Diseases of the pancreas Dept. of General and Transplant Surgery Diseases of the pancreas Jakub Szmytkowski

Anatomy - location Retroperitoneal (except part of the tail) in the epigastrium and left infracostal region Approximate dimensions: L 15 cm, W 3-4 cm, T 1-2 cm; weight 60-100 g

Anatomy - parts head Isthmus (notch) uncinate process body tail

Pancreatic ducts The pancreatic duct, or duct of Wirsung (also, the major pancreatic duct)  a duct joining the pancreas to the common bile duct to supply pancreatic juices which aid in digestion provided by the "exocrine pancreas". The pancreatic duct joins the common bile duct just prior to the ampulla of Vater, after which both ducts perforate the medial side of the second portion of the duodenum at the major duodenal papilla.

Pancreatic ducts Accessory pancreatic duct (duct of Santorini) connects straight to the duodenum at the minor duodenal papilla In some cases, the main pancreatic duct is smaller than the accessory pancreatic duct and the two may not be connected. In such people, the accessory duct carries most of the pancreatic juice.

Pancreatic duct

Anatomical relations anterior: transverse colon (head) pylorus (body) posterior: VCI, CBD, aorta, superior mesenteric a., renal veins left: splenic hilus, splenic flexure right: duodenum superior: celiac trunk, splenic a.

Surgical diseases of the pancreas Acute pancreatitis Chronic pancreatitis Cysts Tumors

Goals of pancreatic surgery Completion of diagnosis Treatment of pancreatitis Treatment of infection and complications Pain control Malignant tumors curative palliative Management of endocrine disorders

Acute pancreatitis Acute pancreatitis is a complex disorder of the exocrine part of the pancreas. Its exact patomechanism has not been fully explained, but can be described as acute injury to the acinar cells with a local and generalized inflammatory response. Overall mortality 6.0-20.5% Necrotizing – hemorrhagic (5 – 15%) 50+% Morbidity (Poland) 240 / 100 000 / year No specific therapy

Types interstitial edematous pancreatitis sterile necrotizing pancreatitis infected pancreatic necrosis/abscess hemorrhagic pancreatitis

Frequent causes 80% gallstones alcohol idiopathic hyperlipidemia hypercalcemia drugs and toxins ( steroids, immunosuppressants: Azathioprine, Thiazide, Valproic acid, Tetracycline, and Trimethoprim-sulfamethoxazole ) endoscopic retrograde cholangiopancreatography trauma surgery 80%

Less frequent causes Malignancies of the ampulla of Vater Pancreatic carcinoma Diverticulum of the duodenum Vasculitis

Even less frequent causes infection: viral (Coxsackie, mumps , HIV), parasites Autoimmune disorders: lupus, Sjögren’s syndrome alpha1-antitripsin deficiency Anorexia Repeated marathon running Scorpion venom Pancreas divisum

Physiology The pancreas secretes 500-800 ml/ day of transparent, anodorous, isoosmotic juice with a high pH, containing bicarbonates and digestive enzymes Stimulants: secretin, duodenal pH <4.0 Cholinergic stimulation – vagus nerve

Physiology The proportions of different enzymes differ; various nutrients stimulate the secretion of various enzymes Cholecystokinin (CCK) i s the primary regulator Secondary mediators include Ca++ and diacylglycerol

Pancreatic enzymes Inhibitors: Amylase Active Proteases ( trypsin) Inactive Lipases Inactive Inhibitors: Alpha 1-antitrypsin Beta 2-macroglobulin Pancreatic secretory trypsin inhibitor (PSTI)

Pathology overpressure in Wirsung’s duct abnormal inhibition of secretion of zymogens and inappropriate activation of pancreatic zymogens inside the pancreas, most notably trypsinogen during an acute pancreatitis episode there is colocalization of lysosomal enzymes, specifically cathepsin, with trypsinogen. Cathepsin activates trypsinogen to trypsin leading to further activation of other molecules of trypsinogen and immediate pancreatic cell death according to either the necrosis or apoptosis mechanism (or a mix between the two)

Pathology an extensive inflammatory response due to pancreatic cells synthesizing and secreting inflammatory mediators: primarily TNF-alpha and IL-1 inflammatory response leads to the secondary manifestations of pancreatitis: hypovolemia from capillary permeability, acute respiratory distress syndrome, disseminated intravascular coagulations, renal failure, cardiovascular failure, and gastrointestinal hemorrhage

Physiology

Pathology

Signs and symptoms SEVERE abdominal pain – usually (95-100%) first symptom, often radiates to the back Nausea,vomiting without relief ( 80%) Fever (onset crucial for correct management: 1st week – SIRS; 2 weeks and later – necrosis infection) Epigastric tenderness Peristaltic sounds weak or absent (paralytic ileus)

Signs and symptoms Tender epigastric mass – parapancreatic infiltration Shock Pancreatic encephalopathy Tachycardia (often) Hypotonia (due to hypovolemia) Jaundice – (20-30%)

