THE PROGRESS AND TREATMENT PERSPECTIVES IN CARCINOMA STOMACH master copy (3).pptx

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1. THE PROGRESS AND TREATMENT PERSPECTIVES IN CARCINOMA STOMACH Prof. Dr. S.P.GAYATHRE M.S.,D.G.O PROFESSOR & HEAD DEPARTMENT OF GENERAL SURGERY GOVT.STANLEY MEDICAL COLLEGE-CHENNAI

2. CA STOMACH Cancer death – 3 rd leading (worldwide) Early gastric Ca – diagnosed in less than 10% . Ia Gastric Ca – 5 year survival 95% Early diagnosis - crucial role. Majority of gastric Ca – diagnosed at advanced stage Poor prognosis

3. WHY DO WE WANT TO DIAGNOSE EARLY ? Why ? Improvement in Survival rate Better patient compliance What helps in an early diagnosis ? Latest techniques – To pick up early lesions thereby improving survival. Nevertheless, surgery - gold standard treatment

4. Flexible endoscopy with tissue biopsy :Gold standard 6-8 biopsies good results. Endoscopic ultrasound : T staging. Drawbacks -operator dependent & <5mmLN not visualised . CECT i.v. with Oral contrast: Accuracy : N > T stage PET-CT - Detects – Occult mets Follow up Diagnostic Laparoscopy: accurate-peritoneal metastasis references: Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy CONVENTIONAL DIAGNOSTIC MODALITIES

5. DIAGNOSTIC ADVANCES

6. NARROW BAND IMAGING Magnifying endoscopy with narrow band imaging Accurate Blue(400-430nm) – Capillaries highlighted( Hb absorbed) Green light(525-555nm) – Penentration good - Dyplastic areas - abnormal microvascular pattern – better highlighted – higher biopsy yield references: Q J Med 2013; 106:117–131 doi:10.1093/qjmed/hcs186 Advance Access Publication 24 October 201 2

7. CHROMOENDOSCOPY Various stains used Sprayed in a mist form Absorptive stain(Lugol’s Iodine) Dysplastic cells - Low glycogen Not stained references: Q J Med 2013; 106:117–131 doi:10.1093/qjmed/hcs186 Advance Access Publication 24 October 2012

8. 2. Contrast stain(Methylene blue) Stains cracks and crevices Dysplastic areas – well visualised references: Q J Med 2013; 106:117–131 doi:10.1093/qjmed/hcs186 Advance Access Publication 24 October 2012

9. 3.Reactive stains(Congo red) Dysplastic cells - decreased acid Do not turn black on Congo red references: Q J Med 2013; 106:117–131 doi:10.1093/qjmed/hcs186 Advance Access Publication 24 October 2012

10. CONFOCAL LASER ENDOMICROSCOPY Optical Biopsy P rovides M agnified, High resolution images C ellular level view of gastric mucosa T argeted biopsies - significantly higher yield

11. LIQUID BIOPSY B ody fluids - blood, urine, saliva, breast milk – contain numerous biomarkers . Most commonly used - Blood BIOMARKERS 1. Cellular 2. Acellular

12. COMPONENTS OF LIQUID BIOPSIES ACELLULAR CELLULAR Circulating tumour cells - Present - peripheral circulation. Shed - primary/metastatic tumour . Eliminated - immune mechanisms / shear forces (ii) Peripheral blood mononuclear cells - T cells NK cells B cells Monocytes. ( i ) Cell free DNA : Hemopoietic origin (ii)Cell derived fragmented DNA high concentrate in serum. (iii) RNA : High sensitivity and tissue specificity. 4) Exosomes : present in all body fluids. 5) Proteins ( Tumour Markers) CEA CA 19-9 CA 125 CA 72-4 Low sensitivity.

13. PLASMA ctDNA Frozen – Stable Gives molecular information - tumour BUFFY COAT CTC’s Viable cells - DNA,RNA Exosomes etc Frozen – Unstable METHODOLOGY CTC’s – Cytological microscopy DNA – Polymerase chain reaction (PCR) and Next generation sequencing

14. ADVANTAGES : Early diagnosis. Monitoring residual disease. Predicting prognosis. Response to treatment. Recurrence monitoring references: Siravegna , G.; Marsoni , S.; Siena, S.; Bardelli , A. Integrating Liquid Biopsies into the Management of Cancer. Nat. Rev. Clin. Oncol. 2017, 14, 531–548 Diagnostics 2018, 8, 75; doi:10.3390/diagnostics8040075 SURVEILLANCE Circulating tumour cells/constituents - in blood – upto 2 weeks post surgery. Persistent rise - after 2 weeks –residual or recurrent disease

15. CONVENTIONAL BIOPSY LIQUID BIOPSY VS references: Siravegna, G.; Marsoni, S.; Siena, S.; Bardelli, A. Integrating Liquid Biopsies into the Management of Cancer. Nat. Rev. Clin. Oncol. 2017, 14, 531–548 Diagnostics 2018, 8, 75; doi:10.3390/diagnostics8040075

