Cancer of Pancreas 1st written by Morgani 1761. USA every year registered 27,000 new cases Frequency 2,2/100,000 in India, Singapore, Kuwait 12,5/100,000 in Sweden Bulgaria 1996 714 cases ( 428 males / 286 females) 8,6/100,000 Men:Women = 1,5 : 1 M/c age group 65 -74 yrs with peak from 65-79 yrs. 63 % patients from Bulgaria unfortunately are diagnosed in III or IV stage. Disease has become more frequent by 200 % over 3-4 decades with peak in the 70s. High risk encountered in males, negros and poor section of the society. In Bulgaria Ca Pancreas 2,76 % of all tumors and 11,4% of all GIT cancer. It takes 7th place as the reason for death with 4,6 %.

Etiology following factors can be considered as initiating or provoking cancer formationi. Tobacco In this the amount of cigarettes is important.

ii. Gammaradiationiii. Post operative after ulcer disease.iv. High level of estrogen and progesterone v. Diet rich in fat and protiens

vi. Diabetesvii. Coffee and Alcohol ingestion more than 10 drinks /day with smoking has importance

viii. Professional risk Workers in metallurgy, chemical ( B-napthylamine, Benzidine) , petrol products.

GENETIC CHANGES : In 1/3rd patients in cells are present diploid DNA ( which has 2 times life expectancy) than 2/3rd with anuploid DNA. This is a important

prognostic factor. Mutation of K-ras gene ( in codon 12) in 80% patients Molecules events on p53.

PATHOANATOMY 75 % in head and neck . 10 % in the tail. ( 90-93 % carcinoma of exocrine portion of gland)

Adenocarcinoma most common. Either mucin or non mucin secreting tu. 4 different forms 1. Ductal cellular “ дуктално-клетъчен” m/c in head of pancreas ; multicentral growth.2. Acinar cellular “ ацинарно- клетъчен” rare form; m/c in young patients3. Cystadenocarcinoma rare4. Papillary rare; m/c females ; low risk of malignancy

Adenocarcinoma lookds greyish white scirrhous or homogenous tumor and replaces the normal yellow lobular structure of the pancreas.

1. Carcinoma of head Adenocarcimoas are most common. These tumors compress the pancreatic and CBD and at times extend directly through the wall of the duodenum to produce small fungating lesion within the duodenum lining. As a result of CBD obstruction ,CBD proxmially becomes distended along with the gallbladder and this gallbladder is distended and palpable “Law of Courvoisiers.” Regional Lymph node metastasis present in 90%

2. Cancer of Body and tail Large, hard and irregular masses that sometimes wipe out the entire tail and body. There tumors frequently extend more widerly than those of the head. They infiltrate into adjacent verterbral column and extend into the retroperitoneal space upwards and downwards and involve spleen or adrenal glands, stomach or transverse colon. Liver invovled in 80% hepatomegaly due to liver metastasis. Such massive metastasis are characteristic for cancer of body and tail and maybe due to the involvment of splenic vein. Regional Lymph node 90% cases.

3. Carcinoma of Ampulla of vater are columnar cell adenocarcinomas. This arises in the duodenal papilla, in ampulla of vater or in the duodenal mucosa adjacent to the papilla. In this carcinoma progessive jaundice may not be seen and intermittent jaundice can present as a feature due to the sloughing of the central portion of tumor at intervals which will relieve obstruction.

CLINICAL1. Painless progressive obstructive jaundice mc in cancer of head. Cancer of body and tail may also present with this only when there is

lymph node enlargement at porta hepatis. The jaundice is slowly progressive and as late symptom .the patient may turn yellow-green in colour.

2. Pruritits Increased bilirubin for 2-3 days before itching starts and this comes as surprise to patient since its nt associated with any pain etc.

3. Intractable pain without jaundice such pain is noticed in cancer of body and tail of pancreas. It is referred to epigastric region with radtion to the back. Pain is often relieved by sitting in hunched position and increased by supine. This is due to the infiltrating tumors towards vertebral column and engaged root nerves of spinal cord. Pain is usually untolerable and controlled with strong analgesics.

4. Loss of weight with anorexia present in all forms. 90% patients.5. Diarrhea with pale and foul smelling stools steatorrhea due enzyme deficiency.6. Urine Dark in colour.7. Syndrome of Trousseau Migrant thrombophlebitis ( in 15% patients months before clinical picture of cancer)8. Diabetes mellitus any patient over age 40 yrs with diabetes and complains sudden weight loss should rise suspection.

Physical examination Jaundice is main sign. Courvoisiers law palpable distended gallbladder . Hepatomegaly.

Clinical symptoms are divided ( разделен) into 2 syndromes :1. Syndrome due to the neoplasm is characterized for all oncological patients and features decreased working capacity, disturbed general status, sleepiness, loss of apetite, loss of weight etc.2. Syndrome due to localization of tumor

Head Choledochocus ( Jaundice) and Wall of duodenum ( Stenosis) vomiting, loss of weight, cant eat. Body & tail Symptoms remain hidden for long time till the time the infiltration process begins towars spinal cord root nerves or

stomach, colon transversum, renal, adrenal, spleen with specific symptoms.