Rare sypmtoms Kamenchik's sign (pain with pressure under the xiphoid process) Mayo-Robson's sign (pain while pressing at the top of the angle lateral to the Erector spinae muscles and below the left 12th rib (left costovertebral angle (CVA)) Loeffler’s sign – facial erythema Clairmont’s sign – left pleural effusion Körte's sign (pain or resistance in the zone where the head of pancreas is located (in epigastrium, 6–7 cm above the umbilicus))

Grey Turner's sign bruising of the flanks, appearing as a blue discoloration a sign of retroperitoneal hemorrhage Also seen in: Blunt abdominal trauma Ruptured abdominal aortic aneurysm Ruptured / hemorrhagic ectopic pregnancy

Cullen's sign superficial edema and bruising in the subcutaneous fatty tissue around the umbilicus

Fox’s sign bruising along inguinal ligament

Symptoms - summary All of them non -specific Abdominal pain 85-100% Nausea and vomiting 55-90% Anorexia 80% Tachycardia 65-80% Fever 12-80% Bowel obstruction 50-80% Tender abdominal mass 90-99% All of them non -specific Baron TH, Morgan DE. Acute Necrotizing Pancreatitis, NEJM, 1999

Lab results indicative of AP Elevated serum amylase and lipase levels  no role in assessing disease severity. Serum lipase rises 4 to 8 hours from the onset of symptoms and normalizes within 7 to 14 days after treatment Serum amylase may be normal (in 10% of cases) for cases of acute or chronic pancreatitis (depleted acinar cell mass) and hypertriglyceridemia. Reasons for false positive elevated serum amylase include salivary gland disease (elevated salivary amylase), bowel obstruction, infarction, cholecystitis, and a perforated ulcer. If the lipase level is about 2.5 to 3 times that of amylase, it is an indication of pancreatitis due to alcohol Decreased serum calcium Glycosuria Increased CRP

Acute pancreatitis: US imaging Abdominal US usually performed  pancreas often invisible (intestinal gasses, obesity) US in acute pancreatitis: pancreas enlarged, boundaries not clearly defined (inflammatory infiltration), heterogenous echogenicity US important for ID of causative factor (gallstones) Monitoring of complications (abcess, cyst, necrosis)

US

Computed tomography „Gold standard” in AP imaging; enables assessment of severity and necrotic changes (Balthasar score A-E) Helps assess severity (CTSI index) Recommended after 72 h from onset of symptoms, In critical patients – immediate CT Further scans after 7-10 days or upon significant changes of patient’s condition

Balthasar score Balthazar Grade Appearance on CT CT Grade Points Normal CT 0 points Grade B Focal or diffuse enlargement of the pancreas 1 point Grade C Pancreatic gland abnormalities and peripancreatic inflammation 2 points Grade D Fluid collection in a single location 3 points Grade E Two or more fluid collections and / or gas bubbles in or adjacent to pancreas 4 points

Necrosis score CTSI score = Balthasar + necrosis score Necrosis Percentage Points No necrosis 0 points 0 to 30% necrosis 2 points 30 to 50% necrosis 4 points Over 50% necrosis 6 points CTSI score = Balthasar + necrosis score

CT scan of AP patient

Other imaging modalities Chest X-ray Interstital atelectasis, pleural effusion, ARDS Abdominal X-ray Fluid levels, bowel distension (signs of paralytic ileus) MR  indication for imaging of patients with an allergy to CT's contrast material

Course of the disease Edematous AP (60-70%) of the patients – treatment of symptoms, no complications, mortality < 1% Severe AP (30-40% )– mortality between 10% (sterile necrosis) and 25% (infected necrosis); if organ – specific complications arise, the mortality rates increase to 20% and 50-80% , respectively. in severe AP there are two periods of increased mortality: early (~60% deaths) – first 7-14 days: early MOF, severe ARDS due to SIRS late (~40% deaths) – 3-4 weeks from onset  infection of necrotic tissues, abscess formation  sepsis  septic shock  MOF

AP severity scores Ranson criteria for non – gallstone AP At admission: Age in years > 55 years White blood cell count > 16000 cells/mm3 Blood glucose > 10 mmol/L (> 200 mg/dL) Serum AST > 250 IU/L Serum LDH > 350 IU/L

After 48 hrs Serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit fall > 10% Oxygen (hypoxemia PO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L

Ranson for gallstone AP At admission: Age in years > 70 years White blood cell count > 18000 cells/mm3 Blood glucose > 12.2 mmol/L (> 220 mg/dL) Serum AST > 250 IU/L Serum LDH > 400 IU/L

After 48 hrs Calcium (serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit fall > 10% Oxygen (hypoxemia PO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 5 mEq/L Sequestration of fluids > 4 L

Ranson - interpretation If the score ≥ 3, severe pancreatitis likely. If the score < 3, severe pancreatitis is unlikely Or: Score 0 to 2 : 2% mortality Score 3 to 4 : 15% mortality Score 5 to 6 : 40% mortality Score 7 to 8 : 100% mortality

