von-Hippel Lindau Warrior in India

 

Have you ever said, "I'm fine, very good when you weren't because most people don't understand?"

I was diagnosed with a rare disease von Hippel-Lindau or VHL. VHL may occur in up to 10 organs of the body also there is a possibility of neuroendocrine cancer.VHL is a genetic form of cancer. VHL patients battle a series of tumors throughout their lives. Tumors can develop in the brain, spine, retina, kidney, pancreas, adrenal gland, inner ear, reproductive tract, liver, and lung. Lack of timely intervention can often lead to morbidity and mortality.

All people with VHL disease should be carefully followed by a physician or medical team familiar with the disorder.

The will to live is an unstoppable thing. Most people live only when they are about to die. 

There's a problem here.

Most Indians pooh-pooh vHL but when cells perceive a lack of oxygen (hypoxia), such as through a defect in the tumor suppressor gene (VHL), the transcription factor, HIF (Hypoxia-Inducible Factor), is not allowed to bind to the VHL protein. HIF is thus protected from degradation.

 The research professionals and members of the medical community around the world to better understand the VHL gene and its impact on cancer development. The outcome is Belzutifan (MK-6482; PT-2977)

As stated by Dr. Kaelin, “When you are studying about von Hippel-Lindau disease, you are not just studying about [the] …. disease … you are also now touching other diseases as well, where we can use the VHL gene to understand what is happening.” As such, the understanding of HIF involvement in tumorigenesis provides hope for the 40% of the world’s population who will be diagnosed with cancer at some point in their lives.

The unusual birth of the eye-catching child of fond parents after a miscarriage and foetus getting problems while in the womb, were lost in the thought that behind the outer shell there might lurk some sickness never known to humanity and the ill-fated, ill-starred child would have to endure the worst in all walks of life and face countless challenges my parents never thought of that.

.From my early childhood, Mum became a vital and integral part of my life, the magic charm of my gloomy and solitary life. She has always made me feel so special.

Faces beshrouded 'neath a mask; I can't shun curiosity, and I wear a grinning mask.Pretending to be what they truly are. You don't need to look too far.

Born with a soul of a mermaid who could only suffer pain since mermaids have no tears I suffered more acutely. My heart was like a sponge, sucking up feelings and emotions, even pain. Only Mum could understand my unsaid words.

I have spent a lot of time in recent years trying to forget unnecessary things so that I will have room in my brain attic for some things that may be more useful. For instance, I have forgotten the longest word in the English language-- “pneumonoultramicroscopicsilicovolcanoconiosi”, or was it, “floccinaucinihilipilification”¨?

and what these terms mean but I can never forget those wretched smiling faces on the balcony. My father called the ambulance at night due to my pain because of a hemorrhaging liver and took me to the hospital and it's that view, when I looked up to the balcony above that has clung to my memory forever like flies in flypaper.

Uncle,  aunt and the Didi singer at Kolkata who tried to swat her out of the way like a fly sitting on the wall can be easily swatted with a rolled-up magazine.

From childhood, I have not been as others were,I never enjoyed hop-skip-jump days that's for sure.Being a sick girl looking for the doctor's cure.Do you ever wonder just what God requires? Given just one life to face things where everyone conspires. Without any play-fellow at school thinking I am in need of some solicitude against the deluge of solitude.Parental solicitude was quite tireless.Father wasn't tough and prepared. With faith 80% heart's blockage gasping for air. His efforts nobody in the world could compare.Gave her daughter a new lease of life. Soon the commander, solver of every problem died, and the Warrior Princess was born, to face this life because life is not eternal neither do I have any option for mountains of books, chocolate bearing trees and rivers of coffee. I have to face this life head on.

My father perished soon after the transplant and my foxy uncle took our house from us and we were left penniless and homeless. It was then that my real tough times began and we had two choices ...death or preservation of life.

A lost  breadwinner, now who will bring a small bit of bread?Faithful bruvver of mine.Who had sworn, so I will be fine,affectionately said "There were many generous people who could do the duty, perform the responsibility he had sworn ardent, answering commitment to his father before his admission to FTII.

I can't care for you because I have a wife,I will look after you just a little later. After your death in the next life."

"I will do my duty after your death.When leaving sweet memories to ease away pain you step into the afterlife"

In the rhythm of ebb and tide of eternal time

I got my ineradicable place in the universe

Alone in endless, stillness, calmness of the universe

Life after death 

Spirit or soul 

Is there in every culture.

The great cycle of life and death

Seem as vague and hazy like a dream.

