Determining resectability in pancreatic cancer

Determining resectability in pancreatic cancer

1. DETERMINING RESECTABILITY IN PANCREATIC CANCER Moderator : Dr. B. Srihari rao M.S Dr. C. Srikanth Reddy M.S Dr. K. Keerthinmayee M.S Presenter: Dr. Harish Y S

2. Discussed by INTRODUCTION CLASSIFICATION OF TUMORS STAGING OF TUMORS ANATOMY OF PANCREAS National Comprehensive Cancer Network ( NCCN) GUIDELINES INCREASING RESECTABILITY RATES VENOUS RESECTION ARTERIAL RESECTION . MANAGEMENT

3. INTRODUCTION It is the 13th most common cancer worldwide. 5 th MC cause of cancer-related mortality. I ncidence rate is 9.7 per 100,000. I ts peak incidence between the 7 & 8 decades and It is rare < 40yrs. M ale to female ratio is 1:1 Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001;37 Suppl 8:S4-66

4. INTRODUCTION It has an overall survival of 0.4 % to 4 %. These patients presents late, At the time of diagnosis < 20% of patients are surgically resectable disease Of the inoperable ones, 1/3 rd. with distant metastases and Remaining 1/3 rd. with locally advanced disease. Defining resectability is therefore one of the most important and crucial aspects in the management of pancreatic cancer.

5. WHO Classification of pancreatic exocrine tumors Benign tumors: Serous cystadenoma Mucinous cystadenoma Intraductal papillary-mucinous adenoma Mature teratoma Borderline (uncertain malignant potential) Solid- pseudopapillary neoplasm Most common

6. WHO Classification of pancreatic exocrine tumors Malignant tumors: Ductal adenocarcinoma Mucinous noncystic carcinoma Signet ring cell carcinoma Adenosquamous carcinoma Undifferentiated (anaplastic) carcinoma Serous cystadenocarcinoma Mucinous cystadenocarcinoma intraductal papillary-mucinous carcinoma Acinar cell carcinoma Pancreatoblastoma Solid- pseudopapillary carcinoma

7. TNM STAGING:

8. The American joint committee on cancer stage

9. Arterial supply of pancreas

10. Venous drainage of pancreas

11. Lymphatic drainage of pancreas

12. Historically pancreatic tumours have been classified as either resectable or unresectable . It is primarily the relationship of the pancreatic cancer to the vessels that defines resectability. Over the last two decades the terms “locally advanced” and “borderline resectable ” pancreatic cancer have come in to use.

13. LOCALLY ADVANCED PANCREATIC CANCER Locally advanced pancreatic cancer is described as Tumor invaded locally adjacent structures such as major blood vessels, lymph nodes, bowel or the bile duct, without evidence of distant metastatic disease . Involvement of para -aortic LN considered as metastasis and sugically contrindicated . Locally advanced pancreatic cancer may or may not be resectable and would include T3 and T4, whereas T1 and T2 are considered resectable tumours .

14. BORDERLINE RESECTABLE PANCREATIC CANCER It is defined by two groups MD Anderson Cancer Center ( MDACC) American HepatoPancreatoBiliary Association (AHPBA )/ Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT ) MDACC group describes any venous involvement as resectable disease and only occlusion of the SMV or PV (with the possibility of reconstruction) as borderline. Cooper AB, Tzeng CW, Katz MH. Treatment of borderline resectable pancreatic cancer. Current treatment options in oncology. 2013;14(3):293-310.

15. National Comprehensive Cancer Network (NCCN) Guidelines for pancreatic cancer treatment. Pancreatic cancers classified in to Resectable Borderline resectable and Unresectable . Resectable Arterial : Clear fat planes around the coeliac axis (CA), SMA and HA. Venous : The SMV or PV abutment but no distortion of the vessels.

16. Borderline Resectable Arterial : Pancreatic head / uncinate process: Solid tumor contact with CHA without extension to celiac axis or hepatic artery bifurcation. Solid tumor contact with the SMA of ≤180° Presence of variant arterial anatomy (ex: accessory right hepatic artery, replaced right hepatic artery, replaced CHA) and the presence and degree of tumor contact should be noted if present as it may affect surgical planning .

17. Borderline Resectable Pancreatic body/tail: Solid tumor contact with the CA of ≤180° Solid tumor contact with the CA of ˃180° without involvement of the aorta and with intact and uninvolved gastroduodenal artery. Venous : Venous involvement of the SMV or PV with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement.

18. Unresectable : Arterial ( Head of Pancreas ) : Greater than 180° encasement of the circumference of the SMA or any CA abutment. Arterial ( Body/Tail of Pancreas ) : SMA or CA encasement >180°. Arterial ( Any Part of the Pancreas ) : Aortic invasion or encasement . Venous : Unreconstructable SMV and/or PV . Nodal Status : Metastases to lymph nodes beyond the field of resection should be considered unresectable .

