Pancreatic carcinoma

Pancreatic carcinoma- types/presentation/management

1. CARCINOMA PANCREAS PRESENTED by--- Dr.JYOTINDRA SINGH MBBS,MS (Gen Surgery) , M.Ch ( Cardiac Surgery)

2. SEMINAR PLAN INTRODUCTION ANATOMY SURGICAL ANATOMY PANCREATIC TUMOURS MODE OF PRESENTATION PRE OPERATIVE WORK UP VARIOUS SURGERIES/ SURGICAL VIDEOS RECENT UPDATES VARIOUS STUDIES/TRIALS TAKE HOME MESSAGE

3. INTRODUCTION Carcinoma of the exocrine pancreas accounts for over 90 % of pancreatic tumors and remains an unreduced oncologic challenge. By definition,periampullary cancers arise within 2 cm of the major papilla in the duodenum. Pancreatic adenocarcinoma accounts for 80% tumours Most common GI malignancy after Ca colon Least 5 years survival rate of 3 %. Incidence rate is virtually identical to the mortality rate

4. INTRODUCTION Pancreatic cancer is a biologically aggressive tumor from the onset . Clinically queisent for a long time and hence present in advanced state. Only 20% of pancreatic cancers are operable for cure Only 10% - 15% of pancreatic cancers are alive 12 months after the diagnosis Average life of metastatic pancreatic cancer is 6 months

5. ANATOMY AND RELATION OF PANCREAS Pancreas is a long retroperitoneal organ 15 to 20 cm in length. Weighs about 80 gms ,lies against L 1 & L 2 Vertebra. It is arbitarily divided into HEAD,NECK BODY & TAIL Head lies within the concavity of duodenum against second lumbar vertebra and body overlies the first lumbar vertebra

6. Cuddles L Kidney Tickles Spleen Cradles Aorta Opposes IVC Dallies with R Renal Pedicle Hugs the duodenum Wraps the SMV Hides behind peritoneum Durman

7. BLOOD SUPPLY PANCREATIC BRANCHES OF SPLENIC ARTERY SUPERIOR PANCREATICODUODENAL ARTERY INFERIOR PANCREATICODUODENAL ARTERY VENOUS DRAINAGE IS INTO SPLENIC VEIN ,SUPERIOR MESENTERIC & PORTAL VEIN

8. VENOUS DRAINAGE

9. PANCREATIC DUCT Main duct of Pancreas ( DUCT OF WIRSUNG )- begins in tail of pancreas and runs on the posterior surface of the body and head of pancreas. HERRING BONE PATTERN DIAMETER OF PANCREATIC DUCT TAIL - 1 to 2 mm BODY - 2 to 3 mm HEAD - 3 to 4 mm Upto 5-6 mm of dilatation in a 70 yr old person is considered normal. Joins the bile duct in the wall of second part of duodenum to form hepatopancreatic ampulla ( of Vater ) DUCT OF SANTORINI- begins in lower part of the head and opens in to duodenum at minor duodenal papilla ( 6-8 cm from

10. Duct of Wirsung Duct of Wirsung

11. Duct of Wirsung &Duct of Santorini

12. Incidence

13. INCIDENCE Annual incidence 10 new cases per 100000 population Lowest incidence – India and Middle East Incidence increases steadily with age – with 80 % over 6 th decade of life Male: Female ratio – 2:1 Pre and post menopausal women ratio is 2: 1

14. ETIOLOGY & RISK FACTORS HEREDITY - CANCER FAMILY SYNDROMES CIGARETTE SMOKING DIET – high intake of animal fat or meat. OCCUPATIONAL EXPOSURE TO RADIATIONS GASTRIC SURGERIES DIABETES MELLITUS/PERNICIOUS ANAEMIA/ CHRONIC PANCREATITIS