Spread of Cancer 1. Local spread – as described above.2. Lymphatic spread. Head pancreaticoduodenal LN PyloricPorta hepatis LN Hepatic artery LN. Body & tail Inf pancreatic superior pancreatic mesenteric para-aortic LN. coelic gastroc Virchows LN ( left supraclavicular) less commonly affected.

Nomenclature of (A) perigastric lymph nodes in patients with carcinoma of the head of the pancreas and (B) lymph nodes in carcinoma of the head of the pancreas region. 1, right cardiac lymph nodes; 2, left cardiac lymph nodes; 3, lesser curvature lymph nodes; 4, greater curvature lymph nodes; 5, suprapyloric lymph nodes; 6, infrapyloric lymph nodes; 7, lymph nodes around the left gastric artery; 8, lymph nodes around the common hepatic artery; 9, lymph nodes around the celiac trunk; 10, lymph nodes at the hilum of the spleen; 11, lymph nodes along the splenic artery; 12, lymph nodes of the hepatoduodenal ligament; 13, posterior pancreaticoduodenal lymph nodes; 14, lymph nodes around the superior mesenteric artery; 15, lymph nodes along the middle colic artery; 16, para-aortic lymph nodes; 17, anterior pancreticoduodenal lymph nodes; 18, inferior pancreatic body lymph nodes

3. Vascular spread Head very uncommon Body& tail spread towards liver, lungs, brain, bones.

4. Peritoneal implantation resulting in ascites is rare

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Instrumental Diagnosis

Diagnosis. Biochemical tests.1. Bilirubin never rises above

30-35mg/100 ml. ( Higher levels seen in hepatitis)

2. Alkaline phosphatase Increased.3. Serum tranaminsases slightly increased.4. Glucose tolerance test important to

undertake this for diabetes developlment.5. Feature is diversion (отклонение) in ALP

( isoenzyme of Nagao and Regan) , LDH ( isoenzyme LD-4 LD-5),GGT

Marker tests these are important not so much for diagnosis but for determining volume of

operative intervention and followup with it in post operative period to see any recurrences.1. CEA , CA 19-9, CA-195 CEA = carcinoembryonic antigen CA = carbohydrate

antigen

2. POA ( Pancreatic oncofetal antigen)

3. AFP 4. DU-PAN-2 -- sensitivity 93 %

5. GICA ( Gastrointestinal cancer associated antigen) -- (sensitivity 95 %) (specificity 85%)

CEA and CA 19-9 are m/c used but are with low sensitivity and not specific for cancer of pancreas and

not suitable for diagnosis in early stage. CA 19-9 is the most suitable as marker for cancer pancreas

1. Ultrasound : 1st line with screening purpose.Shows change in form, size of gland and its structure and panrenchyma. Shows status of biliary system, gallbladder, Liver, spleen, kidneys.Shows primary tumor, its spread into extrapancreatic space and liver metastasis ( usually missed due to small size)

2. CT SCAN with contrast : shows the small sized metastasis in liver and status of the surrounding organs ( much better than the USG)3. MRI : shows same as CT4. ERCP and PTC : role in mechanical jaundice as used for differential diagnosis of cancer of head of pancreas and cancer of the bile ducts.Shows pancreatic flow obstruction, stenosis with irregular “ nepravni” edges , formation of retention cyst before the stenosis. Shows diagnosis and resectablity of ampullary cancer where even biopsy can be taken either through щипка,четков материал,аспирация и цитология на панкреатичен сок.

5. EUS Endoscopic ultrasound : which defines the intraluminal space.

6. целенасочена тънко иглена биопсия FNB– preoperatively gives oppurtunity for cytological material test and define the oncological process. But also should remember that negative result doesnt rule it out. For cytological test pancreatic juice can be extracted after centrifugation.

7.Laparoscopy : same as endoscopy and helpful in showing small metastasis in liver, carcinoma in peritoneum and omentum.

8. Intraoperative : Diagnosis is confirmed again intraoperative. The formation is palpated and the constistency of the tumor, its boundary, status of biliary system, feature of palpating infiltrate. Intraoperative USG, Cholangiography, Fine needle biopsy ( FNB), Choledochoscopy gives chance to define volume of resectablity. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------TNM Staging System American joint committe for Cancer AJCCThe TNM system uses three criteria to judge the stage of the cancer: the tumor itself, the lymph nodes around the tumor, and if the tumor has spread to the rest of the body. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments

Stage 0 Tis, N0, M0

Stage I T1, N0, M0 T2, N0, M0

Stage II T3, N0, M0 ---------------------------------------------------------------------------------

Stage III T1, N1, M0 T2, N1, M0 T3, N1, M0

Stage IVA T4, Any N, M0

Stage IVB Any T, Any N, M1

Histological Classification Cancer of pancreas has following histological types:Malignant : Ductal Cell “ дуктално-клетечен” Acniar Cell ацинарно- клетъчен Papillary mucinous carcinoma Ring type with stone Adenosquamous

Un diffrentiated Muciod

Giant cell Mixed type

Cystadenocarcinoma

Non classified Pancreatico-blastoma Papillary –cystic neoplasm – Tumor

of Frantz

Tumors with Boundary stage of malignancy Mucinous cystic tumor with dysplasia Intraductal papillary mucin tumor with dysplasia Psuedo-papillary solid tumor

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TREATMENT : Surgical treatment has adequate potential for treatment. Resectability of tumor is determined intraoperatively. For full exploration it is neccessary opening the bursa omentalis, of small

omentum and mobilizing for duodenum a.m Kocher. Also should see that following are not engaged : Free V.Mesenterica Sup, Free V. Porta, Free Porta hepatis, Free from invasion

invasion in the retroperitoneal lymph vessel.