19. Grading system proposed by Lu et al. for predicting vascular invasion by tumor based on the degree of tumor contiguity with a vessel GRADE DESCRIPTION COMMENT Grade 0 No contiguity of tumor with a vessel Vascular invasion in 0% of cases Grade 1 Tumor is encasing <25% of the circumference of a vessel 0% Grade 2 25–50% of the circumference of a vessel 57% Grade 3 50–75% of the circumference of a vessel 88% Grade 4 >75% of the circumference of a vessel or any vessel constriction All cases

20. A fat plane is seen between the tumor and the superior mesenteric artery (SMA) and superior mesenteric vein. No evidence of vascular invasion is seen. The tumor is contiguous with < 90° of the superior mesenteric vein ( Lu grade 1). There is no narrowing or wall irregularity of the SMV MDCT OF PANCREATIC CARCINOMA

21. The tumor is contiguous with 90 °- 180 of the superior mesenteric vein (Lu grade 2). There is no narrowing or wall irregularity of the SMV. The tumor (T) in the head of the pancreas eroding the wall of the superior mesenteric vein (SMV) and penetrating it to form a tumor thrombus

22. Grading system proposed by Loyer et al . for predicting vascular invasion by tumor GRADE DESCRIPTION COMMENT Type A Fat plane separates the tumor and the normal pancreatic parenchyma from adjacent vessels Overall resection rate: 100%. Type B Normal parenchyma separates the tumor from adjacent vessels Overall resection rate: 100%. Type C Tumor is inseparable from adjacent vessels, and the points of contact form a convexity against the vessels Overall resection rate: 89%. Type D The points of contact form a concavity against the vessels or partially encircle the vessels Overall resection rate: 47%. Type E Tumor encircles adjacent vessels, and no fat plane is identified between the tumor and the vessels Overall resection rate: 0%. Type F Tumor occludes the vessels Overall resection rate: 0%.

23. APPROCH TO A PATIENT Clinical suspicion of pancreatic cancer or evidence of dilated pancreatic duct. MDCT angiography Mass in pancreas No mass in pancreas No metastasis Multidisciplanary review LFT EUS Chest imaging Metastasis Biopsy confirmation No metastasis LFT EUS/FNA Chest imaging MRCP/ERCP Metastasis Biopsy confirmation EUS

24. APPROCH TO A PATIENT No metastatic disease on physical examination and imaging No jaundice jaundice Symptoms of cholangitis or fever Short or self expanding metal stents and antibiotic coverage No symptoms of cholangitis Per operative CA-19-9 RESECTABLE BORDERLINE RESECTABLE LOCALLY ADVANCED , UNRESECTABLE

25. RESECTABLE TUMOR Consider staging laparoscopy in high risk patients LAPAROTOMY Surgical resection Adjuvent treatment and surveillance Unresectable tumor Biopsy confirmation, if not performed previously No jaundice Gastrojujunostomy + celiac plexus neurolysis (if pain) Jaundice Self expanding metal stents or biliary bypass + Gastrojujunostomy + celiac plexus neurolysis (if pain)

26. The goals of surgical extirpation of pancreatic carcinoma focus on the achievement of an R0 resection a margin positive specimen is associated with poor long-term survival Achievement of a margin negative dissection must focus on meticulous perivascular dissection of the lesion in resectional procedures, recognition of the need for vascular resection and/or reconstruction

27. Surgical Procedures Tumors of the Body and Tail Distal Pancreatectomy Removal of body & tail of pancreas spleen

28. Surgical Procedures Head of the pancreas: Whipple Procedure Removal of: Distal stomach Duodenum and proximal jejunem Head of pancreas Gallbladder and common bile duct

29. Total pancreatectomy Indicated in tumor with multilocular or large tumors. It is combination of pancreaticoduodenectomy and distal pancreatectomy with local lymphadenectomy. Complications are post operative exocrine and endocrine insufficiency and associated with high mortality rates.

30. If the tumor is found to be unresectable during surgery biopsy confirmation of adenocarcinoma can be done. If a patient with jaundice is found to be unresectable at surgery stenting or biliary bypass can be done

31. BORDERLINE RESECTABLE, NO METASTASIS Planned neoadjuvent therapy Biopsy/ EUS+FNA / staging laparoscopy Biopsy confirmed Imaging: abdomen , chest and pelvis Consider staging laparoscopy Surgical resection Unresectable Cancer not confirmed Repeat biopsy Biopsy confirmed Biopsy not confirmed Planned resection

32. INCREASING RESECTABILITY RATES Survival for pancreatic cancer has not changed in the last 40 years. However, with advancement in surgical technique and improvement in perioperative care. In Specialised centres , postoperative mortality rates of 2–3% have been reported. The increased resectability and improve in long-term survival for patients with pancreatic cancer, extensive surgical procedures have been developed, mainly involving vascular reconstruction techniques.

