Pancreatic Cancer

Epidemiology

Pancreatic cancer has a 5% annual incidence and causes about 5% of all cancer deaths. It is the 4th leading cause of cancer death in both women and men

In Romania in 1996 the incidence was 6 per 100,000 inhabitants, and the mortality rate of 9 per 100,000.

In Romania the estimated incidence for 2000 was 8.86 per 100,000 and 8.32 deaths per 100,000 inhabitants.

Risk factors:

1. Smoking is the only identified risk factor. About 30% of pancreatic cancers are attributable to smoking. Smokers develop the disease 2-3 times more often than non-smokers.

2. Coffee and alcohol consumption is unlikely to constitute risk factors for pancreatic cancer

3. A diet rich in fat. There is a strong correlation between body fat and abdominal and pancreatic cancer. Foods that have a high content of folates have a protective role.

4. Partial gastrectomy

5. Chronic pancreatitis

6. Type II Diabetes increases the risk of pancreatic cancer by about 50%, and studies have found a positive correlation between obesity and pancreatic cancer.

7. Hereditary. Pancreatic cancer risk is increased (18 times) in families that first-degree relatives have pancreatic cancer.

Histological Types:

75% of the tumors are located in the head of the pancreas.

38% of tumors are multi-centric.

The histological classification of malignant tumors of pancreatic

I. Malignant:

Cell of origin:

Duct:

1. Ductal Adenocarcinoma – 82%

2. Large cell carcinoma (giant) – 5%

3. Cystadenocarcinoma – rare

4. Mucinous carcinoma – rare

5. Small cell carcinoma – rare

Acinar:

1. Acinar cell carcinoma 13%

2. Acinar cell cystadenocarcinoma

Connective tissue:

1. Sarcomas

2. Lymphomas

II. With uncertain malignant potential:

1. Intraductal papillary mucinous tumor

2. Mucinous cystadenoma

3. Cystic papillary neoplasm

III. Metastatic Tumors

The autopsy showed that the ratio of primary pancreatic tumor and metastatic pancreatic tumor is 1/4. The tumors that metastasize most commonly in the pancreas are: breast, lung, malignant melanoma and cutaneous non-Hodgkin lymphoma.

Tumor markers

CA 19-9 tumor marker most studied associated it with pancreatic cancer. The normal values ​​are <35 IU / ml. High values ​​of C.A19-9 support pancreatic cancer diagnosis but are not specific to it. The resected pancreatic cancer CA 19-9 level decreased. CA 19-9 has little value in the diagnosis and staging.

Signs and symptoms: abdominal pain, jaundice, anorexia, weight loss, nausea, palpable gallbladder (Courvoisier sign). Signs of advanced disease: superficial migratory thrombophlebitis, left supraclavicular lymphadenopathy, periumbilical tumor mass.

Paraneoplastic syndromes:

1. Panniculitis syndrome, arthritis, eosinophilia

2. Dermatomyositis, polymyositis

3. Deep vein thrombosis recurrent idiopathic

4. Cushing’s syndrome

Percutaneous aspiration cytology

Cytological diagnosis based on fine needle aspiration of the pancreas is a safe process with a sensitivity of 57-96%. The rate of complications is low but can occur seeding along the needle tract and intraperitoneal seeding rate is increased. The process should be avoided in patients with apparently resectable lesions.

Diagnosis and staging is done by:

• history, clinical examination,

• abdominal ultrasonography, abdominal C.T,

• cholangiopancreatography endoscopic retrograde,

• tumor markers,

• endoscopic ultrasonography

• fine needle tumor puncture in inoperable patients.