Darkness would wrap itself around me, 

filling me with a veritable ecstasy of emptiness

If when I die I will live again, 

And some thinking, feeling,

 Remembering part of me will continue.

Despite the ancient and worldwide

 Cultural traditions that cultural beliefs

They mystify and bring relief

Asserting an afterlife, immortality 

In ancient Mesopotamia, Egyptians, Hebrew, Greek, Romans, Old testament, The Gita, Chinese, Tantric, Anglo-Saxon

It feels like a formation of beliefs, wishful thinking,

If it was really true no matter what

And I can trust my gut

The door is slammed shut

I could satisfy my deep interests and ambitions

Only if I had proof the authenticity of the traditions

But if it's an endless dreamless sleep

A shadow so deep;

My passion would remain a forlorn hope

Fulfillment of my wishes has no scope

This perspective has given me

 A little extra motivation to stay alive!

Thrive and survive

In our vulnerability, 

Looking Death in the eye 

Don't make me breathe a sigh

Being grateful for every day 

The brief but magnificent opportunity

Life grants

Life is but a momentary glimpse of the wonder of this astonishing universe

Not a dream or spiritual fantasy

Karma says if you want happiness in life, never be an owner of love be a donor of love 

Woman who works in a slaughterhouse.Who is somebody's wedded Spouse,--Threatens to drop dead the very moment.I feel Life is one magical moment.Where dreams are woven.Keeping eyes open.Exploring each moment. Feeling the thrill of the moment

Why did I get Covid 19 despite voluntary isolation?

Taking  mask-wearing and social distancing lightly. Pass on infections to others harshly

 Tests are a preventive measure and only effective as long as you put in place other security measures

"Holy cow!" I could see the conspiracy,human tyranny, defendant spouse.

C-reactive protein and the D dimer rose defending the demoniac strength, We are no longer in same wavelength

Commenting on my daily titanic struggle.

I would define my life has been eaten up by the family trait lust…

There's a difference between frustration and determination

It's all in your mind Seek pluck till you find,I am gonna look for hope till my eyes go blind.

The immune system not having the capacity to distinguish between a new organ transplanted to save life destroys it instead which results in rejection.

The side effect in question? These medications may increase your risk of infection. 

 This almost implies that if you are taking some of these medications you will fall ill every time you pass by someone with the sniffles along with the big stuff, like the flu or tuberculosis. Or end up with Covid like me.

Neuroendocrine tumour is a part of vHL or other sporadic A 54-year-old actor gets neuroendocrine tumours and the nation gets stunned, staggers  and cries for him. Waves of worry in every person. He was an entertainer, actor.

A 41 year old woman who is struggling with several cancers and started after father perished with no idea how to get food the next day pulled herself up from the condition and is now back to starting point again.

Making an earnest appeal to the government I was once a child and have been suffering since 3 years old. Government acknowledged then rejected because children need to live. Oh! God amongst my all troubles why didn't you give me the aging ailment of Benjamin Button. I would have been back to 3  years old and with the support of the Government enjoying life with Mum.

Doctors opine, and one cannot help but agree, that in  some parts of the genetic cancer several victims of the syndrome avoid detection entirely, while others,battle throughout life.

Oftentimes the victims are reluctant to seek medical help, which is helpful as well as harmful.

“Chromosomes too are shuffled into oblivion, like hands of cards soon after they are dealt. But the cards themselves survive the shuffling. The cards are the genes. The genes are not destroyed by crossing-over, they merely change partners and march on. Of course they march on. That is their business. They are the replicators and we are their survival machines. When we have served our purpose we are cast aside. But genes are denizens of geological time: genes are forever.”

Genetic disorders exploits the fundamental logic of evolution unlike any other illness. If we, as a species, are the ultimate product of Darwinian selection, then so too is the disease which lurks inside me and I’m a freak of evolution. Evolutionary diseases can’t yet be undone, but some do have treatment to provide longevity.

To tackle the crisis there was a doubtful sanction or approval of support.

Then it entirely hypothetical, imaginary form to someone who then wrote a brief description of it. If this description of rare disease.

If we have luck enough to get the decision makers' children sick genetically being unable to assist them, let alone cure poor children she'll be desperate for a cure.

Even what remains discredited and truly eccentric will help save more lives than any pill or conventional medical guide. Or a conventional doctor, for that matter.

Could well mean that government funding for a cure will soon be at an end, support nonetheless for obscure and discredited diseases 

My story about my attempt to conquer tomorrow

 The unusual birth of the eye-catching child of fond parents after a miscarriage and fetus getting problems while in the womb, were lost in the thought that behind the outer shell there might lurk some sickness never known to humanity and the ill-fated, ill-starred child would have to endure the worst in all walks of life and face countless challenges my parents never thought of that.