Surgical Treatment is divided into 1) RADICAL Only 5% patients unfortunately fall within this since by the time its diagnosed its spread beyond boundaries of surgical resection 2) PALLIATIVE 95 % of patients are treated in this category.

Palliative procedures Indications are :1. Jaundice2. Stenosis of duodenum3. Pain

Contraindications are Ascites Liver metastasis Peritoneal carcinoma

1 ) Mechanical jaundice aim is to decompression of biliary tree which can be achieved in the following way: Cholecysto- Jejunostomy Cholecysto-dudenostomy Cholecysto-Gastrostomy

Choledocho-Duodenostomy Choledocho- Jejunostomy

For choosing from the above, the following things have to be seen age, stage of disease, risk factors.

i) In advanced stage with SHORT life expectancy Cysto-gastrostomy anastomosis is indicated, no matter how much bile will flow into it and that patient will suffer from post operative biliary gastritis.ii) In stage with LONGER life expectancy Bilio-digestive anastomosis is made b/w the biliary system and part of GIT which is further away from the place of primary tumor Hepatico-Jejuno anastomosis , Cholecysto –Jejuno anastomsis ( intreoperative cholangiography done through the cystic duct to show the patency of ducts) Choledocho-Jejuno anastomosis.

Biliodigestive anastomosis have notable operative risk and possible for post operative risk, with lethality due to hepatic insufficiency in the advanced stage and poor general status.iii) In patients with great risk – there are other palliative procedures : 1. Percutaneous Transhepatic Drainage – placed after cholangiography and gives possibility after decreasing of jaundice, for radical resection of tumor in 15-20%. Techincally more suitable is by placement of endoscopic stent and mortality here is 1-2%. Complications include Hemorrahge, Biliary fistula, Cholangitis, Obstruction of endo-prosthesis.

2) Stenosis of duodenum Gastro-entero anastomosis. Its rare condition and occurs in 13-21% cases.This can be done either alone ( самостоятелно) or along with bilio-digestive anastomosis. But here often its observed disturbed post operative motility and increased risk with low life expectancy.

Gastroenteroanastomosis with bilio-digestive anastomosis in 2 staged is associated with much higher risk and mortality of 20%.Prognosis after palliative procedure till 1 year.3) Pain syndrome 3.1) Virsung-Jejuno anastomosis ( Latero- lateral anastomosis a.m Rochelle-Partington )This operation can be combined either with bilio-digestive anastomosis and gastroentero anastomosis. 3.2) Sphlanicectomy and Gangiolotomy In patients who have persistent and disabling pain, but who are poor candidates for resection. This is done by resection of ganglion in the left or right or bi lateral. But in these operation after removing it, the patient stops to feel other pain syndromes in the abdomen related to other emergency situations.This procedure can also be done percutaneously with injection of Cystostatin and Chemical agents ( Spirits) Chemoabalastion of plexsus coeliacus--: is with low operative mortality rate and morbitiy.

Differential Diagnosis Heavy chronic pancreatitis- difficult to DD, since symptoms are same Cysts and pseudocysts Duodenal ulcer , cholecholithiasis, stenosis of papilla, Nephrolithiasis Neoplasm of stomach, colon transeversum, biliary system, left kidney.

RADICAL OPERATIONS. Indications are :-→ When the distal lymph nodes are not involved→ When tumor is not fixed→ When the liver is free from metastasis.

Resectable tumors < 3 cm Ca located at ampulla , head , neck are resectableUnresectable tumors > 5cm Ca located in body are unresectable.

Only 5% of patients unfortunately fall in this category since by the time its diagnosed its spread beyond boundaries of surgical resection!!!!.1st resection of pancreas was done by Allesandro Codi villa Professor in Surgery in Bolonia -1898.

1. Ca head of pancreas 1st dudeno-pancreatic resection W. Kausch 1909,

who resected head of pancreas with part of duodenum, sutured pylorus as stump, made posterior gastroenteroanastomosis and anastomosis of gallbladder with stomach.

1.1 Whipple 1935 made same operation but sutured ductus pancreaticus blindly and placed a drain . In 1935 he published indications and contraindications for this operation and it was published as the operation in his name.

In this operation in dissection stage is resected head of pancreas and part of body + duodenum +Distal ½ of stomach + extrahepatic biliary cannals together with gallbladder.

Restoration stage 10 variants have been published. Standard procedures is with restoration of biliary flow through hepatico-jejunostomy and anastomosis b/w the remanant part of pancreas and jejunum or posterior wall of stomach.

