1. The Curious Case of John Dick Group 3 Clinical Clerk Batch 2012 SY 2011-2012

2. Objectives  To discuss an intriguing case of an elderly woman with abdominal pain  To elaborate on the approach to jaundice  To discuss the diagnostic approaches to jaundice  To present the management of obstructive jaundice and review therapeutic options

3. Identifying Data  L.S.  64-year-old  Widow  Vegetable vendor  Tondo, Manila

4. Chief Complaint Generalized jaundice of 1 month duration

5. 6 mos PTA 4 wks PTA 2 wks PTA 4 days PTA 1 wk PTAAdmission Colicky Abdominal Pain Temporal Profile Weight loss Jaundice Tea-colored urine Loss of appetite

6.  Past Medical History :  Osteoarthritis, right ankle – took unrecalled medication for 1 month  Exposure to Tuberculosis  G 4 P 4 (4004) via NSD without complications  No history of cancer  No history of heart failure or valvular defects  No history of Hepatitis B or C  No hemolytic disorders  No dyslipidemia  No history of blood transfusion  No history of needle prick injury  No history of prolonged or high-dose intake of drugs (e.g. Quinacrine, Rifampicin, etc)  No previous hospitalization, surgery, dental surgery

7.  Family History  Tuberculosis – Mother  No history of Cancer  No history of hemolytic disorders  Social History :  Non-smoker, non-alcoholic beverage drinker  No IV illicit drug use

8. Review of Systems  Weight loss (~50 kg  ~36 kg in 1 month)  No weakness  No persistent cough, night sweats, hemoptysis, fever  No edema, difficulty of breathing, orthopnea  No breast lump, pain or discharge  No abnormal vaginal bleeding  No history of abdominal trauma, changes in bowel movement, nausea and vomiting, fatty food intolerance

9. Physical Examination GeneralAwake, conscious, coherent, not in pain, appears ill-looking Vital Signs BP 90/50 mmHg HR 64 bpm Ht 154 cm RR 18 cpm T 36.4 0 C Wt 36 kg BMI 15.1 kg/m 2 HEENT Icteric sclerae, yellowish palpebral conjunctivae, yellowish oral mucosa, no tonsillopharyngeal congestion, no cervical lymphadenopathies ChestEqual chest expansion, no retractions, clear breath sounds, No spider angioma CVSAdynamic precordium, normal rate, regular rhythm, distinct S1 and S2, no murmurs, concordant apex beat and PMI at 5 th ICS LMCL

10. Physical Examination Abdomen Globular, No caput medusae, No bulging flanks, Abdominal girth = 29 inches Normoactive bowel sounds, Tympanitic, Soft, Positive direct tenderness over epigastric area, No palpable masses, Liver span = 9cm, Spleen not palpable, No fluid wave, No shifting dullness, Negative Murphy’s sign

11. Physical Examination ExtremitiesFull and equal pulses, no edema, no cyanosis, Generalized jaundice Mental Status Exam Oriented to person, place and time. Remote, recent past, immediate memory not impaired. Cranial NervesIntact Motor, Sensory, Cerebellar Intact

12. Pertinent Findings PositiveNegative Weight lossDrug or alcohol use Abdominal enlargementBlood transfusion or donation JaundiceTattoos or IV illicit drugs Tea-colored urineHistory of Hepatitis AnorexiaFamily history of Hemolytic disordes Changes in bowel movement Nausea and vomiting Fever Fatty food intolerance History of abdominal trauma

13. Pertinent Findings PositiveNegative Icteric scleraeFluid wave, shifting dullness, bulging flanks JaundiceSpider angioma, caput medusae Globular abdomen, softHepatomegaly Splenomegaly Murphy’s sign

14. Assessment  Primary Impression  Obstructive Jaundice secondary to Pancreatic Head Mass  Differential Diagnoses:  TB Lymphadenitis  Peribiliary cancer  Choledocholithiasis

15. JAUNDICECAROTENEMIA DRUG INTAKE OF PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA EXCESSIVE PRODUCTION (Hemolytic Anemia) IMPAIRED CLEARANCE UPTAKE/CONJUGATIONEXCRETIONHEPATICPOST-HEPATIC

16. Jaundice Carotenemia DRUG INTAKE PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA Excessive intake of carotene containing food such as carrots, leafy vegetables, squash, peaches, and oranges Yellowish discoloration concentrated on palms, soles, forehead & nasolabial folds