From my early childhood, Mum became a vital and integral part of my life. She is the diamond of my life. I have a little mother, I call her Mum. She is the magic charm of my gloomy and solitary life. She had always made me feel so special.

Have you ever said, "I'm fine, very good when you weren't because most people don't understand?"

But my heart was like a sponge, sucking up feelings and emotions, even pain. Born with a soul of a mermaid who could only suffer pain since mermaids have no tears I suffered more acutely. I could hear the voice of the witch " Every step I took was as the witch had said it would be; I felt as if she were treading upon the points of needles or sharp knives." But this is fantasy, let's come to the scientific view behind the pain.

I became a Guinea pig at such a young age!

Through all hardships and forfeitures of every kind--supported by the one thought in every facet of life. When life is sheer willpower hanging by two or three threads, she tells of the wondrous things in my rare and strange life and we together have journeys and magnificent adventures mostly making rounds of hospitals.

This all happened, and we are put in such situations because of my sly and foxy uncle and his tricky strategies.

Yesterday standing in the balcony I hurled out curses steadily against the uncle,  aunt and the Didi singer who tried to swat her out of the way like a fly sitting on the wall can be easily swatted with a rolled-up magazine. 

They made a cunning plan to shove her out of the way so that without her the family doesn't insist upon that the inheritance belongs to the family because she was the Achilles heel and without me parents won't survive and they could easily take over the family estate. Father didn't have sufficient money for her liver transplant when they hatched the wretched plan but had the mind to fetch the moon for me.

Have patience until I unfold the story of my life at the right pace and precision so that you can judge yourself from each slice of life, I present to you.

He is the youngest son of my grandparents. But I must say here that my father was a naive man of which fact I presume his siblings had taken advantage.

Grandma was a brainless, mean-minded prejudiced woman who could easily be brainwashed. She had a big ego and an inflated sense of self and thought herself above everyone because her husband had money and means. She believed in racism.

She never praised anyone other than her daughter and youngest son. She was always partial towards her youngest son and thought him to be very clever. Clever he was but in a crafty way. It is because of those shrewd, wily, and cunning ways of his that I am going through all this poverty, hoping that in my life story like in all fiction the good will end happily and the bad unhappily.

It is said ‘Excess of everything is bad.’ Such is the case with excessive wealth. Excess of wealth makes one haughty and full of false pride. The desire for more wealth makes a man greedy. A man who has amassed abundant wealth is prone to sensual pleasures. He gets entangled in the enjoyment of more and more worldly pleasures and loses his inner vision. Ultimately, he loses his peace and happiness.

Lust, greed, anger and false pride, etc. can act very strongly on our mind and can lead it astray and thus cause great damage. These strong impulses of sense organs must be brought under full control. This can be done by cultivating a strong willpower through proper understanding, strong and steady determination, and self-confidence.

I could never infer the whole nature of the sly lustful uncle's strangely showing off his superiority from the parts I could see then but as I said life alerted us many times, but we never understood. My father was not clever enough with no twists in his mind. It was not his fault. He realized it all when he was in his early sixties, just a few days before his departure from this world.

The uncle was married after Grandpa's death to a woman puffed up with self-importance. She is a worthy better half of her conspiring husband, thinking her to be the undisputed queen of the elites of the society

Both were adept in the art or process of gaining the advantage in situations employing crafty or ingenious ploys "Wherever you find a great man, you will find a great mother or a great wife standing behind him"--- in this case, was the wife.

From childhood, I have not been as others were

I never enjoyed hop-skip-jump that's for sure,

Being sick girl lookin' for the doctor's cure

In my adolescence couldn't satisfy my

Desire to fly

Interests hobbies passions weird desires

Do you ever wonder just what God requires?

Given just one life to face things where everyone conspires

Put me in a life of big mess

Without any play-fellow thinking

Terribly lonely I am need some solicitude against the deluge of solitude

Paternal solicitude was quite indefatigable

Father wasn't tough and able

With faith heart' blockage

Gasping for air

With whole world's a-watchin'

Peeking out and stare

His efforts nobody in the world could compare

Gave her daughter a new lease of life

When the commander, solver of every problem died

And passed away

My father perished soon after the transplant and my foxy uncle took our house from us and we were left penniless and homeless. It was then that my real tough times began and we had two choices ...death or preservation of life.

Not only we faced shocking poverty where we didn’t have money for food the next day, but I acquired MDR- TB living in shabby houses and changed houses seven times hounded by landlords. 