15. Etiology – hereditary factors Most of the pancreatic cancers are sporadic 7.8% of pancreatic cancer patients give a positive family history Hereditary syndromes HNPCC PZ syndrome Ataxia Telangiectasia Hereditary Pancreatitis Familial Atypical Mole Melanoma syndrome FAP

16. Etiology – Diabetes – Is it a cause or effect Several studies have shown an increased incidence of pancreatic cancer in diabetics Diabetes is considered as an early symptom of pancreatic cancer rather than being a cause The diabetes of Pancreatic cancer is due to islet cell dysfunction (Islet Amyloid polypeptide) and not due to the destruction of the gland

17. Etiology – Chronic Pancreatitis- Is it premalignant The incidence of pancreatic cancer in various entities of chronic Pancreatitis are as follows Hereditary Pancreatitis 25% Tropical Pancreatitis 10% Alcoholic Pancreatitis 5%

18. Oncogenes in pancreatic cancer K ras P 53 P 16 DPC 4

19. The tumours of the pancreas can be - A. Non-Endocrine neoplasms B. Endocrine neoplasms TUMOURS OF THE PANCREAS

20. ENDOCRINE NEOPLASMS : These are less common than non-endocrine tumours and generally benign and sometimes multiple. They includes:  Insulinoma  Glucogonomas  Others: - Gastrinomas - Somatostatatinomas - Vipomas ( Vasoactive Intestinal Polypeptide) common

21. PATHOLOGICAL ( WHO ) CLASSIFICATION PRIMARY ( 93% ) METASTATIC ( 7 % ) A ) DUCT CELL ORIGIN – 90% 1. DUCT CELL ADENOCARCINOMA – 75 % 2. MUCINOUS CARCINOMA 3. CYSTADENOCARCINOMA B ) ACINAR CELL ORIGIN – 1% 1. ACINAR CELL CARCINOMA 2. CYSTADENOCARCINOMA ( Acinar cell )

22. PATHOLOGICAL ( WHO ) CLASSIFICATION Uncertain Histogenesis ( 9% ) 1. PANCREATOBLASTOMA 2. PAPILLARY AND CYSTIC NEOPLASM 3. MIXED TUMOURS CONNECTIVE TISSUE ORIGIN ( 1 % ) 1. MALIGNANT FIBROUS HISTOCYTOMA 2. OSTEOGENIC SARCOMA 3. LEIOMYOSARCOMA 4. HEMANGIO PERICYTOMA

23. C arcinoma - P ancreas A , A cross-section through the head of the pancreas and adjacent common bile duct showing both an ill-defined mass in the pancreatic substance ( arrowheads ) and the green discoloration of the duct resulting from total obstruction of bile flow . B , Poorly formed glands are present in densely fibrotic stroma within the pancreatic substance; there are some inflammatory cells

24. HISTOPATH

25. Case

26. Case -1

27. CLINICAL MANIFESTATIONS It is unfortunate that malignant pancreatic cancers are asymptomatic until local or systemic complication develop. 1. Obstruction to bile duct – Jaundice and pruritus 2. Obstruction to duodenum /stomach- Gastric outlet obstruction 3. Ulceration- Gastro intestinal haemorrhage 4. Infiltration of peripancreatic nerve roots produce pain The onset of symptoms are insidious and progressive Abdominal pain is usually post prandial and in epigastrium Pain in upper back denotes retroperitoneal extension

28. Pancreatic Tumors in the Head Tumors in the head may compress biliary ducts or pancreatic ducts

29. SYMPTOMS AND SIGNS CARCINOMA HEAD OF PANCREAS 1. WEIGHT LOSS – AVERAGING ABOUT 40% 2. OBSTRUCTIVE JAUNDICE- 3. DEEP SEATED ABDOMINAL PAIN 4. NON TENDER PALPABLE GALL BLADDER 5. CHOLANGITIS OCCURS IN 10 % OF PATIENTS

