Gall bladder cancer

GALL BLADDER CANCER
Dr. Zeeshan
OVERVIEW
 GB cancer is rare – traditionally incurable
 Late presentation
 Disseminated disease
 Dismal prognosis and lack of effective therapy
 Blalock – “ In malignancy of GB, when a diagnosis
can be made without exploration, no operation should
be performed, inasmuch as it only shortens the
patient’s life”
TENDENCY TO SPREAD
 Lymphatics
 Hematogenous
 Peritoneal
 Along biopsy tracts and wounds
 Overall 5 year survival : 5%
 Median survival : < 6 months
 Treatment : Complete surgical resection
EPIDEMIOLOGY
 Highest incidence:
- Females in India : (21.5 per 100,000)
- Females in Pakistan : (13.8 per 100,000)
 In USA : Females ( 2 per 100,000)
 Female : male – 3:1
 Increase in age : increase in incidence
 Obesity : BMI 30 – 34.9 vs 18.5 – 24.9 ---RR of
death from CA GB 2.13
ETIOLOGY
 Most consistent risk factor : Cholelithiasis with
chronic inflammation (75-90%)
 RR of CA GB with stone >3cm – 10.1
 Possibility of stone formation and CA sharing
same risk factors
 Stones may prompt a radiological workup /
cholecystectomy resulting in detection
Gall bladder cancer
CHRONIC INFLAMMATION
 Biliary enteric fistulas
 Typhoid infections
 Pancreaticobiliary malfunctions
 Calcification : PORCELAIN GB
- Type of calcification – degree of risk
Stippled >>>> Diffuse intramural calcification
Gall bladder cancer
CHEMICALS
 OCP
 Methyl Dopa
 INH
 Rubber industry
??ADENOMA- CARCINOMA
SEQUENCE
 Poor association
 No increased risk of malignancy in polyps
ANATOMY OF GALL BLADDER
 GB partially intraperitoneal structure – attached
to liver on segment IV b and V
 Side of GB attached to liver bed – no peritoneal
covering
 “Cystic plate” – fibrous lining
 In simple cholecystectomy – Plane between
muscularis of GB and cystic plate dissected
---INADEQUATE FOR CA GB
Gall bladder cancer
ANATOMY
 Body and fundus : Lies at a distance from major
inflow structures
Limited segmental resection (Segment IV b and
V) adequate
 Infundibulum : Encroaches onto the porta
hepatis
Tumors of this area – involves porta
Prepare to perform bile duct resection/ major
hepatic resection
LYMPHATICS
PATHOLOGY AND STAGING
 Fundus – 60% of tumors
 Body – 30% of tumors
 Neck – 10% of tumors
 Gross findings:
- Typical of chronic cholecystitis
- Tumors in lower end of GB obstructing –
HYDROPS
- Advanced tumors in neck/infundibulum –
jaundice / vascular invasion/ hepatic atrophy
GROSS DESCRIPTIONS
 Infiltrative
 Nodular
 Combined nodular infiltrative
 Papillary - Better prognosis
 Combined papillary infiltrative
PAPILLARY ADENOCARCINOMA
HISTOLOGY
 Adenocarcinoma – 89.4%
 Squamous / Adenosquamous – 4%
 Neuroendocrine – 3%
 Sarcoma/Adenosarcoma – 1.6%
 Melanoma - <1%
CLINICAL PRESENTATION
 SCENARIOS:
1. Final pathology after routine cholecystectomy
identifies CA GB
2. GB cancer discovered intraoperatively
3. GB cancer suspected before surgery
HISTORY
 Constant RUQ pain – rather than episodic
crampy pain of biliary colic
 Elderly patients
 Weight loss
 Anorexia
 Jaundice
COMMON SYMPTOMS AND SIGNS
LAB EXAMINATION (HELPFUL IN
ADVANCED DISEASE)
 Anemia
 Hypoalbuminemia
 Leukocytosis
 Elevated bilirubin
 Elevated Alkaline Phosphatase
 Tumor markers:
- CEA : 90% specific but lacks sensitivity (50%)
- CA19-9 : More consistent marker
Sensitivity : 75%
Specificity : 75%
RADIOLOGY
 USG : Excellent modality for GB
 Findings :
- Discontinuous mucosa
- Echogenic mucosa
- Submucosal echogenicity
 Doppler assessment of blood flow: Differentiates
malignant from benign
 Limitation : Unable to stage (Nodes cannot be
visualised)
CT/MRI
 Can assess extent of disease
 Detects presence of distant metastases
 MC finding : Mass in GB
 Assessment of LN:
- Size > 1cm
- Ring like heterogenous enhancement
Gall bladder cancer
CT/MRI
 CT : 71 – 84 % accurate
• 79% can differentiate between T1 and T2
• 93% between T2 and T3
• 100% between T3 and T4
 MRI:
- 70 – 100% sensitive for hepatic invasion
- 60 – 75% sensitive for LN spread
 FDG PET scan :
- More accurate than CT in diagnosing metastatic
disease
- Poor in differentiating benign inflammatory state
vs malignancy
Gall bladder cancer
PRE-OPERATIVE PATHOLOGICAL
DIAGNOSIS
 If CA-GB suspected on clinical and radiological
grounds – Histological diagnosis NOT necessary
 Biopsy increases risk of seeding
 If concern for GB malignancy significant –
Unwise to perform simple cholecystectomy
 For unresectable disease – Percutaneous needle
biopsy – 90% accurate
BILE CYTOLOGY
 Less risky way of making diagnosis without risk
of peritoneal seeding.
