Gastrointestinal Neuroendocrine Tumors Treatment By Dr Pradeep Jain

Gastrointestinal Neuroendocrine Tumors

Neuroendocrine Tumors (NETs) are neoplasms that arise from cells of the endocrine and nervous systems. Neuroendocrine cells make hormones that control digestive juices and the peristalsis used in moving food through the stomach and intestines. Digestive tract neuroendocrine tumors are slow growing rare tumors comprising less than 2 percent of gastrointestinal malignancies with location of the primary tumors in the lining of the gastrointestinal tract, most often in the stomach, appendix, small intestine, or rectum and pancreas.

Types of neuroendocrine tumour

NETs most often develop in the gut or pancreas. These tumours are sometimes grouped together and called gastroenteropancreatic neuroendocrine tumours (GEP NETs).

NETs of the gastrointestinal tract are most often arising from the lining of stomach, appendix, small bowel, and rectum. They are also called carcinoid tumours of gastrointestinal tract. Carcinoids most commonly affect the small bowel, particularly the ileum, and are the most common malignancy of the appendix.

NETs that develop in the pancreas are also called endocrine tumors of the pancreas.

These are all rare types of tumor and include –

  • Insulinoma – secrets insulin causes hypoglycemia with concurrent elevations of insulin, proinsulin and C peptide.
  • Gastrinoma- produces excessive gastrin causes Zollinger-Ellison Syndrome (ZES) with peptic ulcers and diarrhea.
  • Glucagonoma- produce glucagon which produces adverse effects on body like rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels.
  • VIPoma – produce vasoactive intestinal peptide which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome).
  • Somatostatinoma – produces the hormone somatostatin which causes hyperglysemia, achlorhydria, cholelithiasis, and diarrhea.


Neuroendocrine tumors are divided into –

1. Well differentiated neuroendocrine tumors- cells do not look very abnormal and are not multiplying rapidly. These tumors tend to be less aggressive.

2. Poorly differentiated neuroendocrine tumor- cells that look very abnormal and are multiplying more rapidly. Poorly differentiated tumors tend to be more aggressive.

3. Moderately differentiated tumors- differentiation of cells in between well differentiated and poorly differentiated..

Risk factor

Generally, the causes of NETs are unknown
Probable causes are-

Family history – multiple endocrine neoplasia type 1 (MEN1) syndrome, neurofibromatosis type 1 (NF1) syndrome, Von Hippel-Lindau syndrome (VHL)

For gastric NETs – atrophic gastritis, pernicious anemia, Zollinger-Ellison

Symptoms and signs

Majority of neuroendocrine tumors are asymptomatic, or they produce symptoms related to the mass effect of the tumors. The symptoms are usually nonspecific and mimic a variety of diseases. They may be discovered incidentally during routine computerized tomographic examinations (CT-scan) of the abdomen for unexplained symptoms, or during removal of the appendix. Neuroendocrine tumors of pancreas can be classified into functional or non-functional tumors. Functional neuroendocrine tumors are associated with symptoms related to the secretion of specific hormones by the tumor such as hypoglycemia in patients with insulinoma, or hyperglycemia in patients with glucagonoma.

Non-functional neuroendocrine tumors, on the other hand, are associated with symptoms related to the mass effect of the tumors such as intestinal obstruction and abdominal pain.

Symptoms of GI neuroendocrine tumors may include the following:
  Abdominal pain
  Change in stool color
  Weight loss and weakness for no known reason
  Feeling bloated
  Blood in the stool
  Pain in the rectum

Carcinoid syndrome –

this may occur if the tumor spreads to the liver or other parts of the body and the liver enzymes cannot destroy the extra hormones made by the tumor, high amounts of these hormones may remain in the body and cause carcinoid syndrome.
Symptoms of carcinoid syndrome include the following :

Redness or a feeling of warmth in the face and neck
Abdominal pain
Feeling bloated
Fast heartbeat


Patient’s medical history is evaluated in detail and a physical examination is done.
If a carcinoid tumor is suspected, blood and urine tests may be used to look for abnormal amounts of hormones and peptides produced by the tumor, including chromogranin A in blood and 5HIAA (a byproduct of serotonin) in the urine.

Newer markers –

N-terminally truncated variant of Hsp70 is present in NETs but absent in normal pancreatic islets.

High levels of CDX2, a homeobox gene product essential for intestinal development and differentiation, are seen in intestinal NETs.

Neuroendocrine secretory protein-55, a member of the chromogranin family, is seen in pancreatic endocrine tumors but not intestinal NETs.

