GALL BLADDER CANCERDr. 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

CHRONIC INFLAMMATION

Biliary enteric fistulas Typhoid infections Pancreaticobiliary malfunctions

Calcification : PORCELAIN GB- Type of calcification – degree of risk Stippled >>>> Diffuse intramural calcification

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

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

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

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

STAGING

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 spread2. 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

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

DID YOU KNOW?

Adolf Hitler was one of the world’s best known abstainers from alcohol.