1.2 Pylorous saving operation ( Transverso-Longmire ) in dudeno-pancreactic resection was first time done in 1978.These are only done in cancer of ampulla and patients in stage I. Dudeno-pancreatic resection has significant low lethality and morbidity.

Difficulty in access : main factor hindering resectability is for Ca head of pancreas is the local invasion into adjoining vessels. In such situations Y.G. Fronter made 2 types of wide duodenopancreatic resection or pancreatectomy. In Type I approach towards pancreas is done by resection of segment of Portal Vein.In type II Resection of segment of portal vein + reconstruction of Hepatic artery or Mesenteric superior artery.

Complication Insufficiency of pancreatic anastomosis and development of acute pancreatits most common in 15% patients.Lethality 5-10%In early stage operative intervention prognosis is good. Indication for this operation are patients in Stage I and Stage II.5 years life expectancy after this operation is b/w 14-33%.For Ca head of pancreas 17-21 For Ca ampulla of vater 42 -75 %2. Ca Body and tail 2.1 Distal pancreatectomy or Left sided Hemi-pancreatectomy. Mobilization of tail and body done by dissecting the overlying peritoneum and lifting them from the retroperitoneal bed. Intimate engagment of splenic vessels splenectomy. Resectability is low only 7-8%. Post operative life expectancy 2 years 15%. 5 years ==8%

2.2 Total pancreatecomy Removal of pancreas+ Duodenum + Spleen.This operation is based on the theory which states that recurrence of carcinoma and implantation of cancer cells can occur in the pancreatic duct system. Statistics show that total pancreatectomy doesnot increase the life expectancy significantly and reccurence of metastasis and cancer occurs.Also along with this comes Diabetes , which is hard to control and treated.

Radiotherapy 40 grays External Beam radiation therapy ( EBRT ) is not enough if used alone but its used for palliative to reduce the pain in two forms as Adjuvant thepary after the resection or locally in advanced non resectable tumor.Radiotherapy along 5 Fluorouracil weekly injection possibly increases the effect with local treatment on the tumor and life expectancy with 20 months in comparison to groups without adjuvant thepary.Intra-operative radiation therapy ( IORT ) along with implantation of radioactive material Iodine 125 seeds ( Radioimmunotherapy) also is with increased operative mortality and morbitiy and average life expectancy of 13 months.Chemotherapy : Monotherapy 5-FU / Mitomicin C / Doxirubicin / Streptozotocin/ Phosphamid.Combined Gamcytabin

Combined therapy including agressive resection , intraopertive radiotherapy and intraoperative infusion with Mitomicin C through hepatic artery or portal vein shows good early effect with life expectancy of 1 year ( 86%)

5 year life expectancy in radical operations on pancrease are low - 15-30%

Findings intraoperatively

Findings contraindicating resection 

Liver metastases (any size)

Celiac lymph node involvement

Peritoneal implants

Invasion of transverse mesocolon

Hepatic hilar lymph node involvement

Findings not contraindicating resection 

Invasion at duodenum or distal stomach

Involved peripancreatic lymph nodes

Involved lymph nodes along the porta hepatis that can

   be swept down with the specimen

1: Head of pancreas2: Uncinate process of pancreas3: Pancreatic notch4: Body of pancreas5: Anterior surface of pancreas6: Inferior surface of pancreas

7: Superior margin of pancreas8: Anterior margin of pancreas9: Inferior margin of pancreas10: Omental tuber11: Tail of pancreas12: Duodenum

STAGE I -- PANCREATIC CANCER T1, N0, M0 / T2, N0, M0Only 20% of the patients receiving surgery will be eligible for total resection. The operative mortality rate for a radical pancreatic resection is less than 10%. For suitable patients post-pancreatectomy, fluorouracil plus regional radiation appears to offer a survival advantage. Approximately 40% of such patients whose tumors are confined to the head of the pancreas may be alive at two years, particularly those with T1, N0 tumors.

Standard: Radical pancreatic resection: Whipple procedure (pancreaticoduodenal resection) with or without resection of the superior mesenteric vein Total pancreatectomy when necessary for adequate margins Distal pancreatectomy for tumors of the body and tail of the pancreas Radical pancreatic resection plus postoperative chemotherapy and irradiation

STAGE II + III + IV a PANCREATIC CANCER Stage II pancreatic cancer includes virtually all tumors of the uncinate process. A few patients with stage II pancreatic cancer are technically resectable, but cures have only rarely been reported.More frequently, palliative bypass of biliary obstruction by surgical, endoscopic, or radiologic means should be performed. Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy, or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration. Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.

Standard: 1. Pancreatectomy when feasible, with or without adjuvant chemotherapy and radiation therapy.2. Radiation therapy with or without chemotherapy.3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[6]

STAGE IVB PANCREATIC CANCER The low objective response rate and lack of survival benefit with current chemotherapy indicates clinical trials as appropriate treatment of all newly diagnosed patients. Occasional patients have palliation of symptoms when treated by chemotherapy with well-tested older drugs. A randomized, placebo- controlled trial demonstrated that chemical splanchnicectomy with 50% alcohol at the time of surgical exploration significantly reduces pain, particularly in those patients with preoperative pain.Gemcitabine has demonstrated activity in pancreatic cancer and is a useful palliative agent.Standard:

1. Chemotherapy with gemcitabine or fluorouracil.2. Pain relieving procedures (e.g., celiac or intrapleural block) and supportive care3. Palliative surgical biliary bypass, percutaneous radiologic biliary stent placement, or endoscopically placed biliary stents.