33. INCREASING RESECTABILITY RATES Birkmeyer et al. first reported aggressive surgery for borderline resectable pancreatic cancer with the first SMV resection and reconstruction in 1951 . In 1973, Fortner first described the regional pancreatectomy . This involved a total pancreatectomy , radical lymph node clearance, combined PV resection (type 1) and/or combined arterial resection and reconstruction (type 2 ).

34. Venous Resection Venous involvement is not considered a contraindication to surgical resection. P ancreatic resection requiring venous reconstruction is technically challenging and may be associated with a higher morbidity. Ravikumar et al . published multicentre retrospective cohort study comparing, PD with venous resection (PDVR ) and surgical bypass for T3 adenocarcinoma of the head of the pancreas. 1.Morbidity was similar between the PDVR and PD groups, 2.Patients requiring blood transfusion being greater in the PDVR group. Ravikumar R, Sabin C, Abu Hilal M, et al. Portal vein resection in borderline resectable pancreatic cancer: a United Kingdom multicenter study. J Am Coll Surg . 2014;218(3):401-11.

35. Venous Resection In 2006, Siriwardana reported a large systematic review of 1646 patients who had undergone portal-SMV resection during pancreatectomy for cancer . concluded that, with the high rate of nodal metastases and the low five-year survival rates, once the PV is involved cure is unlikely even with radical surgery. Several studies have shown that PV resection in patients with pancreatic cancer has comparable survival compared to standard pancreatectomy and It is a safe procedure when performed in specialist HPB Units Siriwardana HP, Siriwardena AK. Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer. Br J Surg. 2006;93(6):662-73

36. Venous Resection Lygidakis et al. compared en bloc splenopancreatic and venous resection versus palliative gastrobiliary bypass and reported two-year survival rates of 81.8% and 0%, respectively. R andomised controlled trial by Doi et al. in 2008 was closed early when interim analysis showed a clear survival benefit for PDVR with chemoradiotherapy compared with chemoradiotherapy with or without a surgical bypass Lygidakis NJ, Singh G, Bardaxoglou E, et al. Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepatogastroenterology . 2004;51(56 ):427-33. Doi R, Imamura M, Hosotani R, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today. 2008;38(11):1021-8.

37. Arterial Resection In 2007, Hirano et al. reported their long-term follow-up for patients undergoing distal pancreatectomy with en bloc CA resection (DP-CAR) They reported 1yr and 5yr survival rates of 71 % and 42%, respectively, and concluded that DP-CAR offers a high resectability rate and may potentially achieve complete local control in selected patients . Hirano S, Kondo S, Hara T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg . 2007;246(1):46-51.

38. Arterial Resection Bachellier et al., in 2011, matched a group of patients undergoing pancreatectomy with arterial resection to conventional pancreatectomy and demonstrated similar three-year survival rates . Bockhorn et al. reported one of the largest series on pancreatectomy with simultaneous arterial resection ( n = 29) and concluded that there was no overall difference in disease-specific survival for patients who underwent arterial reconstruction versus those patients who underwent pancreatectomy alone Bachellier P, Rosso E, Lucescu I, et al. Is the need for an arterial resection a contraindication to pancreatic resection for locally advanced pancreatic adenocarcinoma? A case-matched controlled study. J Surg Oncol . 2011;103(1):75-84. Bockhorn M, Burdelski C, Bogoevski D, et al. Arterial en bloc resection for pancreatic carcinoma . Br J Surg. 2011;98(1):86-92.

39. Arterial Resection Mollberg et al. in 2011, systematic review and meta-analysis . This report included 26 studies, a total of 2609 patients , 366, out of the 2609 patients underwent an arterial resection and reconstruction in conjunction with a pancreatectomy . Results : S ignificantly increased perioperative morbidity and a mortality rate compared with standard pancreatectomy . Significantly poorer survival outcomes at one year (49.1%), three years (8.3 %) and five years (0%) were demonstrated in this study

40. LOCALLY ADVANCED UNRESECTABLE TUMOR Biopsy ,if not previously performed Adenocarcinoma confirmed If jaundice, placement of self expanding metal stents. CHEMOTHERAPY Cancer not confirmed Repeat biopsy Others cancers Treat as appropriate

41. LOCALLY ADVANCED UNRESECTABLE TUMOR FOLFIRINOX or Gemcitabine or Gemcitabine + albumine bound paclitaxel. or Capecitabine + continuous IV 5-FU or Fluropyrimidine + oxaliplatine or Clinical trial preferred. Fluropyrimidine based therapy if previously treated with Gemcitabine based therapy Gemcitabine based therapy if previously treated with Fluropyrimidine based therapy PALLIATIVE AND BEST SUPPORTIVE CARE

42. METASTATIC DISEASE If jaundice, placement of self expanding metal stents . Good performance CHEMOTHERAPY Poor performance Palliative and supportive care.

43. SURVIVAL 5-year survival rate of R0 resection - 24.2% R1 and R2 resection - 4.3% Median survival i n R0 resected patients, the was 28 months with pancreaticoduodenectomy and 26 months with PPPD . R1 resected patients - 15 months R2 resected patients - 9.8 months Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:58694

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