HPB & UGI Cancer. Mr Brett Knowles Hepatopancreaticobiliary, Trauma, Emergency and General Surgeon RMH, SVH, Peter MacCallum

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1 HPB & UGI Cancer Mr Brett Knowles Hepatopancreaticobiliary, Trauma, Emergency and General Surgeon RMH, SVH, Peter MacCallum

2 Overview Presentation Assessment Diagnosis Staging Treatment Curative Palliaitive Pancreatic Oesophageal Primary liver HCC

3 Pancreatic Cancer

4 Epidemiology - PDA 2.2% of all new cancers 9 th most common 10 cases per Almost identical to mortality rate of 9.9 cases per % of all cancer deaths 5 th most common cause of cancer death Overall survival is poor 5y OS increased from 3 to 5.2% last 20 years

5 Surgery best chance survival Overall 5y survival 5% and 15 to 20% in best surgical series At present, surgery remains necessary, albeit not sufficient, to obtain the long-term survival that pancreatic cancer patients and physicians are looking for

6 Risk factors Increasing age Smoking Male (probably reflects smoking) Obesity BMI > 35 RR >2x Diabetes early and late Alcohol heavy consumption >6 units per day Gentic polymorphisms non O blood grps, HNF1A Family History

7 Familial Pancreatic Cancer Cluster: No inherited genetic syndrome FHx seen in 5 to 10% those with Pancreatic cancer BRCA 1 & 2 Germline: PLAB2 (BRAC2 related) familial breast cancer BMI, smoking, other Risk tied to number of first degree relatives 2 = 4.6 x RR HNPCC (Lynch) & FAP Peutz Jeghers Syndrome Hereditary Pancreatitis 40% by 70y Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) Screening high risk patients????

8 Intra-ductal Papillary Neoplasm (IPMN) Main duct, side or mixed branch M=F Can present with recurrent pancreatitis or symptoms chronic pancreatitis

9 Radiology MD = dilatation of duct >10mm High risk malignancy SB low to moderate risk malignancy Often in uncinate > 3cm, PD > 6mm, mural nodules Requires post resection surveillance

10 At ERCP Mucous bulging at ampulla

11 IPMN and extra-pancreatic malignancies Increased risk Gastric cancer Colon cancer Cholangiocarcinoma Lymphoma Recommend gastroscopy and colonoscopy

12 Symptoms: Pancreatic Cancer Early Upper abdominal pain Loss of appetite Weight loss Nausea and vomiting Altered Bowel habbit Jaundice Less common New onset diabetes Severe back pain Unexplained thrombophlebitis Pancreatitis PNET functional tumours

13 Clinical Jaundice Painless Symptoms Palpable gallbaldder Ascites Supraclavicular nodes

14 Radiology CT MRI/MRCP EUS PET

15 Radiology: CT A. Pancreatic adenoca B. AIP normal duct C. Neuroendocrine D. Melanoma metastases

16 MRI/MRCP MRI pancreas little extra information to CT MRCP much better delineation of duct Double duct sign

17 PET No clearly defined role in PDA Gold std in staging P-NET Ga-Tate FDG 68 GaTate PET/CT 2-3mm hepaticmet Pancreatic primary 68 Gaoctreotate Contrast enhanced CT

18 ERCP and EUS ERCP Diagnostic use limited in era MRCP and EUS Major role in relief of biliary obstruction EUS Diagnostic Biopsy if required

19 Work up of Pancreatic Mass Wide range of clinical entities Broadly classify as solid and cystic

20 Practical Majority of solid lesions are PDA Requires prompt assessment At same time rare neoplasm not PDA Neuroendocrine Metastases Identify neoplasm not requiring surgery Lymphoma Benign Autoimmune pancreatitis

21 Assessment Determine risk of malignancy Stage disease Local vs advanced vs metastatic Resectable Determine patients surgical risk Determine need for multimodality treatment in an MDT setting

22 Surgery for Pancreatic cancer Whipple s Pancreaticoduodenectomy Distal pancreatectomy Spleen? Total pancreatectomy

23 What does this mean?

24 Palliation of Pancreatic Cancer Treatment Intent for majority Surgery/Endoscopic Gastric outlet obstruction Obstructive jaundice Pain? Depression Chemotherapy Radiotherapy Pain Community Palliative care

