pancreatic carcinoma
TRANSCRIPT
CARCINOMA PANCREAS
PRESENTED by---Dr.JYOTINDRA SINGHMBBS,MS (Gen Surgery) ,M.Ch( Cardiac Surgery)
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
Whipple Procedure - 3D Medical Animation_(360p).avi
INTRODUCTIONCarcinoma 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 colonLeast 5 years survival rate of 3 %.Incidence rate is virtually identical to the mortality rate
INTRODUCTIONPancreatic 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
ANATOMY AND RELATION OF PANCREASPancreas is a long retroperitoneal organ 15 to 20 cm in length.
Weighs about 80 gms ,lies against L1 & L2 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
Cuddles L Kidney
Tickles Spleen
Cradles Aorta
Opposes IVC
Dallies withR RenalPedicle
Hugs the duodenum
Wraps the SMV
Hides behind peritoneum
Durman
BLOOD SUPPLYPANCREATIC BRANCHES OF SPLENIC ARTERY
SUPERIOR PANCREATICODUODENAL ARTERY
INFERIOR PANCREATICODUODENAL ARTERY
VENOUS DRAINAGE IS INTO SPLENIC VEIN ,SUPERIOR MESENTERIC & PORTAL VEIN
Pancreas anatomy 132 tk_(360p).flv
VENOUS DRAINAGE
PANCREATIC DUCTMain 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 PATTERNDIAMETER OF PANCREATIC DUCT TAIL - 1 to 2 mm BODY - 2 to 3 mm
HEAD - 3 to 4 mmUpto 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
Duct of Wirsung
Duct of Wirsung
Duct of Wirsung &Duct of Santorini
Incidence
INCIDENCEAnnual incidence 10 new cases per 100000 populationLowest incidence – India and Middle EastIncidence increases steadily with age – with 80 % over 6th decade of lifeMale: Female ratio – 2:1Pre and post menopausal women ratio is 2: 1
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
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
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
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%
Oncogenes in pancreatic cancer
K ras P 53 P 16 DPC 4
The tumours of the pancreas can be -
A. Non-Endocrine neoplasmsB. Endocrine neoplasms
TUMOURS OF THE PANCREAS
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
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 )
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
Carcinoma - Pancreas
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
HISTOPATH
Case
Case -1
CLINICAL MANIFESTATIONS It is unfortunate that malignant pancreatic cancers are
asymptomatic until local or systemic complication develop.
1. Obstruction to bile duct – Jaundice and pruritus2. Obstruction to duodenum /stomach- Gastric outlet obstruction3. Ulceration- Gastro intestinal haemorrhage4. Infiltration of peripancreatic nerve roots produce pain
The onset of symptoms are insidious and progressiveAbdominal pain is usually post prandial and in epigastriumPain in upper back denotes retroperitoneal extension
Pancreatic Tumors in the HeadTumors in the head may compress biliary ducts or pancreatic ducts
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
PANCREATIC TUMOURS IN TAIL
CARCI NOMA OF BODY AND TAIL
WEIGHT LOSSDEEP SEATED PAINJAUNDICE- < 10 % OF PATIENTSUDDEN ONSET OF DIABETES MELLITUS-25% OF PATIENTMIGRATORY THROMBOPHLEBITIS- OCCURS IN ABOUT 10% PATIENT
SYMPTOMS AND SIGNS
CARCINOMA OF AMPULLA OF VATER
1. Pain occurs less frequently – usually its colicky2. Jaundice is often intermittent3. Chills and fever – due to associated cholangitis
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
Periampullary carcinoma
The individual components of peri ampullary tumors differ in their prognosis
Duodenal carcinoma Ampullary carcinoma CBD growth Pancreatic ca
Site Pancreatic head-2/3rd
Remaining part 1/3rd
Clinical presentation Mid epigastric pain radiating to back Weight loss Fatigue Anorexia Symptoms are vague and hence the delayed
presentation
Clinical presentation Painless progressive jaundice 50-60% Pruritus Staetorrhea Malabsorption New onset of Diabetes in older patients
Clinical presentation Jaundice is a late presentation in uncinate
process growth
Severe back pain indicate irresectablity and an omnious sign
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
Physical findings Palpable GB (Courvoisier’s law) Hepatomegaly Icterus Scratch marks Ascites Mass Virchow’s node Pelvic deposit Trousseau’s sign
Courvoisier Law
Assessment Confirm the diagnosis Stage the disease Assess the operability General assessment for surgery
Have A Great Day…
