pancreatic carcinoma

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?