Pancreatic Cancer ( Malignant Obstructive Jaundice )

Case Discussion for Medical Students and Brief Education on Pancreatic Carcinoma.

1. Pancreatic Carcinoma Dr Muhammad Saad Iqbal Resident of Surgery SLMC

2. Case Scenario 52 year old male patient presents with progressive Jaundice , itching, loss of weight. • Gradually progressive jaundice • Recurrent episodes of itching • White stools for last 2 months • Dark yellow urine • Generalized weakness & fatigability- 6 months • Weight loss in last 1 year • Reduced appetite • No fever

3. H/o past illness: • No H/O DM, HT, TB, IHD • No previous surgery(no history of cholelethiasis ). Personal History: • Decreased appetite with pale stools • Normal bladder habits but deep yellowish colour • Smoker – 4 yrs • Non-alcoholic

4. Examination General Physical Examination : – Pulse 88/ min,BP 110/70, RR 16, Temp 98 F – Anemia +, Jaundice ++ – No Lymphadenopathy – Scratch marks Per abdomen: Normal Inspection On palpation: – Soft non-tender – Gall bladder palpable BS audible

5. Routine Investigations • Hgb : 11.7 • Hct : 35 • WBC: 6000 ; • normal differential count • Platelet: 350,000 • Serum Crea : 1.2 mg • Total bil : 20 mg; B1( unconj ): 2 mg B2 ( conj ): 18 mg • Alkaline phosphatase: 990 U/L • CA 19-9: 350 units/ml • Total protein: 6.5 grams

6. • USG-Abdomen : Solid mass in distal CBD, dilated CBD, Intrahepatic Biliary distension and distended GB .

7. CT abdomen e IV contrast: It showed grossly dilated intra and extrahepatic biliary channels With distended gall bladder And possibility of periampullary mass .

8. MR cholangiopancreatography (MRCP), which can be used to look at the pancreatic and bile ducts, is described below in the section on cholangiopancreatography. a) 3D magnetic resonance cholangiopancreatography with maximum intensity projection; (b) coronal T2-weighted image; (c) 2D magnetic resonance cholangiopancreatography: mild dilated bilobar radicles [(b), yellow arrow] with dilated common bile duct [(a) and (c), yellow arrow] with distal short and irregular stricture at distal common bile duct (red arrows). Final diagnosis: malignant distal common bile duct stricture

9. Endoscopic retrograde cholangiopancreatography (ERCP): Double Duct Sign

10. Introduction Worldwide , ranks 13th in incidence. I t constitutes 2–3% of all cancers 6 th leading cause of cancer Mortality in UK and 4 th in US. Worst prognosis of all malignancies.

11. Anatomy

12. Relations

13. Classification of Tumors: Malignant – Ductal adenocarcinoma (majority) – Mucinous cystadenocarcinoma. – Acinar cell carcinoma. – Small cell carcinoma. Uncertain malignant potential – Mucinous cystadenoma. – Solid and cystic papillary neoplasms.

14. Periampullary Carcinoma

15. Localization of tumors 60 to 70 percent of exocrine pancreatic cancers are localized to the head 20 to 25 percent are in the body/tail and • the remainder involve the whole organ

16. Ductal Adenocarcinoma Ductal adenocarcinomas arise most commonly in the Head of the gland Typically, metastasizes to Regional lymph nodes , then to Liver and less commonly to Lungs Also directly invade surrounding viscera – Duodenum, Stomach and Colon Metastasize to any surface in abdominal cavity via peritoneal spread ( ascites- ominous prognosis) Spread to skin as painful nodules. Metastasis to bone is uncommon. Rare spread to brain but can produce meningeal carcinomatosis .

17. Risk Factors Demographic factors: Age(65-75). Male. Black Ethnicity. Environment/lifestyle Smoking Genetic factors and medical conditions: Two first-degree relatives with pancreas cancer: relative risk increases 18- to 57-fold Hereditary pancreatitis (50- to 70-fold increased risk) Chronic pancreatitis (5- to 15-fold increased risk) Diabetes mellitus Familial breast–ovarian cancer syndrome

18. Clinical Presentation Early clinical diagnosis difficult due to nonspecific symptoms and subtle in onset. Typically presents as gradual onset of nonspecific symptoms such as anorexia, malaise, nausea, fatigue, and mid-epigastric or back pain. Significant Weight loss characteristic feature. Steatorrhea (fatty stools)– 25 percent Thrombophlebitis – 3 percent MIDEPIGASTRIC PAIN C an be in RHC/LHC depending on location of tumor – Most common presenting symptom – Mild-moderate(1/3rd cases) –severe(1/3rd cases) – More at night – Increased by food intake and lying flat – Often but always radiating to mid back or lower-back

19. PAINLESS OBSTRUCTIVE JAUNDICE Most characteristic sign of CA head of pancreas. Get medical attention before tumor size enlarges to cause pain. Short duration, severe, progressive. Intermittent if necrosis of tumor occurs. preceded by pruritis -skin bile salt deposition– Scratch marks. C lay colored stools. Tea colored/Darkening of urine.