Investigation CBC LFT RFT Coagulation profile CXR ECG Echo
USG Cheap Level of obstruction Cause of obstruction Liver metastasis Ascites
pancreas tumor( metastatic form carcinoma in stomach )_(360p).avi
USG Operator dependent Miss small metastasis Cannot assess operability
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
CT Focal or diffuse mass lesion which is hypo
dense (low attenuation) and hypo vascular (poor contrast enhancement)
Dilated MPD and CBD
Pancreas
“Operability is assessed in the office of the surgeon and not in the Operating room”
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
MRI Advantages
No radiation Avoids contrast Single investigation that gives all the
information needed
Disadvantages Cost & availability Surgeons are unfamiliar
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
Role of Biopsy
Not mandatory
Role of Biopsy Tissue diagnosis is indicated in cases which
are found inoperable by imaging
Biopsy is indicated when Neoadjuvant chemotherapy is planned
Why not a biopsy May upstage the disease Complications of biopsy Has a very low negative predictive value
What biopsy
Ideally it should be done under EUS guidance Targeted No tumor seeding No complications
like fistula
ERCP
Double duct sign
Not routinely done in pancreaticCancer
Preop biliary drainage
Atypical lower CBD obstruction
PET It is useful in differentiating pancreatic cancer
from chronic Pancreatitis
Extra pancreatic disease
EUS Ideal method to evaluate
lower CBD obstruction
Guided FNAC
Vascular invasion
EUS+FNAC= sensitivity of 90% and specificity of 95%
Angiography
No longer used
Barium studies – only historical
Pad sign – widening of C loop
Reverse 3 sign or Frostberg sign
Tumor markers CA 19-9 CEA CA 125 CA 50 SPAN-1 DUPAN-2
Staging TX primary tumor cannot be assessed
T0 no evidence of primary tumor
T1 confined to pancreasT1a less than 2 cmT1b more than 2 cm
T 2 tumor extend to involve the bile duct, duodenum and peripancreatic tissue
T3 involvement of stomach, spleen, colon, vessels
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
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
Prognosis Tumor size
Node positivity
Type of resection (R0 or R1)
Operability Ca head 20%
Ca body&tail 3%
Ampullary 80%
Preop preparation Vitamin K
Hydration
Correction of electrolytes
Preop nutrition
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
Pancreaticoduodenectomy
Pancreaticoduodenectomy offers the surgeon the only chance to cure a patient with carcinoma of the head of the pancreas and periampullary region
“Pancreaticoduodenecomy is the Cadillac of operations”
but
“It is not a Cadillac that he ( surgeon) is driving but a formula 1 Ferrari”
Attitude of the surgeon towards pancreatic cancer
Nihilistic
Activist
Realist
Sir Allen O Whipple
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
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
Pancreaticoduodenectomy – consecutive series without mortality
J Howard-41 cases1968
J Cameron145 cases1993
Aranha152 cases2003
Michael Trede- 118 cases 1990
OPERATIVE STEPSIncision- transverse subcostal / midlineExploration/mobilization- kocherizationCholecystectomy/dissection of hepatoduodenal ligamentMobilization of pancreatic neckPartial gastrectomyDivision of pancreasDissection of retropancreatic vesselsDivision of jejunumReconstruction
Whipple – 6 well defined operative steps
1. Cattle Brasch maneuver
2. Extended Kocherization
3. Portal Dissection, division of Bile duct4. Division of Stomach
5. Division of Jejunum
6. Pancreatic Neck transection
Radical Distal Pancreatectomy with Resection_(360p).flv
Reconstruction after Classical Whipple’s operation
Hepaticojejunostomy
Gastrojejunostomy
Pancreaticojejunostomy
LAPAROSCOPIC PANCREATICO-DUODENECTOMY DRAGO FEUNRMF, MANILA PART 3 of 3.avi_(360p).avi
PANCREATICODUODENECYTOMY- PYLORUS PRESERVATIION
Incision- transverse subcostal / midlineExploration/mobilization- kocherizationCholecystectomy/division of the bile ductExposure of superior mesenteric veinDivision of duodenumDivision of gastroduodenal arteryDivision of pancreatic neckDissection of uncinate processResected specimen-gallbladder,distal bile duct,2nd 3rd &4th part of duodenum,proximal jejunum and head ,neck & uncinate portion of pancreasReconstruction
Pylorus preserving Pancreaticoduodenectomy
Reconstruction after PPPD