30. PANCREATIC TUMOURS IN TAIL

31. CARCI NOMA OF BODY AND TAIL WEIGHT LOSS DEEP SEATED PAIN JAUNDICE- < 10 % OF PATIENT SUDDEN ONSET OF DIABETES MELLITUS-25% OF PATIENT MIGRATORY THROMBOPHLEBITIS- OCCURS IN ABOUT 10% PATIENT

32. SYMPTOMS AND SIGNS CARCINOMA OF AMPULLA OF VATER 1. Pain occurs less frequently – usually its colicky 2. Jaundice is often intermittent 3. Chills and fever – due to associated cholangitis

33. Periampullary carcinoma Any tumor within 2 cm from the duodenal papilla is defined as periampullary cancer . Ca terminal PD Distal CBD Ampullary tumor Duodenal tumor

34. Periampullary carcinoma The individual components of peri ampullary tumors differ in their prognosis Duodenal carcinoma Ampullary carcinoma CBD growth Pancreatic ca

35. Site Pancreatic head-2/3 rd Remaining part 1/3 rd

36. Clinical presentation Mid epigastric pain radiating to back Weight loss Fatigue Anorexia Symptoms are vague and hence the delayed presentation

37. Clinical presentation Painless progressive jaundice 50-60% Pruritus Staetorrhea Malabsorption New onset of Diabetes in older patients

38. Clinical presentation Jaundice is a late presentation in uncinate process growth Severe back pain indicate irresectablity and an omnious sign

39. Physical findings Physical findings are rare in pancreatic cancers and their presence usually indicate advanced stage Resectablity is better when patient presents with the classical painless progressive jaundice

40. Physical findings Palpable GB (Courvoisier’s law) Hepatomegaly Icterus Scratch marks Ascites Mass Virchow’s node Pelvic deposit Trousseau’s sign

41. Courvoisier Law

42. Assessment Confirm the diagnosis Stage the disease Assess the operability General assessment for surgery

43. Have A Great Day…

44. Investigation CBC LFT RFT Coagulation profile CXR ECG Echo

45. USG Cheap Level of obstruction Cause of obstruction Liver metastasis Ascites

46. USG Operator dependent Miss small metastasis Cannot assess operability

47. CT “Pancreatic protocol CT” is the gold standard of investigation to stage the disease and assess the operability Triple phase CT Closer cuts Water used as an intraluminal contrast Helical or multislice

48. CT Focal or diffuse mass lesion which is hypo dense (low attenuation) and hypo vascular (poor contrast enhancement) Dilated MPD and CBD

49. Pancreas

50. “ Operability is assessed in the office of the surgeon and not in the Operating room”

51. CT Advantages Available easily Surgeons are familiar with CT Excellent in giving details of operability Disadvantages May miss liver mets less than 1 cm Miss peritoneal mets Radiation

52. MRI Advantages No radiation Avoids contrast Single investigation that gives all the information needed Disadvantages Cost & availability Surgeons are unfamiliar

53. MRI As it stand today CT is as good as MRI Probably in the future, MRI is likely to be used more frequently and may replace CT

54. Role of Biopsy N ot mandatory

55. Role of Biopsy Tissue diagnosis is indicated in cases which are found inoperable by imaging Biopsy is indicated when Neoadjuvant chemotherapy is planned

56. Why not a biopsy May upstage the disease Complications of biopsy Has a very low negative predictive value

57. What biopsy Ideally it should be done under EUS guidance Targeted No tumor seeding No complications like fistula

58. ERCP Double duct sign Not routinely done in pancreatic Cancer Preop biliary drainage Atypical lower CBD obstruction

59. PET It is useful in differentiating pancreatic cancer from chronic Pancreatitis Extra pancreatic disease

60. EUS Ideal method to evaluate lower CBD obstruction Guided FNAC Vascular invasion EUS+FNAC= sensitivity of 90% and specificity of 95%