 Justifiable in patients undergoing ERCP/PTC
 If NOT - unwarranted
Gall bladder cancer
STAGING
Gall bladder cancer
SURGICAL MANAGEMENT
 Benign polyp :
- Adenomatous polyp – ONLY polypoidal lesion
with malignant potential
- Cholesterol polyp – MC polyp
 Indicators for cholecystectomy:
- Single polyp
- Size > 1 cm
- Age > 50 years
 Old concept – Offer OPEN cholecystectomy
 Current concept – Offer Laparoscopic
cholecystectomy + Frozen
 Diagnosis – USG required
 If polyp presents with abdominal pain – rule out
other causes
INCIDENTALLY DETECTED GB CA
 Incidence : 0.27 – 2.1%
 If diagnosis made by frozen – Prepare for
curative resection
 IF NOT COMFORTABLE – REFER
NO EFFECT ON OUTCOME
 T1a with margins negative : Standard
cholecystectom cures 85 – 100%
 T1b – controversial
 T2 onwards – plan liver resection
NON CURATIVE
CHOLECYSTECTOMY
 Careful work up required which includes :
- Reviewing pre-cholecystectomy USG to localise
extent
- Discuss case with operating surgeon
- Re-review T stage and margins pathologically
T1B LESIONS
 If cystic duct stump / margins +ve –
Bile duct resection and reconstruction
OR
Re-resection of cystic duct stump and frozen
proceed
EXTENT OF RESECTION BY STAGE
 Rational approach to CA GB depends on :
- Stage of disease
- Location of tumour
- Margins status – if cholecystectomy has already
been performed.
- Whether a prior noncurative cholecystectomy has
been performed
 T1a – Simple cholecystectomy
 T1b – Higher locoregional recurrence rates after
simple cholecystectomy
 T2,T3 – Complete enbloc resection with segment
Ivb and V of liver
 If invasion of hepatic inflow vascular structures
is documented :
- Extended right hepatectomy + LN clearance of
hepatoduodenal ligament + negative cystic
duct/bile duct margins
- Abandon major resection IF:
1. Nodal spread
2. Metastases
LIVER RESECTION
 Goal : To ensure a margin of 1-2 cm
 Anatomic resection – better than wedge resection
 If excision of segment IV b and V inadequate –
DO extended right hepatectomy:
 ESP in cases of large tumors invading portal
pedicle
 Tumors of lower end of GB encroaching onto
porta
 If isolated invasion of organ system present
EG: Stomach , duodenum, colon
In absence of distant metastases – DO local
resection
LYMPH NODAL DISSECTION
 Weigh risks vs benefits
 Range of operations include : Excision of cystic
duct node– Portal clearance–
pancreaticoduodencetomy
 1st
manouvre : Mobilisation of duodenum – To
assess aortocaval and retropancreatic nodes
 Assess celiac node LN – If suspicious DO frozen
and terminate procedure IF MALIGNANT
WHETHER ROUTINE BILE DUCT
RESECTION IS NECESSARY FOR
ADEQUATE LN CLEARANCE??
 Excising extrahepatic bile duct – makes LN
dissection easy
 Increases morbidity of operation
 No difference noted in the number of LN
harvested with OR without bile duct resection
 In general – bile duct resection NOT needed----
Unless suspicion of PORTA infiltration
 Stage of disease and NOT extent of resection
determines survival of patients
Gall bladder cancer
DID YOU KNOW?
