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Pancreatic Cancer: Risk Factors, Clinical Features, Diagnosis, Treatment, Neuroendocrine Tumors of Pancreas

Jun 29, 2023

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Risk Factors of Pancreatic Cancer

Causes of Pancreatic Cancer

Symptoms of Pancreatic Cancer

Diagnosis

Radiological Signs

Treatment of Pancreatic Cancer

Neuroendocrine Tumors (Net) of Pancreas

Diagnosis

Insulinoma

Clinical Features of Insulinoma

Diagnosis of Insulinoma

Treatment of Insulinoma

Gastrinoma or Zollinger Ellison Syndrome

Clinical Features of Gastrinoma

Diagnosis of Gastrinoma

Treatment of Gastrinoma

Glucagonoma or Hyperglycemic Cutaneous Syndrome

Diagnosis of Glucagonoma

Treatment- of Glucogonoma

Vipoma (Vasoactive Intestinal Peptide Tumor)

Diagnosis of Vipoma

Treatment of Vipoma

Cystic Neoplasm of Pancreas

Serous Cyst Neoplasm or Adenoma (SCN):

Mucinous Cyst Neoplasm or Adenoma

IPMN – Intraductal Papillary Mucinous Neoplasm

Treatment of IPMN

Pancreatic Cancer Risk Factors, Clinical Features, Diagnosis, Treatment, Neuroendocrine Tumors of Pancreas

The pancreas is an organ in the abdomen, situated behind the lower part of the stomach. The pancreas tissues are where pancreatic cancer first manifests itself. Along with producing digestive enzymes, the pancreas also produces hormones that aid in blood sugar regulation.

In addition to other growths, the pancreas may develop tumors that are cancerous or benign. The most common type of pancreatic cancer, pancreatic ductal adenocarcinoma, arises in the cells lining the ducts that drain the pancreas digesting enzymes.

In its initial stages, when it is most curable, pancreatic cancer is rarely discovered. This is because symptoms frequently don't manifest themselves until the disease has spread to other organs.

The Most common genetic mutation in the Carcinoma pancreas is K-RAS > p–16. 

Read this blog further to get a quick overview of this important topic Pancreatic Cancer: Risk Factors, Clinical Features, Diagnosis, Treatment, Neuroendocrine Tumors of Pancreas for SURGERY to ace your NEET PG exam preparation.


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Risk Factors of Pancreatic Cancer

Below are mentioned few of the risk factors for pancreatic cancer:

  • Smoking or tobacco
  • Hereditary Factors or genetic susceptibility [H3-AFP]
  • Hereditary pancreatitis 
  • HNPCC (hereditary non-polyposis colon cancer) 
  • Hereditary Breast and Ovarian Cancer (associated with BRCA - 2) 
  • Ataxia Telangiectasia 
  • Familial atypical multiple mole melanoma (FAMMM) syndrome 
  • Peutz-Jeghers Syndrome

Causes of Pancreatic Cancer

The exact cause of pancreatic cancer is unknown. Smoking and having specific inherited gene mutations are two factors that have been linked to an increased risk of this type of cancer.

Symptoms of Pancreatic Cancer

Pancreatic cancer signs and symptoms frequently don't appear until the disease has progressed. They may consist of:

  • back discomfort that originates in the abdomen
  • appetite loss or unintentional weight loss
  • Jaundice
  • Pale colored stools
  • Dark Urine 
  • Skin itching 
  • newly discovered diabetes or diabetes that is already present but becomes harder to control
  • Clots of blood
  • Fatigue
  • Most common symptom is Jaundice > weight loss. 
  • The most common symptom of Carcinoma head of the pancreas is Jaundice > weight loss.
  •  The most common symptom of Carcinoma Body and Tail Pancreas is Weight loss.
  •  Ampullary Carcinoma- Its most common symptom is Jaundice. Waxing and waning of jaundice with melena (seen every 2-3 months in 1/3rd cases)
Important Information

TROUSSEAU Syndrome - Migratory Superficial Thrombophlebitis seen in Malignancy (most commonly associated with carcinoma pancreas)

TROUSSEAU Sign - Carpopedal Spasm in Hypocalcemia

TROISIER’S Sign - Left Supraclavicular Lymphadenopathy (Virchow’s Node or signal node) 
Trousseau Syndrome