25 Role Adjuvant therapies Radiotherapy 5 FU 5 FU & Gemcitabine Chemotherapy Gemcitabine FOLFOXFIRI Abraxane

26 Radiotherapy Local advanced Only benefits those who don t develop mets Delay till after systemic Rx? Palliates pain In general adds little additional survival to chemotherapy alone (9 to 13 months) Stereotactic body radiotherapy Issues with toxicity due to proximity of stomach and duodenum

27 Summary of treatment Surgery still gold standard R0 resection Resectable Adjuvant CTx Borderline CTx Resectable Biological Medical Locally advanced Ctx RTx Metastatic = CTx

28 Surgery

29 Oesophageal Cancer GOORD and Barrett s oesophagus Smoking and alcohol 1:3 undergo surgery Roles for chemotherapy and radiotherapy

30 Malignancy Oesophageal adenocarcinoma (AC) and Squamous cell carcinoma (SCC) Rapidly progressive dysphagia, initially for solids and later for liquids Chest pain, odynophagia, anemia, anorexia, and significant weight loss.

31 Dyspahgia is not normal

32 Barrett s Now early treatment modalities Halo EMR Key is finding and surveillance 10 to 20y to develop Scope chronic reflux 10y For Barrett s with dysplasia

33 Evaluation Prompt History Investigations Endoscopy Swallow radiology Motility studies

34 Type of food and temporal progression Do you have problem swallowing solids, liquids, or both How long? and have your symptoms progressed, remained stable, or are they intermittent? Could you point to where you feel food is getting stuck Liquids, and or solids from onset, suggests a motility disorder Solids progressing to liquids suggests stricture Rapid progression = malignancy? Intermittent most often related to a web or ring

35 Staging Patient Fitness No mets CT Role neoadjuvant therapy Curative = Surgery Palliate Dysphagia Bleeding QAL Surgery, Radiotherapy, Chemotherapy

36 Oesophageal Cancer

37 Hepatoma

38 Intro Hepatocellular carcinoma (HCC): malignant tumors of liver parenchymal cells Aggressive Often occurs in setting of chronic liver disease Primary liver cancer is the fifth most common cancer in the world and the third most common cause of cancer mortality (2 nd in Men) Median survival following diagnosis is approx 6 to 20 months

39 HCC 39

40 HCC 40

41 Obesity

42 Risk Factors HBV Even without cirrhosis (70 t 90% will have cirrhosis) Viral load HCV Haemaochromatotis Protection Statin use Chinese population study 328,946 person-years of follow-up And maybe coffee! Cirrhosis any cause

43 Treatment Potentially curative Liver transplantation Resection Ablation Thermal (RFA/MWA) Chemical (Ethanol) Palliative Chemoembolisation (TACE) Radiotherapy External Beam Embolisation Sorafenib

44 BCLC Staging the treatment HCC ; European Organisation for Research and Treatment of Cancer. J. Hepatol. 56, (2012). 44

45 BCLC Staging the treatment HCC ; European Organisation for Research and Treatment of Cancer. J. Hepatol. 56, (2012). 45

46 BCLC Staging the treatment HCC ; European Organisation for Research and Treatment of Cancer. J. Hepatol. 56, (2012). 46

47 BCLC Staging the treatment HCC ; European Organisation for Research and Treatment of Cancer. J. Hepatol. 56, (2012). 47

48 Problems Limitied treatment options for B & C patients These make up majority or patients presenting with HCC The Milan criteria for liver transplantation for HCC are not included explicitly even though they are widely accepted Value of resection for some "early stage" (with a single tumor size >2 cm or multiple nodules "intermediate stage" (patients who have multi-nodular tumors but a good performance status)

49 HCC Surgery Transplant Milan Criteria 1 < 5cm 3 < 3cm No PVT No Metastases Resection Open Laparoscopic

50 Surgery Resection EAST Anatomically based Now increasing use of living related donor transplantation and laparoscopic resection WEST Traditionally transplant programmes Increasing resection Younger well compensated cirrhosis due to HBV Over 60y, co-morbidites and alcoholic and HCV > HBV