Imaging tests

Ultrasound, CT-scans and MRIs may be performed to confirm the diagnosis, and to determine the exact location and size of the tumor, if it has spread to other organs, and whether it can be surgically removed

Triphasic CT Scanning –

provides images during three different phases of blood flow through the liver, offer a more accurate diagnosis than routine CT. These tests are often used to determine whether the tumor has spread to the liver or nearby lymph nodes. Barium X-rays- a barium X-ray is done to check for the presence of carcinoid tumors in digestive tract. Several types of barium studies are done depending on symptoms which include barium swallow/upper GI, barium enema and enteroclysis.

OctreoScan –

Neuronedocrine tumours express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modifications of somatostatin with a longer half-life., also called somatostatin receptor scintigraphy (SRS or SSRS), utilizes intravenously administered octreotide that is chemically bound to a radioactive substance, often indium-111, to detect larger lesions with tumor cells that are avid for octreotide.

Gallium-68 receptor PET-CT –

Somatostatin receptor imaging can now be performed with positron emission tomography (PET) which offers higher resolution, three-dimensional and more rapid imaging is much more accurate than an OctreoScan.

Fluorine-18 fluorodeoxyglucose (FDG) PET –

This scan is performed by injected radioactive sugar intravenously. Tumors that grow more quickly use more sugar. Using this scan, the aggressiveness of the tumor can be visualized

MIBG Scintiscan –

Some neuroendocrine tumors absorb the hormone norepinephrine. In this nuclear imaging technique involves giving patients an injection of MIBG, a protein similar to norepinephrine that is combined with a radioactive substance.

Radiation-sensitive imaging tests reveal how much MIBG has been absorbed, indicating the presence of a carcinoid tumor.

Upper endoscopy :

An endoscope is inserted through the mouth and passed through the esophagus into the stomach. Sometimes the endoscope also is passed from the stomach into the small intestine to see the abnormal tissue growth. In case of obvious growth, biopsy is taken to confirm the diagnosis.

Colonoscopy :

A colonoscope is inserted through the rectum into the colon to see abnormal growth. A biopsy from abnormal tissue is always taken to confirm the diagnosis.

Endoscopic ultrasound (EUS) :

A procedure in which an endoscope is inserted into the body, usually through the mouth or rectum. An ultrasonic probe is attached at the end of the endoscope.

Capsule endoscopy :

this is a noninvasive procedure to see all of the small intestine. The patient swallows a capsule that contains a tiny camera. As the capsule moves through the gastrointestinal tract, the camera takes pictures and sends them to a receiver worn on the outside of the body.

Biopsy :

Tissue samples may be taken during endoscopy and colonoscopy from abnormal tissues. The biopsied tissuesis viewed under a microscope to confirm the diagnosis.


Treatments may be aimed at curing the disease or at relieving symptoms (palliation).

Localized tumors

Surgery is the primary treatment for localized tumors and might be curative. Surgical removal of the tumor is usually the first treatment for gastrointestinal carcinoid tumors. Tumors that have not spread may be removed along with a small portion of healthy tissue surrounding the tumor. Depending on the location of the tumor and whether it has spread, additional surgery may be required to remove portions of the affected organ or nearby lymph nodes.

Surgery can be done by either open or minimal invasive method to remove neuroendocrine tumors and nearby lymph nodes. In minimal invasive method, a laparoscope is inserted into the abdomen through a small incision. Benefits of minimal invasive method includes reduce postoperative pain, short hospital stay, less wound complications and faster recovery. Metastatic and recurrent disease

In certain circumstances, complete removal of the tumor may not be possible. Role of surgery in metastatic disease is to reduce the tumor mass and can be performed before or concomitantly with medical treatment. Other means of cytoreductive procedures are available, such as radiofrequency ablation, laser therapy and embolization of liver metastases.

Chemotherapy –

Cytotoxic treatment has been the standard for advanced neuroendocrine pancreatic tumors. The standard combination chemotherapy regimens include the following:

1. 5-FU, dacarbazine and epirubicin in standard or intensified dosage
2. Lomustine and 5-FU combination
3. streptozoocin ± 5-FU ± doxorubicin combinations
4. cisplatinum and etoposide combination for poorly differentiated endocrine pancreatic tumors.

Biological treatment –

Somatostatin analogues and a interferons has proved effective in control of associated clinical syndromes related to hormone production and release (carcinoid syndrome, gastrinoma, glucagonoma, etc.) in up to 60% of patients. Tumor-targeted radioactive treatment is an option in the selected group of patients with tumors that present a high grade of uptake of [111In] pentaoctreotide (octreoscan) scintigraphy.
Biological treatments with a promising prospect include sunitinib, everolimus and bevacizumab when associated with capecitabine and oxaliplatin.