Conservative treatment Anti –shock treatment Pain control Nil-by-mouth regime Nasogastric tube placement Total parenteral nutrition Stress ulcer prevention Wide - spectrum antimicrobial Fluid replacement therapy

Endoscopic retrograde cholangiopancreatography (ERCP)  combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems plastic catheter inserted through the ampulla, and radiocontrast is injected into the bile ducts and/or pancreatic duct. Fluoroscopy is used to look for blockages, or other lesions such as stones

ERCP opening of the ampulla can be enlarged (sphincterotomy) with an electrified wire (sphincterotome) and access into the bile duct obtained  trawling of the common bile duct with a basket or balloon to remove gallstones and the insertion of a plastic stent to assist the drainage of bile direct electrohydraulic lithotripsy

ERCP

Indications for surgery Diagnosis uncertain( peritoneal signs) Symptoms of necrosis infection or abscess Complications: bowel necrosis, perforation, hemorrhage

Timing of surgery Almost never before 10th day after onset – unless fulminating necrosis occurs surgery 0 – 7th day - mortality 38% surgery 8 – 14th day - mortality 28% surgery >21 day - mortality. 15% Complete necrosis facilitates removal

The role of surgery in severe AP Necrectomy, lavage / drainage of the bursa omentalis laparostomy abscess drainage debridement of the retroperitoneal space

Video – Assisted Retroperitoneal Debridement (VARD)

Chronic pancreatitis Long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. Damage is non – reversible.

Causes Alcohol Smoking Malnutrition Hereditary Trypsinogen and inhibitory protein defects Cystic fibrosis Idiopathic (unknown) Trauma Hypercalcemia

Forms Calcifying chronic pancreatitis – alcohol Proteins present within the pancreatic juice precipitate  secondary calcification

Chronic pancreatitis Chronic obstruction of pancreatic juice flow may lead to chronic pancreatitis (tumors, gallstones, pancreas divisum, scarrring)

Signs & symptoms pain – severe postprandial pain in the epigastrium, radiating to the left epigastrium or back; due to increase in intraductal pressure and / or inadequate blood supply Weight loss & cachexia (loss of exocrine function, fear of pain after eating) fatty diarrhea (steatorrhea) dyspepsia jaundice

Complications diabetes abscess cyst duodenal obstruction biliary tree obstruction

US pancreas enlarged hypoechogenous distended Wirsung’s duct calcifications within parenchyma, stones within Wirsung’s duct pseudocysts

Conservative treatment Dietary fat limited to 100 gram / d Replacement pancreatic enzymes Pain control Parenteral nutrition in severe cachexia Insulin

Indications for surgery Debilitating pain nonresponsive to medical treatment Duodenal obstruction Ascites or pleural effusion Suspected malignancy Cysts, fistulae

Surgical treatment Puestow procedure

Surgical treatment anastomoses gastrointestinal biliary

Endoscopic treatment

Palliative treatment neurolysis

Pancreatic cysts Pseudocysts (no epithelium) > 75% Secondary to inflammation, trauma True cysts – rare, usually in polycystic syndromes

Clinical presentation Usually asymptomatic, present as abdominal mass Serum amylase usually normal

Imaging

Complications infection hemorrhage Fistula external internal

Treatment Internal drainage Jurasz procedure

Treatment Percutaneous drainage

Tumors 90% - ductal adenocarcinoma Neuroendocrine tumors (insulinoma, glukagonoma, vip-oma, gastrinoma etc.) 1% - benign cystic tumors (serous, mucous cysts)

Pancreatic cancer Morbidity 10/ 100.000 / year ♂ 30% more likely 3rd most frequent malignancy of the alimentary tract More frequent after 60 years of age 3% of all malignancies 80% preceded by diabetes

Risk factors smoking alcohol abuse chronic pancreatitis (linked but not causal) diet: fat + red meat, soft drinks genes (BRCA-2) increased BMI

Location Head 60-70% Body 15-20% Tail 5% More than one part 20%

Signs and symptoms Late, non - specific Weight loss -90% Pain -75% Anorexia -60% Malnutrition -75% Hepatomegaly -65% Skin itch -40% Courvoisier’s sign -30% Diabetes -15% Abdominal tenderness -20% Palpable abdominal mass-10% Ascites -5% Jaundice -6%

Diagnosis CT ECPW EUS Diagnostic laparoscopy  laparoscopic US Marker : CA 19-9

Prognosis 5 – year survival  approx. 5% Tumor limited to pancreas, resectable – expected survival 17 months Locally advanced tumor, non-resectable – mean expected survival 8-9 months Metastases – mean expected survival 4-6 months 5 – year survival  approx. 5%

Treatment radical: resection + radiotherapy + chemotherapy palliative: fecal diversion, stenting, brachytherapy

Surgical treatment Whipple procedure – en bloc removal of the distal segment (antrum) of the stomach; the first and second portions of the duodenum; the head of the pancreas; the common bile duct; and the gallbladder

Longmire – Traverso ( resection of the head of the pancreas, preserving the pylorus)

Pancreatic tail resection (usually with splenectomy)