Diagnosis

  • Investigation of choice for Carcinoma pancreas is CECT

Radiological Signs 

  • Carcinoma head of the pancreas on Barium study
    • 1. Antral pad signs
Antral pad signs

2. Widening of C loop

3. Reverse 3 Sign of Frost Berg

Reverse 3 Sign of Frost Berg

4. Double Duct Sign

Double Duct Sign
  • Other signs in Carcinoma pancreas
    • Rose-thorn Appearance
    • Mucosal Irregularity
    • Scrambled Egg Appearance

Treatment of Pancreatic Cancer 

  • For Carcinoma Body and Tail Pancreas – Distal pancreatectomy is done.
  • For Benign tumor in the head of Pancreas – Enucleation is done
  • Carcinoma head of Pancreas
    • Whipple’s procedure - Pancreaticoduodenectomy (PD)
    • Longmire traverso procedure - Pylorus preserving Whipple’s procedure
  • For advanced or metastatic stage Gemcitabine is given
metastatic stage Gemcitabine
Whipple’s procedureLong wire traverso procedure (pylorus preserved)
1st anastomosis is Pancreaticojejunostomy
2nd anastomosis is Hepaticojejunostomy
3rd anastomosis is Gastrojejunostomy
1st anastomosis is Pancreaticojejunostomy
2nd anastomosis is Hepaticojejunostomy
3rd anastomosis is Duodenojejunostomy
Performed in anticlockwise fashion
Diagram, text

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Diagram

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Pancreaticojejunostomy

The most common site of anastomotic leak is Pancreaticojejunostomy (PJ) > Gastrojejunostomy (GJ) > Hepaticojejunostomy (HJ).

Most common complication of Pancreaticoduodenectomy is Delayed gastric emptying.

Most common cause of death after Pancreaticoduodenectomy is Cardio-pulmonary complications.

Most important predictor of survival is R0 resection. Types of resections

  • R0 resection – negative margin
  • R1 resection – microscopic positive margin
  • R2 resection – macroscopic positive margin

Most important margin in Pancreaticoduodenectomy is the Uncinate margin or Retroperitoneal margin or Superior mesenteric vessel margin. Survival in Carcinoma Pancreas

  • Stage I and II is 16-20 months
  • Stage III is 6-10 months
  • Stage IV is 3-6 months

Neuroendocrine Tumors (Net) of Pancreas

A category of malignancies known as pancreatic neuroendocrine tumors (pNET) can develop in the pancreas hormone-producing cells. Islet cell malignancies, commonly known as pancreatic neuroendocrine tumors, are extremely uncommon.

Small hormone-producing cells (islet cells), which are often present in your pancreas, are where pancreatic neuroendocrine tumors start.

Some pancreatic neuroendocrine tumor cells continue to secrete hormones, these tumors are referred to be functional tumors because they cause the body to produce an excessive amount of a particular hormone. Gastrinoma and glucagonoma are a couple of examples of these types of tumors.

These tumors are sometimes referred to as nonfunctional tumors since they rarely secrete an excessive amount of these hormones.

  • Most common Neuroendocrine tumor of Pancreases is Non-Functional pancreatic polypeptide cell tumor (PPOMA)
  • Most common functional Neuroendocrine tumor of the Pancreas is Insulinoma
  • Most common functional and Malignant Neuroendocrine tumors of the Pancreas is Gastrinoma
  • Neuroendocrine Tumors are symptomatic because of production of active substances. So, patients are
    • Symptomatic at an early stage
    • Diagnosed at an early stage
    • Treated at an early stage
    • Better prognosis - Neuroendocrine tumors > Adenocarcinoma

Diagnosis

  • Diagnosed is made in Laboratory by measuring active substance or its by-product
  • Investigation of choice for localization of Neuroendocrine tumors: SRS (Somatostatin receptor Scintigraphy) (as all Neuroendocrine tumors express Somatostatin receptors except Insulinoma)
  • Most common site of metastasis is Liver

Insulinoma

Insulinoma is one of several pancreatic neuroendocrine tumors (pNET) or islet cell tumors. These are uncommon cancers that originate in your pancreas' endocrine cells. They affect the endocrine cell that makes the hormone insulin, which controls the rise of your blood sugar (blood glucose) levels. More than 90% of insulinomas are benign tumors since they don't spread outside of your pancreas. Surgery is performed by medical specialists to treat and remove insulinomas.