MIBG Radiolabeled Therapy

Some neuroendocrine tumors absorb a hormone called norepinephrine. These tumors may respond to a nuclear medicine technique called MIBG radiolabeled therapy. In this treatment, the patient is given an intravenous dose of MIBG, a protein that is similar to norepinephrine and is attached to a radioactive substance. The MIBG is absorbed by the tumor, permitting the radioactive substance to selectively destroy tumor cells.


Patients should be followed at 3-monthly intervals during treatment with cytotoxic agents or biological therapy in order to assess response to treatment. Patients undergoing curative surgery should be followed every 3-6 months for at least 5 years in order to detect eventual surgically removable recurrences. Examination should include specific or non-specific biochemical markers depending on the associated (or lack of) clinical syndrome. Imaging is based on CT or MRI every 6 months.


Details @


Preparing for Laparoscopic Surgery by Dr Pradeep Jain

Dr Pradeep Jain — Laparoscopic surgery is a form of minimal access surgery, which involves making a very small incision on the body of the patient and using a thin and lighted tube to pass through this incision, in order to perform the procedure. The most common problem where this procedure is used is for abdominal disorders like gall bladder stones and gynecological troubles in women such as fibroids and cysts in female reproductive organs. Laparoscopy surgery has become a feasible alternative to open surgeries as well as laparotomy surgeries, which involve larger incisions in the abdominal areas. The treason for popularity of laparoscopy is that it is less complicated and expensive as compared to conventional surgery as there is no hospitalization required in such cases and wherever required, the length of hospital stay is very short. Additionally, the surgery is less painful and complicated and the recovery time is much shorter than conventional techniques.

Laparoscopic Surgery

Preparation of Laparoscopic Surgery

Though laparoscopic surgery is a simple and easy procedure, still some preparation is needed for making it a success. Here are some tips to prepare yourselves for a laparoscopic surgery in india:

1. Being armed with proper knowledge and information about the procedure is the first step for being prepared for it. The patient has full right to ask all kinds of questions from his surgeon, as well as clarify his doubts before the surgery is performed. Proper understanding will remove his phobia and make him more comfortable about the surgery as well as confident about the doctor who is going to perform it.

2. They should also inform the surgeon about all the medical conditions he is undergoing such as diabetes and hypertension. The surgeon also needs to be informed about the medication he is taking regularly, such as aspirin, which may hamper the blood clotting process after the surgery. This will enable the doctor to tackle any complications which may surface during the surgery.

3. The patient must not eat or drink anything at least eight hours before the surgery, as in case of other types of surgeries. The operation is done under anesthesia and the patient must also discuss the possibility of drug allergies with the anesthesiologist.

4. Another thing which the patient needs to take care of on the day of the surgery is not to wear any valuable jewelry as it has to be taken off during the process. Also, he needs to take off stuff like dentures, contact lenses and glasses during the procedure.

5. Finally, the patient must take into consideration that fact that laparoscopic surgeries are mostly done on outpatient basis and he is most likely to be discharged on the same day. Since the patient might not feel strong enough after the surgery, he must arrange for a friend or family member to drive him home after the procedure is completed.

In a nutshell, laparoscopic surgery is a much simpler process for the patient as it offers very speedy recovery. But being well prepared can make things even easier for the patient.

Dr. Pradeep Jain has wide experience of GI, GI Once and Minimal Invasive Surgery.

Details @

Carcinoma Esophagus – Esophageal Cancer Treatment In Delhi


Carcinoma Esophagus

The esophagus is a muscular tube also known as food pipe in general public transmits food material from mouth (base of pharynx) to the stomach. Carcinoma of esophagus is one of the deadliest malignancies of human body. The incidence of this malignancy is increasing in general population due to life style modification as well as changes in environment.

Carcinoma of esophagus is divided into two types –

1. Squamous cell carcinoma – Cancer that forms in tissues lining the esophagus. Mostly found in upper and middle 1/3rd of esophagus. Incidence increases with age with most common age group between 55-60 years with male preponderance.

2. Adenocarcinoma – cancer that begins in esophageal lining cell that secret mucus. Most commonly found in lower esophagus and at the meeting point of esophagus and stomach. Commonly presented in patients with age group 50 years or younger.

