Pancreatic Carcinoma

  • Risk factors:
  •             – Smoking
  •             – Alcohol
  •             – Chronic pancreatitis: 4% risk of developing pancreatic cancer within 20 years
  •             – Hereditary (<10% pancreatic cancer has hereditary etiology): hereditary chronic pancreatitis
  •             – Family cancer syndromes:
  •                      > Peutz-jeghers syndrome
  •                      > HNPCC
  •                      > Von-Hippel Lindau syndrome
  •                      > Ataxia telangiectasia
  • Other risk factors:
  •              – Gall bladder stone
  •             – DM: Highest risk for those with a duration of 2-8 years. Use of GLP-1 analogue (Exenatide), DPP4 inhibitors (Sitagliptin) cause 3 fold increased risk of pancreatic carcinoma
  •             – High intake of animal fat
  •             – Prolonged contact with petroleum and wood pulp
  • 5 year survival rate:
  •             – 23% for patients with localized disease
  •             – 2% for distant disease
  • Incidence:
  •             – Rarely seen before the age 45 years
  •             – Incidence sharply rise after the age 50 years
  •            – Slightly male predominant disease
  •            – More common in blacks

  • Pathology
  • – > 95% of malignant neoplasm of pancreas arise from the exocrine elements of the gland (Duct + Acinar cell) and features consistent with adenocarcinoma
  • – 85-90% of pancreatic carcinoma are ductal adenocarcinoma
  •                 * 60- 70% in the head of the gland
  •                 * 5- 10% in body
  •                 * 10-15% in tail region
  • Tumor in the head of the gland causes
  •              > Distal bile duct obstruction ………..>Jaundice
  •              > Pancreatic duct obstruction…………> Obstructive pancreatitis
  • – Pancreatic pathologic changes
  •               > PD dilatation
  •               >Fibrous atrophy of parenchyma
  • – Extrapancreatic extension into retroperitoneal tissue
  •              > Results in invasion of the portal vein, sup. mesenteric vein & nerves
  • – Neoplasm in tail do not cause biliary/ pancreatic duct obstruction
  • Clinical features:
  • – Most patients present with unresectable mass or metastatic disease
  • – Tumors in head region produce symptoms earlier
  • – Tumors of the distal gland are characterized by their ‘silent’ presentation, physical findings appear only after extensive local growth or wide metastasis
  • Jaundice: Palpable GB (Courvisier’s law) present in <1/3rd patients
  • – Abdominal pain: Low intensity, dull, vaguely localized to upper abdomen, may be localized to middle and upper back. It may be postprandial and lead to reduce caloric intake. Severe pain is more common with tumor involving body and tail
  • – Steatorrhea, malabsorption due to pancreatic exocrine insufficiency
  • – DM, pancreatitis of varying severity
  • – New onset DM may herald Ca. pancreas in 1/4th patients over 50 years
  • – Acute pancreatitis is uncommon initial presentation
  • – Others: Nausea, anorexia, wt. loss may or may not be due to partial duodenal obstruction

Investigations:

USG and CT scan

  • – USG useful to evaluate gall stone and biliary dilatation
  • – CT is the Investigation of choice for diagnosis and staging
  • – Pancreatic protocol
  •          > Consists of dual-phase scanning and oral contrast
  •          >First phase (arterial phase)
  •                  1.Obtained 40 seconds after IV contrast injection
  •                  2.Neoplastic lesion is non enhanced
  •                  3. Maximum enhancement of normal pancreas occur in this phase
  •           > Second phase (Portal venous phase)
  •                  1.Obtained 70 seconds after IV contrast injection
  •                  2.Allows identification of liver metastasis, assessment of portal/ mesenteric vein involvement
  • CT criteria for unresectability
  •             – Distant metastasis (liver, peritoneum, other sites)
  •             – Encasement of celiac axis or other sites
  •             – Portal vein, sup. mesenteric vein occlusion

** 5-15% of patients predicted to have resectable disease according to CT criteria are found at laparoscopy to have unresectable lesion

 

EUS:

  • – Most sensitive method for detecting small tumors
  • – EUS-FNAC enhances accuracy of diagnosis
  • – Not necessary for all patients
  • – Provides no information regarding metastatic disease, complementary CT/MRI necessary for complete pretreatment staging

 

   Tumor Marker:

  • – CA-19-9: Cut –off value 37u/ml (sensitivity, specificity >85%)