The diagnosis is confirmed by histopathology.

see table no. TNM staging 20 exocrine pancreas tumors

Primary Tumor (T)

Tx- primary tumor cannot be assessed

T0- no evidence of primary tumor

Tis- carcinoma in situ

T1 tumor limited to the pancreas with the largest diameter ≤2 cm

T2 tumor limited to the pancreas with the largest diameter> 2

T3- tumor extended directly to one of the following bodies duodenum, biliary, pancreatic tissue

T4- Tumor extends directly to one of the following organs: stomach, spleen, colon, adjacent large vessels

Regional lymph nodes (N)

Nx- regional lymph nodes cannot be assessed

N0- no regional lymph node metastasis

Regional lymph node metastases N1-

N1a- metastases in a single regional lymph node

N1b- metastases in regional lymph nodes

Distant metastasis (M)

MX distant metastasis cannot be assessed

M0- no distant metastases

M1 distant metastasis

Stages:

St. Tis N0 M0 0

St. T1-2 N0 M0 I

St.II T3 N0 M0

T1-3 N1 M0 St.III

St.IVa T4 any N M0

St.IVb any T any N M1

Clinical staging (radiological) pancreatic cancer

Stage I: resectable disease (T1-3, T4a selected cases, Nx, Mo)

-There is evidence of tumor extension to the celiac axis or superior mesenteric artery

-confluence of  portal vein or superior mesenteric

-There is no extrapancreatic disease

Stage II: Disease locally advanced (T1-4, Nx-1, Mo)

-arterial invasion(celiac axis or superior mesenteric artery) or

– vein occlusion(portal vein, superior mesenteric vein)

-there is no extrapancreatic disease

Stage III metastatic disease (T1-4, Nx-1, M1) to the liver, peritoneum and rarely lung

TREATMENT

Therapeutic Indication

Most patients with pancreatic cancer have locally advanced disease or metastatic disease. Only 5-20% of patients have resectable disease.

Recommended diagnostic evaluation for a patient with pancreatic head cancer is based on three principles:

1. Laparotomy must be therapeutic rather than diagnostic.

If the primary tumor cannot be resected completely (pancreas – duodenectomy) there is no survival advantage for the patient. In contrast with colon cancer or gastric there is no advantage for palliative resection (with positive margins) pancreatic cancer.

Only 30-60% of patients operated were completely resected.

2. Resecability will be determined preoperatively.

There is a misconception in pancreatic cancer, as resectability is best determined intraoperatively.

Laparotomized median survival of patients was 6 months so complete preoperative assessment is required by abdominal CT, angiography and laparoscopy. If one of these procedures indicates invasion or dissemination mesenteric local or regional resectability rate is 5%, while if all are negative resectability rate is 78%.

Criteria C. T. The resectability are:

a) The absence of extrapancreatic disease

b) An obvious confluence of the superior mesenteric vein portal vein.

c) there is no extension of the tumor in celiac axis or superior mesenteric artery.

3. Palliative laparotomy should be avoided when possible.

In patients with locally advanced or metastatic Palliative surgery is rarely necessary.

In patients whose survival is expected to be less than 6 months with rapidly progressive disease with liver metastases, ascites, it recommended placement of “stents” (limiting Endoscopic beds) that maintain biliary permeability.

In patients with good performance status, with nonmetastatic locally advanced disease biliary surgery is recommended.

I. localized resectable disease

It is recommended that pancreatic-duodenal resection (Whipple procedure) or Shiu modification of it be performed. Resect in large the distal portion of the stomach, duodenum, jejunum, the first portion of the head and body of the pancreas. Terminolateral bile anastomoses with jejunum is outstanding, and the remaining pancreas jejunum anastomoses with outstanding gastrojejunostomy and vagotomy.

Postoperative radiotherapy plus chemotherapy is recommended by 5 FUR.

The total dose of 40-60 Gy in the irradiation of 1.8-2 Gy fractions daily.

5 fluorouracil is administered 500 mg / m2 / day x 3 days iv 1 cycle every 4 weeks during the irradiation, and weekly thereafter 500 mg / m2 / z for 6 months.

II. Localized unresectable disease

I is recommended surgical biliary bypass (colecistojejunostomy or coledocojejunostomy). The mortality rate is 20% and average survival is 20%.