61. Angiography No longer used

62. Barium studies – only historical Pad sign – widening of C loop Reverse 3 sign or Frostberg sign

63. Tumor markers CA 19-9 CEA CA 125 CA 50 SPAN-1 DUPAN-2

64. Staging TX primary tumor cannot be assessed T0 no evidence of primary tumor T1 confined to pancreas T1a less than 2 cm T1b more than 2 cm T 2 tumor extend to involve the bile duct, duodenum and peripancreatic tissue T3 involvement of stomach, spleen, colon, vessels

65. Staging NX nodes cannot be assessed N0 no evidence of nodes N1 regional nodes present MX cannot be assessed M0 no metastasis M1 distant metastasis

66. Stage grouping Stage I T1 N0 M0 T2 N0 M0 Stage II T3 N0 M0 Stage III Any T N1 M0 Stage IV Any T Any N M1

67. Prognosis Tumor size Node positivity Type of resection (R0 or R1)

68. Operability Ca head 20% Ca body&tail 3% Ampullary 80%

69. Preop preparation Vitamin K Hydration Correction of electrolytes Preop nutrition

70. PANCREATIC SURGERIES WHIPPLES OPERATION – OPEN / LAPROSCOPIC/ ROBOTIC PYLORUS PRESERVING PANCREATICODUODENECTOMY DUODENUM PRESERVING RESECTION OF HEAD OF PANCREAS SUBTOTAL PANCREATECTOMY/TOTAL PANCREATECTOMY ENUCLEATION LAPROSCOPIC STAGING LAPROSCOPIC PALLIATIVE BYPASS PAIN –PALLIATIVE SURGERIES PANCREATIC TRANSPLANTATION ROBOTIC SURGERIES

71. Pancreaticoduodenectomy Pancreaticoduodenectomy offers the surgeon the only chance to cure a patient with carcinoma of the head of the pancreas and periampullary region

72. “ Pancreaticoduodenecomy is the Cadillac of operations” but “It is not a Cadillac that he ( surgeon) is driving but a formula 1 Ferrari”

73. Attitude of the surgeon towards pancreatic cancer Nihilistic Activist Realist

74. Sir Allen O Whipple

75. Pancreaticoduodenectomy Walter Kausch was the first to successfully perform pancreaticoduodenectomy in Berlin 1912 Allen Whipple popularized the operation in US in 1935 Now this operation is called Kausch -Whipple procedure

76. Pancreaticoduodenectomy This operation suffered a very bad reputation due to the operative mortality of over 25% and morbidity of over 50% Some authorities have even suggested that, this operation be abandoned

77. Pancreaticoduodenectomy – consecutive series without mortality J Howard-41 cases 1968 J Cameron 145 cases 1993 Aranha 152 cases 2003 Michael Trede - 118 cases 1990

78. OPERATIVE STEPS Incision- transverse subcostal / midline Exploration/mobilization- kocherization Cholecystectomy /dissection of hepatoduodenal ligament Mobilization of pancreatic neck Partial gastrectomy Division of pancreas Dissection of retropancreatic vessels Division of jejunum Reconstruction

79. Whipple – 6 well defined operative steps 1. Cattle Brasch maneuver 2. Extended Kocherization 3. Portal Dissection, division of Bile duct 4. Division of Stomach 5. Division of Jejunum 6. Pancreatic Neck transection

80. Reconstruction after Classical Whipple’s operation Hepaticojejunostomy Gastrojejunostomy Pancreaticojejunostomy

81. PANCREATICODUODENECYTOMY- PYLORUS PRESERVATIION Incision- transverse subcostal / midline Exploration/mobilization- kocherization Cholecystectomy /division of the bile duct Exposure of superior mesenteric vein Division of duodenum Division of gastroduodenal artery Division of pancreatic neck Dissection of uncinate process Resected specimen- gallbladder,distal bile duct,2 nd 3 rd &4 th part of duodenum,proximal jejunum and head ,neck & uncinate portion of pancreas Reconstruction