51 Contraindications to Resection Tumour Biology Size? 5cm? 10 cm? PV invasion? Hepatic vein invasion? Perforation? Nodal metastases? Liver disease Inadequate hepatic reserve

52 Ruptured HCC Poor outcome not inevitable Low but definite long tern survival rate after resection 1. Control bleeding 1. Embolism 2. Formal staging 3. Subsequent attempt at resection

53 Pre op assessment of hepatic reserve Child Pugh score Volume Functional testing IGC Pragmatic CPA +/- PHT CPB without ASCITES

54 Ablation techniques Chemical Ethanol injection Thermal Cyro RFA & MWA Novel Laser HFU

55 Thermal FREEZE Cryotherapy Freeze thaw cycle Coolant then Helium gas to thaw Liver Fracture and cyroshock HEAT Radiofrequency ablation (RFA) Microwave ablation (MWA) >60 denaturing and cell necrosis Homogenous tissue heating Conductive Zone

56 Radiofrequency Ablation High-frequency (460 khz) alternating current flows from electrical probe through tissue to ground Agitates ions cause frictional heat conducted to tissues Can perform percutaneously, laparoscopically or at open surgery General Anaesthetic as cause severe pain Probe insertion Extension of prongs RF current application

57 Single Needle vs. 3.5 cm LeVeen Needle

58 RFA Currently most used ablative modality for liver tumours Ohms Law: I (current) = V (voltage)/r (resistance) R of liver changes as liver coagulates and desiccates Current finds path of least resistance Heat Sink as blood vessels carry current away >10 x lower R Charring Smaller heterogeneous ablation zone

59 Studies RFA and HCC Large clinical series from Europe, Asia and United States 5 year post RFA survival rates between 33% and 55% Buscarini et al Eur Radiol 2001 Lencioni et al Radiology 2005 Raut et al Ann Surg Oncol 2005 Taeishi et al Cancer 2005

60 RFA vs surgical resection HCC PRCT Chen et al Ann Surg (3): 321 Endemic HBV 112 patients Single HCC less 5 cm diameter 65 resection vs 47 RFA No significant difference in local recurrence, overall survival or disease-free survival between the 2 groups Mortality 1% vs 0% Morbidity 56% vs 4% (P<0.05) LOS greater for surgery ( vs 9 + 3, P<0.05)

61 Conclusions RFA and HCC Primary therapy for unresectable HCC less than 3 cm in size Potential alternative to surgery for resectable small HCC

62 Microwave Ablation Microwave refers to the region of the EMS between 900 and 2450 MHz Microwaves cause water molecules to agitate 2 billion times a second This produces friction and heat thereby causing cell death by coagulation necrosis No current through patient so no grounding pad MW 1-2 cm

63 Laparoscopic MWA

64 Trans arterial chemoembolisation TACE 64

65 TACE Bland Chemotherapy 2 Meta analysis failed to show significant difference TAE and TACE Lipiodol Embolism Gelatin PVA Beads TACE shown in 2 RCT improve survival in unresectable HCC but not in 3 others

66 Contraindications Thrombus in the main portal vein and portal vein obstruction Encephalopathy Biliary obstruction Child-Pugh C cirrhosis Relative Tumor burden involving >50 percent of the liver Cardiac or renal insufficiency Ascites, recent variceal bleed, or significant thrombocytopenia Transjugular intrahepatic portosystemic shunt (TIPS)

67 TACE selection The best candidates for TACE are patients with unresectable lesions: Large (>10cm) Multifocal Without vascular invasion Without extrahepatic spread Preserved liver function - Child-Pugh A or B

68 Radiation Therapy External Beam Stereotactic Radio embolism Sirtex spheres (Yi 90 glass spheres 131 iodine Lipiodol HCC is a radiosensitive tumor, it is located in an extremely radiosensitive organ

69 Systemic Molecular = Sorafenib 2007 SHARP trial: median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo Llovet NELM 2008 Cytotoxic: Not used often as: HCC relatively refractory Survival often dependent on liver function