Jaundice can be improved by placing endoscopic tube limiters (stents) with 1-2% reduction in mortality and length of stay. No differences in survival between patients treated endoscopically operate and the limiting tubes (stents).

a) After solving the biliary obstruction is recommended 40-60 Gy local radiotherapy associated with chemotherapy 5-FU or gemcitabine.

b) intraoperative radiation therapy or radioactive sources in tumor Intraosteal is another therapeutic modality that relieves pain and increases the median survival in 50-90% of patients.

Chemotherapy with Gemcitabine II 1000 mg / m2 IV in 30 minutes,

Weeks, 3 weeks, 28 days,

Chemotherapy

Adjuvant chemotherapy has proved beneficial in patients treated with gemcitabine versus symptomatic treatment. Pancreatic resected cancer patients treated with gemcitabine, DFS and OS were improved.

Chemotherapy is used in neoadjuvant situation, adjuvant in locally advanced disease and metastatic disease.

III. Advanced metastatic disease

In patients with extensive metastatic disease, severe pain, debilitating condition marked, chemotherapy is less indicated toxic effects of chemotherapy causing additional complications. In patients with good performance status chemotherapy is recommended.

Monochemotherapy

1. Gemcitabine 1000 mg / m2 IV in 30 minutes,

Weeks, 3 weeks, 28 days (category I)

2. Capecitabine 1250 mg po x 2 / day for 14 days

Repeat in 3 weeks (CAT IIIB)

Combinations of chemotherapy

1. Gemcitabine 1000 mg / m2 IV weekly for 30 minutes, 3 weeks, 28 days (category I)

Erlotinib 100mg / day po daily

2. FOLFIRINOX

Irinotecan 165 mg / m 2 IV / day, Day 1

Oxalipaltin 85mg / m2 IV day 1

Leucovorin 400mg.m2 IV day 1

5 FU 3200mg / m2 IV continuous infusion day 1.2

Repeat 14 days (category I), maximum 14 cycles

3. Gemcitabine 1000 mg / m2 IV weekly for 30 minutes, 3 weeks, 28 days (category I)

Capecitabine 830mg / m 2 x 2 / day

Repeat at 54 weeks

4. Patients with possible hereditary cancer

Gemcitabine 1000 mg / m2 IV on day 1 and 8 in 30 minutes

Cisplatin 25 mg / m2 day 1 and 8 to 30 minutes

Repeat 21 days 8 cycles or until disease progression

Regional chemotherapy through the catheter inserted into the hepatic artery. It is indicated in patients operated with pancreas-duodenectomy and there are only liver metastases. The 5 FUR used was 125 mg / day for 4-5 weeks postoperatively. The survival rate at 5 years was 39%.

Treatment of pain. Abdominal pain is the most common symptom seen in patients with pancreatic cancer. Treatment consists of: non-opioid analgesics, opioids, spinal analgesia and neurolitic procedures.

Pancreatic cachexia. Megestrol acetate is recommended 400-800 mg / day may be an effective appetite stimulant.

Prognostic

1. Stage of disease. Median survival depending on the stage of the disease:

a stg.I-17 months

a stg.II -10 months,

a stg.III -12 months,

a stg.IV -6 months.

2. node invasion. Patients with uninvaded lymph nodes have a better prognosis that those with nodal invasion.

3. small and well differentiated tumors have a good prognosis.

4. Type of resection. In patients who did not undergo resection survival at 5 years was 0%, and those who have received was 24%.

5. In patients with unresectable favorable prognostic factors are: good performance status (ECOG 0,1,2) and absence of symptoms.

Survival of patients

Survival at 5 years was:

– 26% for those with negative resection margins.

– 8% in those with positive resection margins.

– 36% for those with node-negative.

– 5% in patients with node-positive

Tracking patients is made by clinical examination, liver function tests, abdominal ultrasound, CA19-9 (if increased diagnosis) every 3 months during the first 2 years and then every 6 months. CXR and C. T. abdominal recommended every 12 months.