17. Jaundice Carotenemia DRUG INTAKE PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA Excessive intake of carotene containing food such as carrots, leafy vegetables, squash, peaches, and oranges Yellowish discoloration concentrated on palms, soles, forehead & nasolabial folds

18. Jaundice Carotenemia DRUG INTAKE PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA

19. Jaundice Carotenemia DRUG INTAKE PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA

20. Jaundice Carotenemia DRUG INTAKE PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA

21. Jaundice Carotenemia DRUG INTAKE PROBENECID/ RIFAMPICIN HYPERBILIRUBINEMIA (+) Jaundice (+) Tea-colored urine (+) yellow discoloration of the skin (+) Icteric sclerae (-) Murphy’s sign (-) fluid wave, bulging flanks and shifting dullness (-) spider angioma and caput medusae (-) Hepatomegaly (liver span = 9 cm) (-) splenomegaly

22. HYPERBILIRUBINEMIA EXCESSIVE PRODUCTION (Hemolytic Anemia) IMPAIRED CLEARANCE Ssx of anemia (pallor, fatigue, weakness, dizziness, confusion, shortness of breath, and potential for heart failure) Usually normal colored urine and stool If inherited symptoms should have been present at an earlier age jaundice, splenomegaly, hepatomegaly, tachycardia, murmur

23. HYPERBILIRUBINEMIA EXCESSIVE PRODUCTION (Hemolytic Anemia) IMPAIRED CLEARANCE

24. UPTAKE/ CONJUGATION EXCRETIONHEPATICPOST-HEPATIC

25. IMPAIRED CLEARANCE UPTAKE/ CONJUGATION EXCRETIONHEPATICPOST-HEPATIC Crigler-Najjar syndromes – complete/incomplete absence of UDPGT activity Gilbert’s syndrome – reduced bilirubin UDPGT activity Manifestations of disorders in conjugation should appear earlier

26. IMPAIRED CLEARANCE UPTAKE/ CONJUGATION EXCRETIONHEPATICPOST-HEPATIC

27. (-) spider angioma and caput medusae (-) fluid wave, bulging flanks and shifting dullness (-) Hepatomegaly (liver span = 9 cm) (-) splenomegaly

28. IMPAIRED CLEARANCE UPTAKE/ CONJUGATION EXCRETIONHEPATICPOST-HEPATIC

29. GallbladderBiliary TreePancreasIntestine

30. Primary Impression Obstructive jaundice secondary to Pancreatic head mass r/o pancreatic ductal adenocarcinoma

31. Incidence rate 37,700 cases in the US, leading to 34,300 deaths. No predilection between genders Incidence is more common within the elderly population No established early warning symptoms Overall 5-year survival rate, <5% Pancreatic Adenocarcinoma

32. Causes are still unknown although it is considered that environmental causes play a role: Cigarette smoking Obesity Chronic pancreatitis History of diabetes mellitus Diet (increased intake of red meat or dairy products) Pancreatic Adenocarcinoma

33. Said to arise from a series of gene mutations Early on its onset, the mass would originate within the area of the ductal epithelium and would gradually spread to adjacent areas. Pancreatic intraepithelial neoplasia  invasive carcinoma Activation of the KRAS2 oncogene and inactivation of the tumour suppressor genes CDKN2A and TP53 Pancreatic Adenocarcinoma

34. Presentation of the symptoms would greatly depend on the area where the tumour is located. In 80% of cases, the tumour would be located within the area of the pancreatic head and this would have a great likelihood to cause obstructive cholestasis. Abdominal pain or discomfort as well as nausea are common clinical presentations. Diagnosis and staging

35. Systemic signs would include weakness, weight loss as well as anorexia. Physical examination: Signs of jaundice Wasting Hepatomegaly Ascites Routine laboratory tests might reveal anemia, abnormal liver function tests and hyperglycemia. Pancreatic Adenocarcinoma

36. Common complaints would include abdominal pain with the possibility of radiating to the back. Weight loss Splenomegaly, varices in the stomach and esophagus, GI bleeding DM symptoms, glucose intolerance