16. CHANGING CONCEPTS  Earlier – Extensive surgery Present – Individualised and Evidence based approach Radical surgery En bloc resection Extensive LN Dissection Done selectively references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th edition

17. CONVENTIONAL TREATMENT MODALITIES EMR/ESD Early CA Positive lateral margin – Repeat EMR/ESD Positive vertical margin – Gastrectomy Gastrectomy + D2 lymphadenectomy Open/Lap Expanding Tx – 3cm Prox margin Infiltrative Tx – 5cm prox margin Extensive resection – Omentum /Spleen/Bursa – Not preferred references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th edition ESD

18. Palliative Transarterial embolization Celiac artery – LGA or Gastroepiploic entered Embolised – PVA, Gel foam, Coils Palliative AGJ – Pyloric obstruction Palliative Stenting – Cardia Tumours Palliative RT – Bony mets /Bleeding Tumours references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th edition

19. TREATMENT ADVANCES

20. FUNCTION PRESERVING GASTRECTOMY Includes – Wedge resection ESD + Sentinel node dissection P ylorus-preserving gastrectomy P roximal gastrectomy Indication Early gastric Ca – LN resection not needed M acroscopic resection margin of 2 cm is considered adequate Gastrectomy related complications - Less references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th edition FUNCTIONAL GASTRECTOMY

21.   SENTINEL LYMPHADENECTOMY – ICG IMAGIN G Maps LN – High metabolic activity Yield increased – same operating time Allow local gastric resections with limited LN dissection references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th editions

22. ROBOTIC GASTRECTOMY ADVANTAGES : High-resolution 3-dimensional camera T remor elimination 7 degrees of freedom. R educed postoperative morbidity and faster recovery DISADVANTAGES: Higher cost Longer operating time Steep learning curve references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th editions

23. HIPEC AND CYTO REDUCTIVE SURGERY REVIVAL The notion that peritoneal spread in Gastric Ca is a fatal discovery is gradually being challenged.

24. The goal of CRS removal of all visible peritoneal lesions HIPEC acts on : Free floating cancer cells Peritoneal micromet astases Penetration of drugs - 1−2 mm Drugs – Mitomycin C Cisplatin D oxorubicin Efficacy increased – Hyperthermia – 42 o C Mechanism -Impaired DNA repair Protein denaturation Systemic side effects – limited – blood peritoneal barrier.

25. The National Institute for Health and Care Excellence (NICE) 2021 - UK “ CRS + HIPEC for gastric peritoneal mets should be used as clinical trial only (treatment or preventive)

26. CLINICAL TRIALS - SURGERY KLAS-04 Trial 2023: cT1N0M0 Middle 1/3rd of Stomach Compared Lap pylorus preserving gastrectomy with distal gastrectomy No statistical significance noted JCOG1001 2018 trial showed that patients who underwent bursectomy had a nearly two-fold increased incidence of pancreatic fistula without any survival benefit JCOG1711 2020 compared standard omentum resection versus preservation have shown comparable oncological outcomes, with no difference in survival and peritoneal relapse rates

27. CHEMOTHERAPY FLOT 4 Trial 2019 references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th edition Surgery with Perioperative chemo Fluorouacil/Leucovorin/Oxaliplatin/Docetaxel - 4 cycles before and after surgery VS Results : Perioperative chemo with 4 drug regimen (FLOT 4) - Better survival Surgery with Perioperative chemo Epirubicin/Cisplatin/ Carboplatin or 5 FU - 3 cycles before and after surgery

28. IMMUNOTHERAPY Immune checkpoint inhibitors: Programmed death – PD1 – Pembrolizumab . Programmed death ligand 1 inhibitors – Atezolizumab, Avelumab . Cytotoxic Lymphocyte associated antigen – CTLA 4 – Iplimumab . REFERENCES: 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality,doi: 10.3322/caac.21660 2. Ren W, Yu J, Zhang ZM, Song YK, Li YH, Wang L. Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia. World J Gastroenterol (2013)

29. Keynote Trial – 859 (2023) Immunotherapy complements chemotherapy references: Sabiston book of surgery 21st edition Bailey&love’s surgery 28th edition Pembrolizumab plus chemotherapy in HER2Neu negative advanced CA stomach VS 1.Better overall survival 2.Lesser treatment related deaths 3.Lesser adverse effects Placebo plus chemotherapy in HER2Neu negative advanced CA stomach

30. RADIOTHERAPY EBRT Earlier Painful bony mets Bleeding tumour SBRT Recent - Oligometastatic disease Adjuvant CT + Local SBRT > Adjuvant CT Adv : Decreased field toxicity Xray photon – destroys malignant cells – whole path Newest avenue – Proton therapy – NO EXIT DOSE

31. CONCLUSION Diagnostic advances -Enhanced imaging and Molecular profiling Early diagnosis Personalised treatment Recent advances in management - improved patient outcomes and quality of life Targeted therapies and immunotherapies Improved survival rates Spares healthy tissue Minimally inasive techniques – Lesser post operative complication Faster recovery Diagnostic and Treatment advances – Renewed Hope – patients and Healthcare providers

32. THANK YOU