RECURRENT PANCREATIC CANCER Chemotherapy occasionally produces objective antitumor response, but the low percentage of significant responses and lack of survival advantage warrant use of therapies under evaluation.

Standard:1. Chemotherapy: fluorouracil or gemcitabine.2. Palliative surgical bypass procedures, endoscopic or radiologically placed stents. 3. Palliative radiation procedures. 4. Pain relief by celiac axis nerve or intrapleural block (percutaneous).5. Other palliative medical care alone.

The TNM staging system for Pancreatic CancerStage TNM Classification Clinical Classification distribution at diagnosis (%) Median Survival (months) Five-year survival rate(%)0 TIS, N0, M0 Resectable 15 - 20 13 - 18 15.2IA T1, N0, M0        IB T2, N0, M0        IIA T3, N0, M0        

IIB T1- 3, N1*, M0 Locally advanced 40 8 - 9 6.3

III

T4, any N, M0

Any T, any N

       

IV M1 Metastatic 45 4 - 6 1.6

Endocrine Neoplasms

1. Insuliomas Insulin producing adenoma of the Beta Cell is most common. Written by A. Nicholos 1902 and Wilder 1907. Represents about 70-75 % of all endocrine tumors. Due to excessive secretion of insulin from the B-cell there will be CLASSIC TRIAD OF WHIPPLE :-

Attacks of hypoglycemia with blood sugar less than 2,2mmol Attacks with confusion, stupor and loss of coinsciousness and related to fasting or exercise Attacks are promptly relieved by administration of glucose or by feeding.

Pathology 70% are solitary adenomas , 20 % are multiple adenomas and 10% are metastasising tumors. Vary from small size to large size. Encapsulated, firm, yellow-brown nodules that by expansile growth compress the surrounding tissues. 36% present in head 30% in body 33 % in tail. 1% ectopic localization.

Microscopically composed of cords and nests or well differentiated Beta cells. Rupture of the capsule and extension into the surrounding pancreatic tissue is not reliable criteria for malignancy and diagnosis of cancer shouldnot be made in absence of local invasion beyond the pancreas.

Clinical Patient between the 30-60 year age group. If Blood sugar falls rapidly release of epinephrine due to hypoglycemia Sweating, tachycardia, weakness, hunger, trembling. If blood sugar falls slowly produces cerebral symptoms headache, mental confusion, visual disturbance, convulsion, coma. Symptom may last from weeks few years.

Diagnosis 1. Constant hypoglycemia in early morning on empty stomach This is accomplished by testing at 24 hrs or 72 hrs or by stimulating the secretion of insulin , during which blood sugar insulin ( over 50pmol/l) C-peptide ( over 300 pmol/l)2. Immun-histological test of insulin or C-peptide.l3. Ultrasound Transendoscopy and Translaparoscopy.4. CT scan and MRI 5. Selective angiography specific with 90% diagnostic. As the tumors are rich in blood supply and seen in diameter till 1cm.DD Alcohol abuse, Liver insufficiency, Hypophysial and adrenak insufficiency , Fibrosarcoma.TREATMENT Only permanent cure is excision of the tumor. Preoperative

Adequate glucose sol. Given preoperatively in 10% dextrose. ACTH + Cortisone given to prevent hyperthermia during or immediately after the operation ( choice ) Diazoxide 0,200- 0,600 daily inhibits insulin release directly, increases release of glucose from liver and interferes with

peripheral use of sugar. Somatostatins 0,150 -0,300 Daily. Streptozotocin broad spectrum antibiotic to control symptoms of insulioma.

Operation Every portion of the pancreas is carefully examined. Head of the pancreas is mobilized by Kochers manouver. Sometimes ectopic sites can also be present as in stomach, duodenum,jejunum,ilieum,mesentery and omentum.

Simple excision or enucleation is sufficient as most of these are benign. If the tumor is not visualized and detected 2 operations can be done

→ Distal subtotal pancreatectomy:- resection of pancreas to the left of mesenteric vessels. More popular operation.→ Pancreatico-duodenal resection :- Another group of surgeon prefer this method since they believe the small tumors are

much more easily overlooked in the head and neck rather than the tail and body. But this operation carries with it high risk for mortality and morbidity-------------------------------------------------------------------------------------------------------------------------------------------------------------------

2. Zollinger –Ellison Syndrome ( Gastrinoma )

In 1955 Dr. Zollinger described case of patient with bleeding peptic ulcer and non-beta cell ( D-cell) tumor in pancreas. Delta cells secrete somatostatins and gastrin. The gastrin hormone is also secreted from the G cell of the gastric mucosa. Due to tumor in D-cells, gastrinomas excess acid is produced in the stomach.

Pathology 60% of these tumors are malignant and 2/3rd of them have already metastasied when detected. 40% are benign with majority of them adenomas.