82. Pylorus preserving Pancreaticoduodenectomy

83. Reconstruction after PPPD

84. Duodenum- preserving resection of the head of pancreas Incision- transverse subcostal / midline Exploration/mobilization- kocherization Exposure of the pancreas Dissection of the neck of pancreas Resection along the CBD Pancreatic remnant Reconstruction Bile duct anastomosis Stenosis of the pancreatic duct

85. TOTAL PANCREATECTOMY This involves the en bloc resection of The whole of pancreas The spleen Distal half of stomach Duodenum Proximal 10 cm of jejunum Gall bladder Cystic and common bile duct

86. TOTAL PANCREATECTOMY Incision- Transverse muscle- cuting incision Exploration/mobilization- kocherization Mobilization of duodenum/head of pancreas Exposure of body and tail of pancreas Dissection of the vessels- hepatic artery is traced Mobilization of spleen and pancreas Limited gastrectomy /pylorus preserving resection Reconstruction – choledochojejunostomy /bowel anastomosis

87. Total Pancreatectomy Reconstruction

88. REGIONAL PANCREATECTOMY TYPE O – TOTAL PANCREATECTOMY TYPE I -- RESECTION OF PORTAL VEIN SEGMENT TYPE II a – Type I plus resection of proximal SMA TYPE II b– Type I plus resection of celiac axis/hepatic artery TYPE II c-- Type I plus resection of celiac axis & SMA

89. PANCREATIC ENDOCRINE DISEASE Principles- whether tumour functioning or non-functioning tumour benign or malignant sporadic occurrence or part of MEN-I Operative steps IOUS- localization of islet cell tumours delineation of proximity of tumour to pancreatic duct demonstration of multiple tumours as part of MEN-I ENUCLEATION- CUSA DISTAL PANCRETECTOMY

90. PANCREATIC CANCER- LAPROSCOPIC STAGING 7.5 Mhz linear array transducer Port- infraumbilical and right flank Search for serosal deposit Lesions on liver sampled/GB visualised Transducer placed on porta hepatis Look for dilataion of pancreatic duct Position of tumour relative to pancreatic duct/portal vein Lymphnodes more than 10 mm -significant

91. PANCREATIC TRANSPLANTATION Suitable donors between 20 and 50 yrs Pancreatic blood flow to be maintained- warm ischemia Gland should be perfused with a cold preservation fluid- hypertonic citrate solution Pancreas removed avoiding damage to the gland– injection of collagenase enzyme into the pancreatic duct under pressure. Pancreas transported to processing centre-within four hours- cold ischemia

92. RECENT UPDATES/CHANGING APPROACH Preop biliary drainage Preop imaging, CT vs. MR vs. EUS Role of biopsy Diagnostic laparoscopy PJ vs. PG Classical Whipple vs. PPPD Vascular resections Extended lymphadenectomy Drainage

93. Controversies Role of octreotide Order of reconstruction Adjuvant therapy Palliative resections Palliative bypass

94. Preop biliary drainage For Reduce the mortality and morbidity of surgery Improves the liver function Reduces the bleeding Improves the nutrition Buys time

95. Preop biliary drainage Against Does not reduce the mortality and morbidity More infectious complications It takes 6 weeks for the improvement of hepatic microsomal functions Makes the duct small and fibrotic – adds to technical difficulty

96. Preop biliary drainage - consensus Indicated Cholangitis Impending renal failure Surgery is likely to be delayed Bilirubin of more than 20 mg% Nutritionally very poor Neoadjuvant chemotherapy is planned

97. Preop biliary drainage - consensus Routine preop biliary drainage is not recommended and there is no evidence to support it

98. Diagnostic laparoscopy 30% of patients found operable by imaging are found to have small liver mets or peritoneal mets , on diagnostic laparoscopy Warshaw et al

99. Diagnostic laparoscopy With the advent of high quality CT, Helical and Multislice, occult peritoneal and liver metastasis are documented in only 10% in some series