                           Figure: Diagnostic algorithm for pancreatic carcinoma

  • TNM staging of pancreatic carcinoma

              – T1: Tumor limited to the pancreas, <2 cm in diameter

             – T2: Tumor limited to the pancreas, >2 cm in diameter

             – T3: Tumor extends beyond the pancreas but without involvement of the celiac axis or the

        Sup. Mesenteric artery

            – T4: Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary

         tumor)

                                Lymph node metastasis

                      – N0: No regional LN metastasis

                      – N1: Regional LN metastasis

 

 

Treatment of Pancreatic Carcinoma

  • SURGERY:
  • Absolute contraindication for surgery:
  •              – Ascites
  •              – Metastasis to liver, peritoneum, Periaortic LN
  • Relative contraindication for surgery:
  •              – Encasement or occlusion of superior mesenteric vein or portal vein
  •              – Direct extension of the disease to celiac axis, superior mesenteric artery, vena cava, aorta
  • Routine preoperative ERCP with biliary stenting to relieve jaundice
  •              – Not recommended
  •              – It increase the surgical infectious complications
  • Candidates for preoperative ERCP with biliary stenting
  •               – Patients with deep jaundice and expected delay in curative surgery
  •               – Patients with jaundice entering preoperative (neoadjuvant) therapy
  •               – As palliative measure:
  •                        > Frail patients to withstand an operation
  •                        > Unresectable disease
  • SURGICAL OPTIONS FOR RESECTABLE DISEASE  

1.Pancreticoduodenectomy (Whipple procedure/ Modified Whipple procedure):

  • – Done for Ca head of pancreas
  • – After the procedure most patients receive adjuvant chemotherapy with Gemcitabin and possibly radiation therapy
  • – Pancreatic fistula is the most common complication of Whipple procedure in patients with small pancreatic duct and/or anatomically soft pancreas
  • – Only 15% patients are candidates for pancreatectomy
  • – Mortality rate is only 1-3% at centres that performs large number of this operation
  • 5 year survival after Whipple procedure:
  •                 * 10% for node positive disease
  •                 * 25-30% for node negative disease
  • Factors associated with improved survival after whipple procedure:
  •                 # Tumor size <3cm
  •                 # Well-differentiated tumor
  •                 # Negative surgical margin
  •                # Absence of LN metastasis

2.Distal pancreatectomy with splenectomy:

  • – For tumor located in body and tail of the pancreas

3.Total pancreatectomy:

  • – For IPMN, pancreatic endocrine tumor

Figure:  Pancreaticodudenectomy operation

 

  • NEOADJUVANT THERAPY:

 

  • – Still investigational
  • – Argument against neoadjuvant therapy: Cancer progression during therapy may convert potentially curative, resectable disease into an unresectable terminal cancer

 

  • TREATMENT FOR LOCALLY ADVANCED DISEASE
  • – Optimal treatment is controversial
  • – Combination chemotherapy and radiotherapy causes modest improvement of survival
  •          Prognosis:
  • – Poor even after curative surgery
  • – 5 year survival after surgery 25% with a median survival 12-24 months
  • Risk factors for recurrent disease:
  •          – Positive margin
  •          – Lymph node involvement
  •          – High grade tumor
  •         – Primary tumor size >2.5 cm

** Pancreatic cancer most commonly recur with distant metastatic disease

** Only 15% recurrence is isolated to local tumor bed

 

  •  
    • PALLIATIVE TREATMENT:
  • – Palliative chemotherapy: FOLFIRINOX for metastatic disease is superior to Gemcitabine alone.5-FU, leucovorin, oxaliplatin, irinotecan
  • A. Palliative endoscopic procedures:
  • 1.Biliary stenting:  
  • Plastic stent for short term use and require exchange every 3 months to prevent complications from stent occlusion or cholangitis
  • – Metallic stents: Covered, Uncovered
  •  2.Duodenal stenting:
  • – To relieve duodenal obstruction
  •  3.Celiac plexus block/neurolysis:
  • – By EUS guidance, percutaneous, laparoscopically
  • – Thoracic splanchniectomy is an alternative approach to interrupt pain
  • B.Percutaneous biliary drainage:
  •     – If endoscopic drainage is not possible
  • C.Palliative surgical procedures
  •     – Gastrojejunostomy to alleviate duodenal obstruction
  •      – Celiac plexus block for pain control

 

 


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