MEA –I ( Multiple endocrine adenomatosis) is a condition presenting with adenomas of various endocrine glands. Parathyroid 90% of patients have hyperparathyroidism due to hyperplasia of parathyroid.Pancreatic Islets 70% have gastrinomasAdrenal gland 40% have adrenocortical hyperplasia.Pituatry 30% have pituatry adenoma.Menetrier’s disease - Polyendocrine adenomas and peptic ulceration with giant gastric rugae.Clinical

Majority of patients in 3rd or 4th decade. 75% ulcers occur in usual site within stomach and 1st and 2nd part of duodenum. 25 % ulcers in distal portion of duodenum and jejunum. Most patient present with peptic ulcer disease with diarrhea due to high volume of acid along with neutralization of pancreatic juice. About 2-3 litres of fluid is found in 12 hour nocturnal secretion Overnight resting secretion contains 200 – 300 meq of free HCL acid. Gastric hypersecretion is associated with distressing watery diarrhoea of 2-8 litres of liquid stool daily.

Diagnosis Meausrement of serum gastrin. When serum gastrin is not elevated to great extent , the case maybe diagnosed by gastric pH analysis followed by secretin test. Secretin test This test is done by measuring basal serum gastrin level and then injecting 2 units of secretin/kg of b.w followed by measurement of serum gastrin levels at various periods upto 1 hour. Patient with this disease will show an abnormal elevation of serum gastrin level whereas normal patient should have no change or reduction in serum gastrin level following iv injection of secretin.CT scan or MRI Localization of the tumor.Treatment Medical Rx indicated in patient with gastrinoma associated with MEA and others having metastatic gastrinomas.Medical Rx H2 Blockers , Somatostatins.Surgical Rx --> Indications are :

Metastatic disease should be ruled out CT Patient withou MEA or MEN syndrome.

70% tumors are found in the triangle formed with the apex at cystic duct –CBD junction and the base is formed by the 3rd part of duodenum. Intraoperative USG used to localize the lesion + if any lymph node present it should be biopsed. If USG fails to localize lesion pyloroplasty made and duodenal wall palpated through the lumen to localize isolated duodenal

gastrinomas. Gastrinoma of duodenal wall or in pancreas are enucleation Gastrinoma in tail distal pancreatectomy Multiple lesion Whipple resection. Palliative operation or in whom no lesion is detected Truncal vagotomy + Pyloroplasty.

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------3. Glucagonoma adenoma of the alpha -2 cells Written by Millinson 1974. Rare tumor with high tendency to turn malignant. 50-60%Clinical in 1942 was published about Erythema necroloticans migrans. It is characteristic for Glucagonoma. Its combined with stomatits, loss of weight, diabetes mellitus and IGT. The skin changes dissappear after the operation.Diagnosis test for Serum glucagon level ( over 1000 umol/l without stress) .Treatment Operative.

4.Vipoma Syndrome of Verner-Morrison or Watery-diarrhoea – hypocalcaemia – Achlorhydria ( WDHA syndrome ) It is known as pancreatic cholera. Occurs due to the secretion Vasoactive intestinal polypeptide ( VIP ), pancreatic polypeptide, GI inhibitor peptide and secretin. 1st three cells are secreted by the PP cells of the islets and neoplasm affecting these cells will cause this syndrome 50 % are malignant and 40% are benign cases. 80% localized in the panceas and 20% in the GIT tract. Middle aged females m/c affected Symptoms Profuse diarrhoea with 4-5 litres/day loss and containing 200-400 mEq K+ daily. Treatment resection of tumors.

5.Somatostatinomas rare tumor with typical pancreatic localization or ectopic presence in duodenum.Malignant form common and occurs due tumor in D cells in Islets leads to lowering in secretion of insulin, PP,Glucagon, secretin, CCK,GIP ( as Somatostatin acts as antagonist for all of them) leads to decrease in pepsin and Nacl in stomach , enzymens and HCO3 from pancreas leads to decrease in absorption of fats and water in duodenum.Clinical Symptom from chronic pancreatitis steatorrhea, diarrhoea, cholelithiasis. Patient complains from pain in upper part with balooning, vomiting and loss of wt.Diagnosis Serum somatostatin levels . Treatment Tumor is located with difficulty due to its small size. Taking in mind the malignancy risk resection of pancreas is done.

Cystic Neoplasms of the Pancreas

Passaro's triangle. Typical location of a gastrinoma the head of the pancreas, duodenum, and the lymphatic bed posterior and superior to the duodenum

World Health Organization Classification of Primary Tumors of the Exocrine Pancreas