Duodenum- preserving resection of the head of pancreas
Incision- transverse subcostal / midlineExploration/mobilization- kocherizationExposure of the pancreasDissection of the neck of pancreasResection along the CBDPancreatic remnantReconstructionBile duct anastomosisStenosis of the pancreatic duct
TOTAL PANCREATECTOMY
This involves the en bloc resection of
The whole of pancreasThe spleenDistal half of stomachDuodenumProximal 10 cm of jejunumGall bladderCystic and common bile duct
TOTAL PANCREATECTOMY
Incision- Transverse muscle-cuting incisionExploration/mobilization- kocherizationMobilization of duodenum/head of pancreasExposure of body and tail of pancreasDissection of the vessels- hepatic artery is tracedMobilization of spleen and pancreasLimited gastrectomy/pylorus preserving resectionReconstruction – choledochojejunostomy/bowel anastomosis
Pancreas_Totally Laparoscopic Pancreatectomy._(360p).avi
Total Pancreatectomy Reconstruction
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
Radical Pancreatic Surgery with Vascular Resection. Emilio V_(360p).flv
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-IENUCLEATION- CUSADISTAL PANCRETECTOMY
PANCREATIC CANCER- LAPROSCOPIC STAGING
7.5 Mhz linear array transducerPort-infraumbilical and right flankSearch for serosal depositLesions on liver sampled/GB visualisedTransducer placed on porta hepatisLook for dilataion of pancreatic ductPosition of tumour relative to pancreatic duct/portal veinLymphnodes more than 10 mm -significant
PANCREATIC TRANSPLANTATION
Suitable donors between 20 and 50 yrsPancreatic blood flow to be maintained- warm ischemiaGland should be perfused with a cold preservation fluid- hypertonic citrate solutionPancreas 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
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
Controversies Role of octreotide Order of reconstruction Adjuvant therapy Palliative resections Palliative bypass
Preop biliary drainage For
Reduce the mortality and morbidity of surgery Improves the liver function Reduces the bleeding Improves the nutrition Buys time
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
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
Preop biliary drainage - consensus
Routine preop biliary drainage is not recommended and there is no evidence to support it
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
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
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
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
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
Vascular involvement
Resection of SMV is accepted provide it enables to perform R0 resections
Involvement of SMA is a contraindication for resection
Extended lymphadenectomy
Studies have shown that extended lymphadenectomies can be done with acceptable morbidity
Extended lymphadenectomy do not improve the survival
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
Adjuvant therapy Chemotherapy
Radiotherapy
Chemo radiotherapy
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
Palliation Jaundice (pruritus) Duodenal obstruction Pain Bleeding
Palliative resections – Is it acceptable
Palliative resections and palliative bypass has the same survival
Hence palliative resections are not accepted
Palliative resections The series from John Hopkins has shown
survival benefits in R1 and few cases of R2 Whipple
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
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
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
Palliative bypass Options of by-pass
Choledochojejunostomy ( Loop or Roux en Y) Cholecystojejunostomy Hepaticojejunostomy
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
Laparoscopy in palliation Depending on the expertise of the surgeon,
procedures can be done with laparoscopy
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
ROBOTIC SURGERIES
ROBOTIC ASSISTED LAPAROSCOPIC WHIPPLE'S OPERATION FOR_(360p).avi
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 casesPost surgery five year survival rate is least in pancreatic malignancy.tiveNewer approaches are less radical and more effectiveConcept of regional pancreatectomy has increased poet op survival periodSurvival 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.
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
Questions?