 “Honeymoon and alcohol”
 Roots trace back to Babylon
 Tradition for the soon to be father- in-law to
supply his daughter’s fiance with a month of
mead
 Time period referred to as the HONEYMONTH
Gall bladder cancer
DID YOU KNOW?
 Adolf Hitler was one of the world’s best known abstainers from
alcohol.
Gall bladder cancer
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Gall bladder cancer

  • 2. OVERVIEW  GB cancer is rare – traditionally incurable  Late presentation  Disseminated disease  Dismal prognosis and lack of effective therapy  Blalock – “ In malignancy of GB, when a diagnosis can be made without exploration, no operation should be performed, inasmuch as it only shortens the patient’s life”
  • 3. TENDENCY TO SPREAD  Lymphatics  Hematogenous  Peritoneal  Along biopsy tracts and wounds  Overall 5 year survival : 5%  Median survival : < 6 months  Treatment : Complete surgical resection
  • 4. EPIDEMIOLOGY  Highest incidence: - Females in India : (21.5 per 100,000) - Females in Pakistan : (13.8 per 100,000)  In USA : Females ( 2 per 100,000)  Female : male – 3:1  Increase in age : increase in incidence  Obesity : BMI 30 – 34.9 vs 18.5 – 24.9 ---RR of death from CA GB 2.13
  • 5. ETIOLOGY  Most consistent risk factor : Cholelithiasis with chronic inflammation (75-90%)  RR of CA GB with stone >3cm – 10.1  Possibility of stone formation and CA sharing same risk factors  Stones may prompt a radiological workup / cholecystectomy resulting in detection
  • 7. CHRONIC INFLAMMATION  Biliary enteric fistulas  Typhoid infections  Pancreaticobiliary malfunctions  Calcification : PORCELAIN GB - Type of calcification – degree of risk Stippled >>>> Diffuse intramural calcification
  • 9. CHEMICALS  OCP  Methyl Dopa  INH  Rubber industry
  • 10. ??ADENOMA- CARCINOMA SEQUENCE  Poor association  No increased risk of malignancy in polyps
  • 11. ANATOMY OF GALL BLADDER  GB partially intraperitoneal structure – attached to liver on segment IV b and V  Side of GB attached to liver bed – no peritoneal covering  “Cystic plate” – fibrous lining  In simple cholecystectomy – Plane between muscularis of GB and cystic plate dissected ---INADEQUATE FOR CA GB
  • 13. ANATOMY  Body and fundus : Lies at a distance from major inflow structures Limited segmental resection (Segment IV b and V) adequate  Infundibulum : Encroaches onto the porta hepatis Tumors of this area – involves porta Prepare to perform bile duct resection/ major hepatic resection
  • 15. PATHOLOGY AND STAGING  Fundus – 60% of tumors  Body – 30% of tumors  Neck – 10% of tumors  Gross findings: - Typical of chronic cholecystitis - Tumors in lower end of GB obstructing – HYDROPS - Advanced tumors in neck/infundibulum – jaundice / vascular invasion/ hepatic atrophy
  • 16. GROSS DESCRIPTIONS  Infiltrative  Nodular  Combined nodular infiltrative  Papillary - Better prognosis  Combined papillary infiltrative
  • 18. HISTOLOGY  Adenocarcinoma – 89.4%  Squamous / Adenosquamous – 4%  Neuroendocrine – 3%  Sarcoma/Adenosarcoma – 1.6%  Melanoma - <1%
  • 19. CLINICAL PRESENTATION  SCENARIOS: 1. Final pathology after routine cholecystectomy identifies CA GB 2. GB cancer discovered intraoperatively 3. GB cancer suspected before surgery
  • 20. HISTORY  Constant RUQ pain – rather than episodic crampy pain of biliary colic  Elderly patients  Weight loss  Anorexia  Jaundice
  • 22. LAB EXAMINATION (HELPFUL IN ADVANCED DISEASE)  Anemia  Hypoalbuminemia  Leukocytosis  Elevated bilirubin  Elevated Alkaline Phosphatase  Tumor markers: - CEA : 90% specific but lacks sensitivity (50%) - CA19-9 : More consistent marker Sensitivity : 75% Specificity : 75%
  • 23. RADIOLOGY  USG : Excellent modality for GB  Findings : - Discontinuous mucosa - Echogenic mucosa - Submucosal echogenicity  Doppler assessment of blood flow: Differentiates malignant from benign  Limitation : Unable to stage (Nodes cannot be visualised)
  • 24. CT/MRI  Can assess extent of disease  Detects presence of distant metastases  MC finding : Mass in GB  Assessment of LN: - Size > 1cm - Ring like heterogenous enhancement