  A.   Benign  1.   Serous cystadenoma (16%)  2.   Mucinous cystadenoma (45%)  3.   Intraductal papillary-mucinous adenoma

(32%)  4.   Mature cystic

teratoma  B.   Borderline

  1.   Mucinous cystic tumor with moderate dysplasia

  2.   Intraductal papillary mucinous tumor with moderate dysplasia

  3.   Solid pseudopapillary tumor  C.   Malignant

  1.   Ductal adenocarcinomaxy  2.   Serous/mucinous cystadenocarcinoma (29%)  3.   Intraductal mucinous papillary tumor

Cystic epithelial tumors need to be excluded when patients present with a fluid-containing pancreatic lesion .A variety of cystic neoplasms exist, and include benign serous cystic neoplasms, benign and malignant mucinous cystic neoplasms, and benign and malignant forms of intraductal papillary-mucinous neoplasms IPMNs can present with a dilated pancreatic duct due to the production of mucin by the lesion. At ERCP or upper endoscopy, mucus may be seen extruding from a gaping ampullary orifice. This confirms the presence of an IPMN, and further investigation is warranted to localize the lesion. It is important to not assume that all fluid-filled pancreatic abnormalities represent pseudocysts, or that a dilated pancreatic duct represents only chronic pancreatitis. The presence of a solid component in a cystic lesion, septations within the cyst, and the absence of a clinical history of pancreatitis are factors that should alert the surgeon to the possible presence of a neoplasm. Even in the absence of these factors, presumed pseudocysts should be biopsied at the time of internal drainage to confirm the absence of malignancy, and dilated pancreatic ducts should be biopsied at the time of a decompression procedure to rule out a ductular neoplasm.

Cystic neoplasms with septations and/or irregular nodularity of the cyst wall are more suspicious for malignancy. In an effort to establish a preoperative diagnosis of malignancy, the cyst fluid can be aspirated using EUS and analyzed. Cysts containing viscous fluid with a low amylase content and an elevated carcinoembryonic antigen level are more likely to be malignant. Cytologic examination of the aspirate also can be performed to aid in the diagnosis.

Cystic pancreatic lesions are usually resected if there is any concern regarding malignant potential. Enucleation of small cystic pancreatic neoplasms that are presumed to be benign may be a valid approach; the use of intraoperative ultrasound in such cases is helpful in avoiding injury to the main pancreatic duct and postoperative fistulas. 301 Laparoscopic distal pancreatectomy with or without splenic preservation may be employed for cystic lesions located in the tail of the pancreas. 302 With limited experience worldwide with laparoscopic pancreatic resection, caution is warranted before application of this technique to potentially malignant lesions.

Small cystic lesions in the head of the pancreas present a difficult challenge. Because of the morbidity and mortality risk of pancreaticoduodenectomy, a more conservative operative approach is attractive in a patient with a premalignant lesion such as a mucinous cystadenoma. The duodenum-preserving pancreatic head resections described earlier may offer a safer option when the lesion does not encroach on the duodenum and appears well delineated.

Pseudopapillary and Papillary-Cystic NeoplasmsAn unusual form of exocrine neoplasm occurs predominantly in young women, and is characterized by a large, cystic or partially-cystic appearing lesion which contains frond-like papillary elements on histologic examination. Pseudopapillary and papillary-cystic neoplasms are usually benign, but may assume malignant (metastatic) behavior when they are discovered late in their course. Typically occurring in women from adolescence through the age of menopause, these lesions have been found to express estrogen and progesterone receptors in large numbers. Resection for cure is usually possible despite their typically large size.Pancreatic LymphomaLymphoma can affect the pancreas. Primary involvement of the pancreas with no disease outside the pancreas also occurs. The clinical presentation often is similar to pancreatic adenocarcinoma, with vague abdominal pain and weight loss. Identification of a large mass often involving the head and body of the pancreas should raise suspicion. Percutaneous or EUS-guided biopsy will confirm the diagnosis in most cases. If the diagnosis cannot be confirmed preoperatively, laparoscopic exploration and biopsy is indicated. 303 There is no role for resection in the management of pancreatic lymphoma. Endoscopic stenting to relieve jaundice followed by chemotherapy is the standard treatment, and long-term remission is often achieved.================================================================================================================Surgery Exploration of the Pancreas The entire pancreas must be methodically evaluated. It can be approached by dividing the hepatogastric omentum or the gastrocolic omentum. Under usual circumstances, the gastrocolic omentum is incised widely and provides good exposure of the entire pancreas. If this exposure proves to be inadequate, the hepatogastric omenta can be divided also, and upward traction can be applied to the stomach.Kocherization of the duodenum is necessary for palpation of the head of the pancreas. The hepatic flexure of the colon is mobilized, then the peritoneum is incised lateral to the second part of the duodenum. After completing this step, the left index and middle fingers are placed posterior to the duodenum and the head of the pancreas, with the left thumb anterior. The surgeon can now palpate the head of the pancreas as well as the pancreatic portion of the common bile duct. Lymph nodes can sometimes be felt at the distal portion of the CBD, near the upper part of the posterior surface of the head of the pancreas.The left index finger can continue the exploration posterior to the neck of the pancreas. Occasionally, both index fingers can be used .The surgeon's left hand

approaches the neck from above, the left index finger posterior to the neck. The right hand proceeds from below, the right index finger posterior to the neck.

One criterion for resection for cancer is the ability to separate the neck of the pancreas from the underlying superior mesenteric and portal veins. Silen 66 rejects this maneuver because of possible avulsion of a posterosuperior pancreatoduodenal vein that may enter the superior mesenteric vein on its anterior surface.Papadimitriou et al.219 presented a modificaton of pancreaticoduodenectomy for the treatment of carcinoma of the pancreas and stated the following:Careful detachment of the posterior surface of the pancreas from the anterior surface of the portal vein and performance of pancreaticojejunal anastomosis to a defunctionalized jejunal loop results in lower mortality and morbidity rates, thus making pancreatoduodenectomy a safe procedure.The uncinate process is the most difficult part of the pancreas to explore and evaluate because of its close relation to the superior mesenteric artery and vein.