Risk factors for Esophageal malignancy –

1. Smoking and alcohol – smoking for a long duration and chronic alcohol consumption

2. Esophageal inner mucosal lining damage from physical agents –

  • long term ingestion of hot liquids
  • caustic ingestion (corrosive poisoning)
  • radiation induced damage

3. Carcinogens in food and water – nitrates, nitrite, nitrosamine,
smoked opiates, fungal toxins in pickled
4. Obesity – increased risk for adenocarcinoma of esophagus. Incidence of gastroesophageal reflux increased in obesity due to lax lower esophageal junction to stomach which leads to Barrett’s esophagus. If condition is not reverted with time Barrett’s esophagus turns into malignancy.
5. Chronic iron deficiency anemia in females leading to plummer Vinson Syndrome
6. Congenital hyperkeratosis of palms and sole
7. Helicobactor pylori infection
8. Achalasia Cardia – long standing
9. Dietary deficiencies of molybdenum, Zinc, Vitamin A

Symptoms of esophageal malignancy

1. Dysphagia – Dysphagia is the most common presentation. Patient may have difficulty in swallowing of solid food in early stage of disease and solid as well as
liquid food in the late stage of disease. 2. Weight loss – recent onset and significant.
3. Coughing and choking during meal.
4. Change in voice – hoarseness.
5. Weakness and easy fatigability.
6. Pain behind sternum – occasional
7. Heart burn and reflux
8. Malena and sometimes haematemesis.

Diagnosis of esophageal malignancy

The patient is evaluated on the basis of history, symptoms and clinical signs. Along with routine blood test and X-ray some endoscopic and radiological investigations are done which include –

1. Barium sallow x- ray – thin barium is allowed to shallow and x-ray of esophagus taken. This shows the site and outline of tumor.

2. Endoscopy – the endoscope is passed through mouth to esophagus to see the inner lining of esophagus and tumor. If it shows any abnormal growth then a small piece of tissue from the growth is taken for confirmation of the diagnosis. These tissues are examined under a microscope for the presence of cancer.

3. Bronchoscopy – in cases of advanced tumor arising from upper ½ of esophageal an endoscope is passed into trachea (wind pipe) to rule out local spread of the tumor to lungs

4. Endoscopic Ultrasound – for early tumor endoscopic ultrasound is passed in esophagus to find out local spread of tumor.

5. For tumor staging radiological investigation like computed tomography (CT) scans of chest and abdomen and positron emission tomography (PET) scan are performed to determine outer spread of esophageal tumor to surrounding vital organs and distant spread to other organs.

6. Thoracoscopy and Laparoscopy – By this methods detection rate of lymphnodal and distal spread of esophageal malignancy is high.

Staging of esophageal tumors

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body.

According to AJCC Cancer Staging Manual, Seventh Edition (2010) cancer growth and spread can be staged by TNM system

Tumor (T) – means how deep the tumor has grown into the wall of the esophagus

Node (N) – tumor spread to lymph nodes

Metastasis (M) – metastasis (distal spread) to other part of the body

Based on combined results of T, N and M staging of cancer determined.

Tumor (T) is classified into
TX: tumor cannot be evaluated
T0: cancer is not detected in the esophagus
Tis: this is also called carcinoma in situ that means very early cancer
T1: tumor spread to the lamina propria and submucosal layers of esophagus
T2: tumor spread to muscular is propria
T3: tumor spread to the adventitia, the outer layer of the esophagus
T4: tumor has spread to surrounding structures of the esophagus, including the aorta, pericardium, large blood vessel, trachea, diaphragm, and pleural lining of the lung

Node (N) : N stands for Lymph nodes. Lymph nodes close to esophagus is called regional lymph nodes and those located in other part of body are distant lymph nodes.
NX: lymph nodes cannot be evaluated
N0: cancer cells not detected in lymph nodes
N1: cancer cells has spread to 1-2 lymph nodes in the chest, near the tumor
N2: cancer cells has spread to 3-6 lymph nodes in the chest, near the tumor
N3: cancer cells has spread to 7 or more lymph nodes in the chest, near the tumor

Distant metastasis (M):

this indicates whether the cancer cells has spread to other parts of the body
MX: Metastasis cannot be evaluated
M0: cancer cells has not spread to other parts of the body
M1: cancer cells has spread to another part of the body

Grading of esophageal tumor

G1: well differentiated
G2: mildly differentiated
G3: poorly differentiated
G4: not differentiated

Esophageal Cancer stageing

There are separate staging systems for both squamous cell carcinoma and adenocarcinoma of esophagus.