37. Differential Diagnoses

38. TB Lymphadenitis  Right hypochondriac pain, epigastric pain and tenderness, jaundice, weight loss, icterisia  Philippines is endemic for Tuberculosis  Involvement of abdomen (one of the common sites of extrapulmonary TB)  No associated or antecedent pulmonary TB (Majority of patients do not have associated or antecedent pulmonary TB)  No splenomegaly or ascites Chronic specific granulomatous inflammation of the lymph node with caseation necrosis

39. Peribiliary Cancer  Jaundice - presenting symptom; intermittently wax and wanes because of necrosis and sloughing or pressure opening of minimally obstructed duct  Progressive weight loss, abdominal pain, loss of appetite  Increased SGOT, SGPT, alkaline phosphatase  Anemia  Elevated Ca 19-9 Tumor arising from the distal common bile duct, duodenum and ampulla of Vater

40. Choledocholithiasis  Epigastric pain that come and go, cramping  Jaundice, tea-colored urine and light- colored stools  Increased SGPT, SGOT, alkaline phosphatase  Dilated bile ducts on ultrasound The presence of stones in the common bile duct

41. ConditionRuling Out Parameters Other Tests Tuberculous Lymphadenitis Low incidence 2:1 male predominance HIV infection increases likelihood Palpable liver Bilirubins Ultrasound/CT Scan ERCP CEA, Ca 19-9 Peribiliary Cancer Choledocholithiasis

42. ConditionRuling Out Parameters Other Tests Tuberculous Lymphadenitis Dyspepsia and vomiting Diarrhea Pruritus Gastrointestinal bleeding Acute Pancreatitis Couvosier sign Hepatomegaly Palpable fixed epigastric mass SGPT and SGOT Alkaline phosphatase CBC Prothrombin time Bleeding and clotting times Urinalysis CA 19-9 Peribiliary Cancer Choledocholithiasis

43. ConditionRuling Out Parameters Other Tests Tuberculous Lymphadenitis No signs of cholecystitis Not totally ruled out by history and PE Serum bilirubins Ultrasound CT Scan ERCP Peribiliary Cancer Choledocholithiasis

44. Laboratory Work-Up

45. 8.16.11Reference Direct Bilirubin223.73.4-13.0 Indirect Bilirubin95.70-18 Total Bilirubin319.48.5-23.6 SGPT/ALT201.900-45 SGOT/AST220.200-35 ALP507.4830-120

47. 8.16.11Reference SGPT/ALT201.900-45 SGOT/AST220.200-35 ALP507.4830-120

48. Tumor Markers

49. CA 19-9  Patients with pancreatic carcinoma, 75-85% have elevated CA 19-9 levels. CA 19-9 value of greater than 100 U/mL is highly specific for malignancy, usually pancreatic. CEA  The reference range is less than or equal to 2.5 mg/mL.  Only 40-45% of patients with pancreatic carcinoma have elevated CEA levels.

50. Clinical Correlation

51. 51

52. Sign / SymptomExplanation Epigastric pain - Likely the result of tumor compression or invasion of mesenteric, celiac, or splanchnic plexuses - Due to obstruction of hollow abdominal viscera Jaundice - Tumor compression of the common bile duct results to failure of conjugated bilirubin to be excreted, causing spillage into the systemic circulation Tea-colored Urine - Since conjugated bilirubin is soluble in water, it would be filtered by the glomerulus and would cause darkening of the urine. Light Stools - Absence or lack of bilirubin in the intestine due to impaired drainage to the duodenum Weight loss - Cancer cells compete with normal cells for nutrients. Also, tumors of the pancreas often interfere with digestion which further contributes to weight loss.

53. Laboratory FindingExplanation Elevated Bilirubins - Due to impaired excretion of bilirubins, secondary to obstructed or compressed ducts Elevated SGOT, SGPT - Accumulation of hydrophobic bile acids cause increased production of free radicals leading to oxidative damage Elevated Alkaline Phosphatase - Injury to the bile ducts will cause a marked increase in the serum alkaline phosphatase since this enzyme is concentrated in the ducts Dilated intra and extrahepatic ducts - Blocking tumor at the head of the pancreas will compress on adjacent ducts and cause dilation proximal to the obstruction Dilated pancreatic ducts - As tumor grows in the back of the head of the pancreas, it causes significant obstruction to the adjacent draining ducts Anemia - Anemia of chronic disease (malignancy)