There are at least six possible routes for abdominal exploration. Each route has particular advantages and disadvantages:220

  1. Through the gastrocolic ligament: route used by most surgeons.2. Through the hepatogastric omentum: useful in patients with exceptionally ptotic stomachs. 3. By detaching the greater omentum from the transverse colon: time consuming, but better visualization of the entire lesser sac. 4. Through the mesocolon: limited exposure of the pancreas, and risks injury to the middle colic blood vessels5. Kocher maneuver: good exposure of the posterior surface of the head of the pancreas.6. Mobilization of the splenic flexure inferiorly and the spleen and tail of the pancreas: appropriate when partial pancreatectomy and splenectomy are

seriously contemplated.

Evaluating ResectabilityWe believe the most appropriate way to evaluate the resectability of a cancerous pancreas is to evaluate the area least likely to be invaded by the neoplasm and proceed to areas most likely to be invaded. Our criteria for resectability are as follows: The surgeon must perform good general exploration of the abdomen with special attention to the pancreas. Attention must be given to specific areas of lymph node drainage that are accessible without further incision, i.e., the pyloric and pancreatoduodenal nodes

and the nodes at the root of the mesentery (Fig. 21-44A). Further investigation of lymph nodes is necessary. This requires some incision of the hepatogastric omenta and a Kocher maneuver. Pancreatoduodenal,

celiac, and left gastric nodes, together with nodes of the superior and inferior pancreatic borders, should be inspected. Once the diagnosis of cancer has been determined and the previously outlined exploration has indicated a resectable lesion, the following final steps should

be undertaken before the start of the actual resection.

→ Further exploration of the area of the ligament of Treitz to ensure mobility of the fourth part of the duodenum and the first portion of the jejunum.→ Evaluation of the posterior surface of the head of the pancreas and the distal common bile duct. Ensure there is no fixation to underlying structures, including the

inferior vena cava.→ Gentle examination of the uncinate process and elevation of the neck of the pancreas with one or two fingers. Ensure they are not fixed to the superior mesenteric

vessels or to the portal vein (see Fig. 21-56). Cattell and Warren221 recommend incision of the hepatogastric ligament with division of the right gastric and gastroduodenal arteries to ensure adequate evaluation of possible fixation in this region.

→ Final review of the local anatomy to identify any previously undetected vascular anomalies. Any available angiograms should be studied.

Complications of Pancreaticoduodenectomy

The most common causes of death are sepsis, hemorrhage, and cardiovascular events.

Postoperative complications are unfortunately still very common, and include

Delayed gastric emptying is common after pancreaticoduodenectomy and is treated conservatively as long as complete gastric outlet obstruction is ruled out by a contrast study

Pancreatic fistula

Hemorrhage can occur either intraoperatively or postoperatively.Intraoperative hemorrhage typically occurs during the dissection of the portal vein. A major laceration of the portal vein can occur at a point in the operation at which the portal vein is not yet exposed. Temporary control of hemorrhage is generally possible in this situation by compressing the portal vein and superior mesenteric vein against the tumor with the surgeon's left hand behind the head of the pancreas. An experienced assistant is needed to divide the neck of the pancreas to the left of the portal vein and achieve proximal and distal control. Sometimes the vein can be sutured closed with minimal narrowing. Other times, a patch repair or segmental resection and interposition graft may be needed

Postoperative hemorrhage can occur from inadequate ligature of any one of numerous blood vessels during the procedure. Hemorrhage can also occur due to digestion of retroperitoneal blood vessels due to a combined biliary-pancreatic leak. Uncommonly, a stress ulcer, or later a marginal ulcer, can result in gastrointestinal hemorrhage.

1. Pancreatoenteric anastomosis (the least secure anastomosis)

Leakage or disruption with:

  a. Abscess or peritonitis

  b. Ileus

  c. Pancreatic fistula

  d. Wound infection and dehiscence

  e. Bleeding from erosion of large vessels (Gadacz et al., 1978)

  f. Ductal fibrosis, obstruction, and pancreatitis

3. Inadequate gastric resection

Gastrojejunal ulceration (anastomotic ulcer)

4. General Operating room hemorrhage from major vessels:

  a. Portal vein

  b. Hepatic artery, normal or aberrant

  c. Superior mesenteric artery or vein

  d. Splenic artery or vein

  e. Inferior vena cava

  f. Renal arteries or veins

  g. Middle colic artery

Acute postoperative pancreatitis with:

  a. Ductal obstruction

  b. Direct injury to pancreas with leakage from pancreatic parenchyma

  c. Interference with blood supply or drainage

Procedure Complications

)

2. Biliary-enteric anastomosis (the most secure anastomosis)

Leakage or disruption with:

  a. Abscess or bile peritonitis

  b. Biliary obstruction

  c. Biliary fistula

  d. Obstruction at the anastomotic site

  e. Ascending or descending cholangitis