20. Examination Epigastric Mass Non mobile, smooth, soft/hard, (non)tender, not moving with respiration Palpable gallbladder(+clinical jaundice) Courvoisier sign: Non-tender , soft globular, smooth, moving with respiration, mobile horizontally, dull on percussion 25-30 % cases of CA head of pancreas 50 % cases of peri-ampullary CA. Ascites Shifting dullness and fluid thrill + ve .

21. Investigations • CBC – Anemia of chronic disease – Thrombocytosis Liver Function Test –  Raised total/conjugated (van den Bergh’s test)bilirubin –   Raised ALP/GGTP –  Low albumin and altered PT/INR Serum amylase/lipase* – Raised in < 50 % cases of resectable tumor v/s – 25 % cases of irresectable tumor Elevated tumor markers (CA 19-9 or CEA)

22. Hepatomegaly Splenomegaly Palpable S upraclavicular nodes and tumor deposits in the pelvis; when present, they indicate a grim prognosis.

23. Investigations Ultrasound – Bile duct distension – Mass CT scan with IV contrast – Triple phase CT (pancreas protocol) 90% accurate at finding lesions – A scanner takes multiple X-ray pictures, and a computer reconstructs them into detailed images of the inside of the abdomen

24. Endoscopic ultrasound – Help find lesions not seen on CT – Help determine resectability – Excellent way to get Trans duodenal or trans gastric FNAC or Trucut biopsy. MR cholangiopancreatography (MRCP), which can be used to look at the pancreatic and bile ducts, is described below in the section on cholangiopancreatography. MR angiography (MRA), which looks at blood vessels, is mentioned below in the section on angiography.

25. Endoscopic retrograde cholangiopancreatography (ERCP): For this test, an endoscope (a thin, flexible tube with a tiny video camera on the end) is passed down the throat, through the esophagus and stomach, and into the first part of the small intestine. This is usually done while you are sedated (given medicine to make you sleepy). A small amount of dye (contrast material) is then injected into the common bile duct, and x-rays are taken. The x-ray images can show narrowing or blockage in these ducts that might be due to pancreatic cancer. ERCP can also be used to place a stent (small tube) into a bile or pancreatic duct to keep it open if a nearby tumor is pressing on it.

26. Staging

27. Surgery Typically, extra-pancreatic disease precludes curative resection and surgical treatment may be palliative at best. Invasion of SMV/portal vein NOT absolute contraindication. – Can be resected partially with as much as 50 % narrowing of lumen. – Complete reconstruction is possible e.g. using native veins as replacement( internal jugular, greater saphenous or splenic) Invasion of SMA/celiac/hepatic arteries still barrier to resection.

28. O perable cases –  Whipple Procedure. – P ylorus preserving pancreaticoduodenectomy (PPPD ) –  Fortner’s regional pancreatectomy (extended whipple’s ) –  Total pancreatectomy . –  Distal pancreatectomy.

29. Whipple Procedure Indicated for peri-ampullary tumors Involves removal of –  Pancreatic head and neck –  40 % distal stomach + C loop of duodenum + 10 cm proximal jejunum –  Lower end of CBD with gall bladder –   Peripancreatic+pericholedochal+paraduodenal+perihepaticnodes Continuity maintained by –   Choledochojejunostomy –   Pancreaticojejunostomy ( or pancreatogastrostomy ) –   Gastrojejunostomy

30. Whipple Procedure

31. Pylorus preserving pancreaticoduodenectomy (PPPD)

32. Survival Incidence Stage23 Incidence Survival/5 years I  8.5% 20% II  23% 10% III  14% 2.5% IV  54% 1.6%

33. Management of Locally Advanced Pancreatic Cancer Conventional external beam radiation therapy. Concomitant Chemo-radiotherapy – 5 -FU – Gemcitabine – Paclitaxel

34. Management of Metastatic Pancreatic Cancer Pain Control – Long-acting narcotics – Neurolytic celiac plexus block (NCPB) • Pancreatic Enzymes Replacement Therapy – PPI – Bacterial overgrowth Endoscopic Stenting of Biliary and Pancreatic Obstruction. Chemotherapy 5-FU & Gemcitabine – Median survival times versus 5-FU – Survival rate at 12-months – Toxicities – Optimizing efficiency Combination Chemotherapy Trials going on.