It is the most common functional Neuroendocrine tumor of the Pancreas and is mostly Benign. The Most common site is equally distributed in the Head, Body, and Tail. In 5% of cases, it is associated with MEN-1. In MEN-1 insulinoma is malignant and has multiple lesions.

Clinical Features of Insulinoma

  • Characterized by Whipple’s Triad
    • Symptoms of Hypoglycemia
    • Blood glucose (45 – 50 mg/dl)
    • Improvement in symptoms after taking oral glucose
  • Neuroglycopenic symptoms
    • Dizziness
    • Headache
    • Confusion
    • Coma
  • Sympathetic overactivity leading to
    • Tachycardia
    • Palpitation
    • Excessive sweating
    • Tremors
  • It is a Painless condition associated with weight gain.

Diagnosis of Insulinoma

Gold Standard Investigation is 72 hours fasting. Insulin/ Glucose (ratio) more than 0.4 is diagnostic. The best pre-operative Test for localization is Intra Arterial Calcium injection with portal venous blood sampling. Overall best Investigation for localization is EUS (endoscopic ultrasound ) along with “Intra–Operative Palpation”.

Treatment of Insulinoma

  • For preoperative preparation, Diazoxide is given as it is directly toxic to beta-pancreatic cells so it decreases the insulin
  • For the Body and Tail Tumor - Distal Pancreatectomy is done
  • For head Tumor– Enucleation (since it’s benign) is done
TREATMENT OF INSULINOMA

Gastrinoma or Zollinger Ellison Syndrome

Gastrinomas are neuroendocrine tumors (NETs) that secrete gastrin and lead to the clinical illness known as Zollinger-Ellison syndrome (ZES). They are typically found in the duodenum or pancreas. Nearly equally frequently, a lot of gastrinomas form in the pancreas or the duodenum, and around 10% form as primary neoplasms in the lymph nodes of the pancreaticoduodenal region (gastrinoma triangle).

The majority of gastrinomas (75–80%) are sporadic, but 20–25% of them are connected to MEN-1, or multiple endocrine neoplasia type 1. More than 50% of gastrinomas are cancerous, and they can spread to the liver and local lymph nodes. Multiple endocrine neoplasia type 1, Zollinger-Ellison syndrome, and peptic ulcer disease are linked to one-fourth of gastrinomas.

It is the most common functional and Malignant Neuroendocrine tumor of the Pancreas. The most common site is Duodenum > Pancreas. 

In Duodenum Most common site is 1st part > 2nd part > 3rd part (4th part is not Involved). 75% sporadic and 25% associated with MEN 1. In all of the cases of Gastrinoma in MEN-1 common site is duodenum

90% of gastrinoma is present in the Triangle of Passaro’s or Gastrinoma triangle. Boundaries of Passaro’s Triangle are:

  • Junction of Cystic duct and CBD
  • Junction of Second and the third part of duodenum
  • Junction of neck and body of pancreas

It has increased Gastrin production leads to increase production of Acid causing Peptic Ulcer Disease:

gastrinoma triangle

Clinical Features of Gastrinoma

  • Most common symptom is Abdominal pain
  • Other symptoms include
    • Retrosternal heartburn
    • Dyspepsia
    • Diarrhea (acid induced): Nasogastric aspiration halts Acid induced Diarrhea
    • Has large ulcers or multiple ulcers or Jejunal ulcers or Refractory ulcers

Diagnosis of Gastrinoma

  • Gastrin more than 1000 Pg/ml is diagnostic
  • Basal Acid Output (BAO) more than 15 mEq/hour is also diagnostic
  • Best Provocative Test is Secretin Stimulation Test (release of gastrin more than 200 Pg/ml)
  • Investigation of choice for localization is Somatostatin receptor scintigraphy (SRS)

Glucagonoma or Hyperglycemic Cutaneous Syndrome

Pancreatic glucagonoma is an uncommon type of tumor. The pancreas releases glucagon, a hormone that collaborates with insulin to regulate blood sugar levels.

Large amounts of glucagon are produced by glucagonoma tumor cells, and these high levels cause severe and perhaps fatal symptoms.