  • 26. CT/MRI  CT : 71 – 84 % accurate • 79% can differentiate between T1 and T2 • 93% between T2 and T3 • 100% between T3 and T4  MRI: - 70 – 100% sensitive for hepatic invasion - 60 – 75% sensitive for LN spread
  • 27.  FDG PET scan : - More accurate than CT in diagnosing metastatic disease - Poor in differentiating benign inflammatory state vs malignancy
  • 29. PRE-OPERATIVE PATHOLOGICAL DIAGNOSIS  If CA-GB suspected on clinical and radiological grounds – Histological diagnosis NOT necessary  Biopsy increases risk of seeding  If concern for GB malignancy significant – Unwise to perform simple cholecystectomy  For unresectable disease – Percutaneous needle biopsy – 90% accurate
  • 30. BILE CYTOLOGY  Less risky way of making diagnosis without risk of peritoneal seeding.  Justifiable in patients undergoing ERCP/PTC  If NOT - unwarranted
  • 34. SURGICAL MANAGEMENT  Benign polyp : - Adenomatous polyp – ONLY polypoidal lesion with malignant potential - Cholesterol polyp – MC polyp  Indicators for cholecystectomy: - Single polyp - Size > 1 cm - Age > 50 years
  • 35.  Old concept – Offer OPEN cholecystectomy  Current concept – Offer Laparoscopic cholecystectomy + Frozen  Diagnosis – USG required  If polyp presents with abdominal pain – rule out other causes
  • 36. INCIDENTALLY DETECTED GB CA  Incidence : 0.27 – 2.1%  If diagnosis made by frozen – Prepare for curative resection  IF NOT COMFORTABLE – REFER NO EFFECT ON OUTCOME
  • 37.  T1a with margins negative : Standard cholecystectom cures 85 – 100%  T1b – controversial  T2 onwards – plan liver resection
  • 38. NON CURATIVE CHOLECYSTECTOMY  Careful work up required which includes : - Reviewing pre-cholecystectomy USG to localise extent - Discuss case with operating surgeon - Re-review T stage and margins pathologically
  • 39. T1B LESIONS  If cystic duct stump / margins +ve – Bile duct resection and reconstruction OR Re-resection of cystic duct stump and frozen proceed
  • 40. EXTENT OF RESECTION BY STAGE  Rational approach to CA GB depends on : - Stage of disease - Location of tumour - Margins status – if cholecystectomy has already been performed. - Whether a prior noncurative cholecystectomy has been performed
  • 41.  T1a – Simple cholecystectomy  T1b – Higher locoregional recurrence rates after simple cholecystectomy  T2,T3 – Complete enbloc resection with segment Ivb and V of liver
  • 42.  If invasion of hepatic inflow vascular structures is documented : - Extended right hepatectomy + LN clearance of hepatoduodenal ligament + negative cystic duct/bile duct margins - Abandon major resection IF: 1. Nodal spread 2. Metastases
  • 43. LIVER RESECTION  Goal : To ensure a margin of 1-2 cm  Anatomic resection – better than wedge resection  If excision of segment IV b and V inadequate – DO extended right hepatectomy:  ESP in cases of large tumors invading portal pedicle  Tumors of lower end of GB encroaching onto porta
  • 44.  If isolated invasion of organ system present EG: Stomach , duodenum, colon In absence of distant metastases – DO local resection
  • 45. LYMPH NODAL DISSECTION  Weigh risks vs benefits  Range of operations include : Excision of cystic duct node– Portal clearance– pancreaticoduodencetomy  1st manouvre : Mobilisation of duodenum – To assess aortocaval and retropancreatic nodes  Assess celiac node LN – If suspicious DO frozen and terminate procedure IF MALIGNANT
  • 46. WHETHER ROUTINE BILE DUCT RESECTION IS NECESSARY FOR ADEQUATE LN CLEARANCE??  Excising extrahepatic bile duct – makes LN dissection easy  Increases morbidity of operation  No difference noted in the number of LN harvested with OR without bile duct resection  In general – bile duct resection NOT needed---- Unless suspicion of PORTA infiltration
  • 47.  Stage of disease and NOT extent of resection determines survival of patients
  • 49. DID YOU KNOW?  “Honeymoon and alcohol”  Roots trace back to Babylon  Tradition for the soon to be father- in-law to supply his daughter’s fiance with a month of mead  Time period referred to as the HONEYMONTH
  • 51. DID YOU KNOW?  Adolf Hitler was one of the world’s best known abstainers from alcohol.