54. Imaging Studies

55. Ultrasound Findings Pancreatic head Intrahepatic duct dilatation Dilated pancreatic duct Extrahepatic duct dilatation

56. Abdominal CT Scan August 20, 2011 BDM Imaging Center Inc.

57. LIVER STOMACH AORTA LEFT KIDNEY SPLEEN INTRAHEPATIC DUCT DILATED INTRAHEPATIC DUCTS

58. EXTRAHEPATIC DUCT CELIAC ARTERY CELIAC ARTERY AND SMA ARE INTACT DILATED EXTRAHEPATIC DUCT WITH NO EVIDENCE OF OBSTRUCTION

59. LEFT KIDNEY RIGHT KIDNEY GALLBLADDER DUODENUM PANCREAS LIVER ATROPHIC PANCREAS & ENLARGED PANCREATIC HEAD HYDROPS OF THE GALLBLADDER

65. Cholangiogram September 13, 2011 UERMMH

66. Cholangiogram Plain Film Percutaneous tube in the right hemiabdomen. Tip at the right paravertebral area at the level of the L3 vertebra.

67. Cholangiogram Intrahepatic ducts Gallbladder Proximal common bile duct Common hepatic duct Upon injection of contrast...

68. With tube manipulation... Distal portion of the percutaneous tube Duodenum

69. Therapeutics

70.  a.k.a. Pancreaticoduodenectomy Whipple’s procedure

71.  In patients with localized disease (stage I or II disease), with distal metastases excluded by prior CT scan of the abdomen and pelvis, and CT of the chest or chest x-ray, is potentially curative  5-year survival = 10%, although modern series have improved on these results.

72. Chemotherapy  Deoxycytidine analogue gemcitabine  1000 mg/m 2 weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks thereafter

73.  Percutaneous transhepatic biliary drainage is used preoperatively to decompress the biliary tree and prevent complications aggravated by bile spillage.  Drainage of the biliary tree by the introduction of a catheter through the liver and into the biliary tree under radiologic guidance. Also called percutaneous transhepatic cholangiodrainage. Percutaneous Biliary Drainage

74. Indication for PTBD  To relieve obstructive jaundice when the endoscopic retrograde approach has failed or is not indicated

75. Indications for PTBD  To manage infectious complications of biliary obstruction, such as cholangitis and sepsis.  To decompress the biliary tree preoperatively and to assist the surgeon during surgical dissection and reconstructions.

76. Indications for PTBD  As initial step of other bile duct interventions, such as a biopsy of the biliary ducts or peribiliary tumors.  As definitive palliation of biliary stenosis by stent placement.  To provide access for transhepatic brachytherapy for cholangiocarcinoma

77. Percutaneous Biliary Drainage September 2, 2011 St. Luke’s Medical Center

80. Needle Dilated common bile duct

81. Guide wire Cut off area

82. Catheter Gallbladder

83. Biopsy site

84. Prognosis

85.  Median survival time for all patients is 4-6 months.  Patients who survive for 5 years after successful surgery may still die of recurrent disease years after the 5-year survival point.  The occasional patient with metastatic disease or locally advanced disease who survives beyond 2-3 years die of complications

86. Thank you for your kind attention!

87. Appendix

88. CBC8/23 HGB94 HCT26 RBC WBC4.0 Neutrophils61.5 Lymphocytes34.9 Eosinophils3.5 Basophils0 Platelets249 8/23Ref. A/G1.81.1-2.2 Dir. Bilirubin 223.73.4-13.0 Globulin19.715-34 Indir. Bilirubin 95.70-18 Tot. bilirubin 319.48.5-23.6 Tot. protein 55.8560-83 Albumin36.1635-53 Urinalysis ColorDark Yellow TurbidityClear Reaction7.0 Sp. Gr.1.020 ProteinNegative SugarNegative RBC0-1/hpf WBC0-2/hpf Casts Bacteria Epithelial cellsfew 8/8Ref. Na131.80135-145 K4.713.6-5.5 Crea68.7745-104 8/16Reference SGPT201.900-45 SGOT220.200-35 ALP507.4830-120

89.  Gallbladder Pathology  No radiation to right shoulder, no fatty food intolerance, no vomiting, no post-prandial pain, (-) Murphy’s sign  Biliary Tree Pathology  No fatty food intolerance; Not entirely ruled out  Pancreatic Pathology  Non-alcoholic Jaundice