Glucagonoma
  • It is Also known as “4” D Syndrome
    • Diabetes Mellitus
    • Dermatitis - Necrolytic Erythema Migrans (Most common symptom)
    • Deep vein thrombosis
    • Depression
  • Most common site of Tumor is Body and Tail of Pancreas

Diagnosis of Glucagonoma

  • Investigation of choice is increased Glucagon levels
  • Investigation of choice for localization is SRS (Somatostatin Receptor Scintigraphy)

Treatment- of Glucogonoma

As in glucagonoma the Tumor is located in body and tail, so we do Distal Pancreatectomy

Vipoma (Vasoactive Intestinal Peptide Tumor)

It is also known as Verner Morrison Syndrome or Pancreatic Cholera or WDHA Syndrome. There is an increase in VIP (Vasoactive Intestinal Peptides) which will lead to an increase in secretions causing watery diarrhea.

WDHA Syndrome includes:

  • Watery Diarrhea (4 – 6 Liters) leading to Loss of sodium, chloride, potassium, and bicarbonate Increased Random blood sugar, and calcium (Hyperglycemia and Hypercalcemia)
  • Hyperkalemia
  • Achlorhydria

The Most common site of occurrence is Tail and It is a medical emergency

Diagnosis of Vipoma

  • Diagnosis is based on VIP (Vasoactive Intestinal Peptides) levels
  • Investigation of choice for localization is SRS (Somatostatin Receptor Scintigraphy)

Treatment of Vipoma

  • Treatment of choice is Distal Pancreatectomy

Cystic Neoplasm of Pancreas

Most common Cystic lesion of Pancreas is Pseudocyst (75%).  The most common Cystic Neoplasm of the Pancreas is Mucinous Cystadenoma (MCN). 

Serous Cyst Neoplasm or Adenoma (SCN): 

Generally, it is Benign. The most common site of occurrence of serous cystic neoplasm is in the Head of the Pancreas. It is most commonly seen in females (5th-6th decade)

Pathological features of serous cystic neoplasm 

Individual cyst in SCN (Serous Cyst Neoplasm) is Microcystic and has a Sponge-like or honeycomb appearance

Clinical Features of serous cystic neoplasm 

Majority of the patients are asymptomatic. In symptomatic patients have Vague abdominal pain

Diagnosis of  Serous Cystic Neoplasm of Pancreas

  • Investigation of choice is CECT
  • On CECT
  • Central Stellate scar
  • Central Sunburst Calcification
Diagnosis of  Serous Cystic Neoplasm of Pancreas

Treatment of serous Cystic Neoplasm Of Pancreas

  • Observation
  • Resection is indicated if
    • Diagnostic uncertainty
    • Symptomatic
    • Size is more than 4 cm
      • On aspiration of Cyst content
  • Content is Serous
  • CEA is decreased
  • Amylase is decreased

Mucinous Cyst Neoplasm or Adenoma

Mucinous Cyst Neoplasm or Adenoma

It is the most common cystic Neoplasm of the pancreas. It is a premalignant condition. It is mostly common in females (5th-6th decade). The most common site is the Body and Tail of the Pancreas. It is Macrocytic. Most patients are symptomatic and have Vague abdominal pain.

Diagnosis of Mucinous Cyst Neoplasm

  • Investigation of choice is CECT (shows Peripheral Egg Shell Calcification)

Treatment of Mucinous Cyst Neoplasm

  • Surgical Resection of Tumor in all the cases
  • On aspiration of Cyst content
    • Content is mucin
    • CEA is increased
    • Amylase is decreased

IPMN – Intraductal Papillary Mucinous Neoplasm

It is a premalignant condition. It is common in both males and Females (6th and 7th decade). The most common site is the Head and Uncinate process. There is excessive secretion of mucin, and the whole pancreatic duct gets distended with the mucin causing obstruction.

It has 3 Types:

  • Main duct variety
  • Side branch variety
  • Mixed variety

Clinical features of IPMN

  • Recurrent attack of acute pancreatitis

Diagnosis of IPMN 

  • Investigation of choice is Endoscopy
  • On Endoscopy - Mucin extruding from Fish-Mouth Opening
Diagnosis of IPMN

Treatment of IPMN 

  • Partial pancreatectomy
  • On aspiration of Cyst content
    • Content is mucinous
    • CEA is increased
    • Amylase is increased
Treatment of IPMN 

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