100. PJ vs. PG Merits of PG Stomach is in proximity to pancreatic stump Better vascularity Acid in stomach inactivates enzymes Absence of enterokinase Even if leak occurs the enzymes are not activated and hence fatal bleeding do not occur

101. PJ vs. PG Two randomized controlled trials fail to demonstrate superiority of one method over the other Dilated duct, texture of pancreas and surgeon’s experience are more important than the viscera used for drainage

102. Classical Vs PPPD PPPD is oncologically as radical as classical whipple except for tumors encroaching on the D1 and pylorus RCTs have failed to show any significant benefit of PPPD over classical whipple

103. Vascular involvement Resection of SMV is accepted provide it enables to perform R0 resections Involvement of SMA is a contraindication for resection

104. Extended lymphadenectomy Studies have shown that extended lymphadenectomies can be done with acceptable morbidity Extended lymphadenectomy do not improve the survival

105. Octreotide There have been totally six RCT across the Atlantic, three from Europe ( Buchler et al, Beger et al , Pedrazolli et al) and three from US ( Yeo et al, Sarr et al and Lowy et al) The European trials favor use of octreotide and the American trials do not favor Recently published meta analysis of these trials have shown a benefit f octreotide in reducing the complications

106. Adjuvant therapy Chemotherapy Radiotherapy Chemo radiotherapy

107. Adjuvant therapy The ESPAC trial has shown that the only factor that positively affect the long term survival is administration of adjuvant chemotherapy Ideally all patients undergoing surgery for cancer pancreas should be given adjuvant chemotherapy

108. Palliation Jaundice (pruritus) Duodenal obstruction Pain Bleeding

109. Palliative resections – Is it acceptable Palliative resections and palliative bypass has the same survival Hence palliative resections are not accepted

110. Palliative resections The series from John Hopkins has shown survival benefits in R1 and few cases of R2 Whipple

111. Palliative resections The consensus is that one should not willfully perform a palliative resection, and the aim of the surgeon should always be a R0 resection

112. Palliative bypass Operative palliation is not the standard of care for a patient with inoperable Ca pancreas with obstructive jaundice Endoscopic palliation is the treatment of choice

113. Palliative bypass A selected group of patients with good performance status Patients who are found to be inoperable on the table Endoscopy facilities not available or not possible for technical reasons

114. Palliative bypass Options of by-pass Choledochojejunostomy ( Loop or Roux en Y) Cholecystojejunostomy Hepaticojejunostomy

115. Palliative bypass-prophylactic GJ The current recommendation is to perform a prophylactic GJ along with the biliary bypass even if there is no gastric outlet obstruction

116. Laparoscopy in palliation Depending on the expertise of the surgeon, procedures can be done with laparoscopy

117. Palliation of pain Neurolysis ( 20 ml of absolute alcohol injected on either side of the celiac axis to destroy the celiac ganglia) At laparotomy CT guided EUS guided Thoracoscopic splanchnectomy

118. ROBOTIC SURGERIES

119. TAKE HOME MESSAGE Survival rate of patients after the establishment of diagnosis is very dismal. Surgical resection if possible ,is the only curative treatment but it can play a role only in very small percentage of cases Post surgery five year survival rate is least in pancreatic malignancy.tive Newer approaches are less radical and more effective Concept of regional pancreatectomy has increased poet op survival period Survival can be further increased by- early detection - avidance of surgery in presence of metastasis - operative technique with avoidance of local spillage - avoiding preoperative blood transfusion.

120. REFERENCES BAILEY & LOVE’S- SHORT PRACTISE OF SURGERY SABISTON TEXTBOOK OF SURGERY MASTERY OF SURGERY by Fischer OXFORD TEXTBOOKOF SURGERY MAINGOTS ABDOMINAL OPERATION MAYO CLINIC GI SURGERY CANCER PRINCIPLES- De Vita SURGERY BY CORSON RECENT ADVANCES- WOLTERS KLUWER RECENT ADVANCES- RSG

121. Questions?

122. Thank You