuse type well differentiated poorly differentiated undifferentiated Intestinal type Others EARLY & ADVANCED GASTRIC CANCER 1. EARLY GASTRIC CANCER cancer limited to mucosa & submucosa with or without involvement of lymph nodes ( T1 , any N) With surgery 5 year survival rate is 90% Further classified by Japanese classification in to 1.Protruding . Elevated . Flat . Depressed 2. Excavating 61

62

ADVANCED GASTRIC CARCINOMA Cancer involving muscularis BORMANN CLASSIFICATION (MACROSCOPIC TYPE) 63

PATHOLOGY MACROSCOPIC CLASSIFICATION Schirrous (lintis plastica) Ulcerative Polypoid Superficial spreading HISTOLOGICALLY (W.H.O) Papillary Tubular Mucin secreting Signet ring cell 64

Clinical Features GASTRIC CANCER Early feeling of fullness after meal Bloating , distention Vomiting Pallor – iron deficiency anemia due to tumour bleed Dysphygia –epigastric fullness or vomiting due to obstrution of gastric outlet Epigastric mass – ¼ of cases Non metastatic effects ; thrombophlebitis Deep venous thrombosis ( by affecting thrombotic & haemostatic mechanism) 65

Trosier sign(virchows node) Ascites Jaundice Trosier sign(virchows node) Sister mary joseph nodule krukenberg tumour Blummer Shelf 66

INVESTIGATIONS BLOOD COMPLETE EXAM. ------ Anemia STOOL EXAM. --- for occult blood in ½ of pts. CARCINOEMBRYONIC (CEA) LEVEL--- elevated in 65% of cases GASTRIC JUICE ANALYSIS--- 20% are achlorhydric after maximal stimulation DOUBLE CONTRAST BARIUM MEAL--- mucosal irregularities and to assess the size , shape, margins of lesions GASTROSCOPY & BIOPSY---minimum of 6 biopsies for accuracy --- brush cytology C.T. SCAN ENDOSCOPIC USG LAPAROSCOPY 67

Advanced Gastric CA TYPE (I) 68

Advanced Gastric CA TYPE (II) 69

Advanced Gastric CA TYPE (III) 70

Advanced Gastric CA TYPE (IV) 71

72

73

74

75

Macroscopic Pathology Gross types Polypoid Ulcerative Infiltrative (extreme is linitis plastica – “leather bottle stomach)

Microscopy Intestinal type (forms glands – like cancers of colon and oesophagus) Diffuse type – dissociated tumour cells often containing a mucinous “blob” – signet ring cells

78

STAGING TNM Staging of Gastric CA Tis tumour limited to limited to mucosa without penetration through basement memb into lamina propria T1 Tumour limited to mocosa or mucosa and submucosa T2 Tumour extendind into muscularis propia and may extend into but not through the serosa T3 Tumour penetrates serosa without invadind contiguous strutures T4 Tumour invading adjacent strutures N0 No metastasis to regional lymph nodes N1 Involvement of perigastric lymph nodes within 3cm of primary tumour N2 Involvement of regional lymph nodes more than 3cm from the primary tumour including nodes along left gastric,splenic, celiac and common hepatic arteries N3 Involvement of other nodes such as para-aortic, hepatoduodenal, retropancreatic and mesenteric nodes. M0 No distant metastases M1 Distant metastasis present N1—1-6..REGIONAL NODES INVOLVED N2--- 7-15 NODES INVOLVED N3– MORE THAN 15 NODES INVOLVED 79

MİDE KANSERİNDE CERRAHİ TEDAVİ PRENSİPLERİ JRSGC’ nin Lenf nod klasifikasyonu(1981) 1 Sağ parakardiyal 2 Sol parakardiyal 3 Küçük kurvatur etrafı 4 Büyük kurvatur etrafı N1 5 Suprapilorik 6 Infrapilorik 7 Sol gastrik arter civarı 8 A. Hepatika Kommunis civarı N2 9 Çöliak arter etrafı 10 Splenik hilus 11 Splenik arter boyunca

MİDE KANSERİNDE CERRAHİ TEDAVİ PRENSİPLERİ 12 Hepatoduodenal ligament civarı 13 Pankreas baş ve arkası 14 Mezenter Kökü N3 15 Transvers mezokolon 16 Paraaortik N4 110 Alt torakal paraözefagiyal lenf nodları 111 Diyafragmatik lenf nodları

Lymphatic drainage of stomach and nodal stations by the Japanese classification 82

Regional lymph nodes of stomach 83

CT STAGING OF GASTRIC CA STAGE I Intraluminal mass without wall thickening STAGE II Wall thickening greater than 1 cm STAGE III Direct invasion of adjacent structures STAGE IV Metastatic disease STAGING IA T1 N0 MO IB T1 N1 M0 II T1 N2 M0 III T2 N2 M0 IIIB T3 N2 M IV AnyT Any N M1 85

SPREAD DIRECT : LYMPHATIC : By permeation Emboli Trosier,s sign BLOOD BORN METASTASIS Liver Lung,bones TRANSPERITONEAL SPREAD Indicates incureability Manifests as ascities Krukenberg tumour Sister joseph nodule Blumer,s shelf 86

TREATMENT SURGICAL TREATMENT 1.SURGERY; --curative --palliative 2.RADIOTHERAPY 3.CHEMOTHERAPY SURGICAL TREATMENT Incurable disease is not subjected to radical surgery Evidence of incureability are; --Haematogenous spread --Distant peritoneal involvement --N4 nodal disease & disease beyond N4 nodes --Fixation to structures that can not be removed Cure resection should be considered in remaining pts. 87

Total Gastrectomy 88

Subtotal Gastrectomy 89

3.PALLIATIVE SURGERY; RADIOTHERAPY; CHEMOTHERAPY; In symptoms of obstruction & bleeding Only tumour is removed &GIT continuity is restored by ROUX LOOP Gastric exclusion & oesophagojejunostomy Palliative intubation & stenting (for inoperable cardia tumours) RADIOTHERAPY; Results are disappoiting in CA stomach But have benefits in painful bony metastasis CHEMOTHERAPY; Epirubacin + cispltinium+5-FU Mitomycin C– impregnated charcoal in intraperitoneal route ( in Japan) RELAPSE & METASTASIS; Common site of relapse is Gastric bed Metastasis occur in –intra peritoneal & distal LNs -- liver -- lungs & bones 93