Staging of squamous cell carcinoma of the esophagus

Stage 0: Tis, N0, M0

Stage IA: T1, N0, M0

Stage IB:
T1, N0, M0
T2 or T3, N0, M0

Stage IIA:
T2 or T3, N0, M0
T2 or T3, N0, M0

Stage IIB:
T2 or T3, N0, M0
T1 or T2, N1, M0

Stage IIIA:
T1 or T2, N2, M0
T3, N1, M0
T4a, N0, M0

Stage IIIB:
T3, N2, M0

Stage IIIC:
T4a, N1 or N2, M0
T4b, any N, M0
any T, N3, M0

Stage IV : any T, any N, M1

Staging of adenocarcinoma of the esophagus

Stage 0: Tis, N0, M0

Stage IA: T1, N0, M0

Stage IB:
T1, N0, M0
T2, N0, M0

Stage IIA:
T2, N0, M0

Stage IIB: 
T3, N0, M0
T1 or T2, N1, M0

Stage IIIA:
T1 or T2, N2, M0
T3, N1, M0
T4a, N0, M0

Stage IIIB: 
T3, N2, M0

Stage IIIC: 
T4a, N1 or N2, M0
T4b, any N, M0
any T, N3, M0

Stage IV : any T, any N, M1

Treatment of Esophageal cancer

Patients with esophageal cancer are managed based on its staging. Overall general condition of the patients affects management.

Stage I –

Tis and T1aN0 stage – 
Endoscopic therapy like mucosal resection or submucosal dissection with the help of endoscopic ultrasound (EUS),

Photodynamic therapy,
Radiofrequency ablation
T1b N0 & T2 N0 stage – Surgery (esophagectomy) to remove the part of esophagus that contains the cancer

Stages II-III –

Chemoradiation followed by surgery (trimodal therapy)
Patient with squamous cell carcinoma with well preserved general condition chemotherapy and radiotherapy started before definitive surgery.
Patients with adenocarcinoma of lower end esophagus where stomach meet (gastroesophageal junction) are only chemotherapy is given before surgery. For smaller tumor (< 2 cm) only surgery is advised.
Patients with serious co-morbidities who are not candidate for surgery are managed with chemoradiation.

Stage IV –

Chemotherapy/ Radiotherapy or symptomatic and supportive care Treatment is given only for palliation to relieve the symptoms like pain, difficulties in swallowing etc.

Esophageal stenting (plastic/metallic) is done in situations where the patient is totally dysphagic and having esophagobroncheal fistula.
Patient who are unable to tolerate oral feeds a nasogastric tube may be required to continue feeding.
Some times gastrostomy/jejunostomy tube is required where patients become intolerant to nasogastric tube or tend to aspirate food.
Laser therapy is done in cases in which esophagus is totally occluded by cancer and the cancer cannot be removed by surgery. The relief of a blockage by laser can help to reduce dysphagia and pain


Chemotherapy may be given after surgery (adjuvant) to reduce risk of recurrence or before surgery (neoadjuvant) to down stage the disease.
Chemotherapy is cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks.
Recently epirubicin regimens is used in advanced nonresectable cancer.
Patients with adenocarcinoma with HER2 positive treated with targeted targeted therapy like trastuzumab.

Radiotherapy :

Radiotherapy is given before, during or after chemotherapy or surgery. It is also used in palliation to control pain.

Surgery is contraindications in following situation :

1. Locally advanced cancer engulfing adjacent vital structures like trachea, lung, pericardium, aorta recurrent laryngeal nerve
2. Esophageal Cancer with wide dissemination ( metastasis) to distant lymph nodes and vital organs
3. Severe co-morbidity involving cardiovascular and respiratory system

Surgical options :

Surgery is performed by either open or minimal invasive method depending upon patient’s general condition and availability of experts. Now a days minimal invasive approach of esophagectomy has become very popular among surgeons because of low surgical morbidity, short hospital stay and similar onchological outcomes.

Types of esophagectomy-

1. Transhiatal esophagectomy (THE)
2. Transthoracic esophagectomy (TTE) – thoraco abdominal Mc Keown’s & Ivor Lewis esophagectomy 

In thoracoabdominal approach – both the abdominal and thoracic cavities opened together.

Ivor Lewis esophagectomy – two-stage approach involves an initial laparotomy and construction of a gastric tube, followed by a right thoracotomy to excise the tumor and create an esophagogastric anastomosis

McKeown esophagectomy – three-stage approach which include incision in the neck to complete the cervical anastomosis.

Details @