My brain literally changed in chemical composition when I understood the frightfulness and the oddity of my nasty lingering illness and its larger economic implications.

 When in poverty, you face medical embarrassments, the humiliation of asking for financial help, physical suffering which is always there money concerns for food, medicines and rent.

Living in a lousy cramped house I faced many acts of kindness,  many acts of madness but didn't flop down to the bottom. Itching or scratching diseases have solid attention from the government and the public but in my case, many vociferous suggestions, whispering advice came to me disapproving my smiling visage.

 My brain tumours are the rarest ones from 1902-2013 only 132 cases have been reported globally. A fellow remarked after he saw the picture of the scan of my brain tumours.

" you have more tumours in the brain than people have lice in hair.''

In every act of betrayal, 

Every crime inflicted

 You can smell the money.

 ‘Money’ and ‘Power’ are the root causes in every act of felony, every crime, every treachery committed since time immemorial. 

Money, gold, holds allure because it gives power, a lavish lifestyle and many are ready to harm a life for its powerful charisma.

 Money tempts most people to wrongdoing. 

Crime is as old as humanity.

 Thus, it is since ancient times that brothers are slaughtering brothers for the power of the throne and the wealth it brings along. 

Slaughtering, poisoning, strangling, asphyxiating, backstabbing, but achieving money and power and destroying every life on the way. 

Such is the queer nature of the human race.

Breathing is a race, 

With longing and restlessness everywhere

Bearing grief every day 

All my life in a certain way 

To see if you feel alive

Or just existing muddled

When life was sheer willpower hanging by two or three threads

A lost  breadwinner, now who will bring a small bit of bread,

Faithful bruvver of mine.

Who had sworn, so I will be fine,

Affectionately said 

"There were many generous people who could do the duty, perform the responsibility 

he had sworn ardent, answering commitment to his pater.

I can't care for you because I have a wife 

I will look after you later

After your death in next life."

"I will do my duty after your death

When leaving sweet memories to ease away pain you step into the afterlife"

Karma says if you want happiness in life, never be an owner of love be a donor of love 

Woman who works in a slaughterhouse

Who is somebody's wedded Spouse,--

Threatens to drop dead the very moment

Whereon the stars in secret influence comment;

Life is one magical moment

Where dreams are woven

Keeping eyes open

Exploring each moment

Feeling the thrill of the moment

Why did I get Covid 19 despite voluntary isolation?

Ignorance prevails

“Ignoring isn't ignorance,

 Ignorance requires guts, boldness

Gloat knowledge wisdom

Prancing dancing scatty smartie

Experts have also strongly suggested

 Solely relying on testing as a safeguard 

You can not expect to be a lifeguard

 People making ‘lax’ and taking other safety measures

For thoughtless pleasures, taking delight in certain measures

Taking  mask-wearing and social distancing lightly

 Pass on infections to others harshly

 Tests are a preventive measure and only effective

 As long as you put in place other security measures

"Holy cow!"

I could see the conspiracy,

The human tyranny,

Defendant spouse 

As my  C-reactive protein and the D dimer rose

 Defending the demoniac strength

 We are no longer in same wavelength

Commenting my daily titanic struggle

Being a  Mere pawn on the chessboard of life

Ordained my death 

With an easy breath

Blindness and ignorance, Will lead you nowhere,

Unless you are aware

Long lament of the discreet 

The parallel lines shall never meet.

I would define my life as the family trait lust…

And all but forever lost.

The rabbit runs faster than the fox, 

Because the rabbit is running for his life 

While the fox is only running for his dinner.

There's a difference between frustration and determination

It's all in your mind

Seek pluck till you find

I am gonna look for hope till my eyes go blind

I had a liver transplant owing to several tumours in the liver which could not be taken out individually causing excruciating pain due to frequent haemorrhages in 2008. The largest lesion caused splaying of the portal vein around the lesion. Hepatic veins were compressed and displaced by the segment 4&8 mass lesion. I had two episodes of bleeding in the hemangioblastomas and required hospitalisation.

The transplanted liver needs the immune system to be suppressed so that it isn’t rejected like any pathogen. Immunosuppressants are expensive life-saving medicines. I am on immunosuppressive medicines for life.

The essence behind continuing an immunosuppressive regimen is that the transplanted organ into the body of the host is not similar in genetic structure(DNA) of the recipient.

We have been endowed with a wonderfully complex structure called the immune system to protect us from viruses which are essentially nucleic acid DNA or RNA.

Hence, the immune system not having the capacity to distinguish between a new organ transplanted to save life destroys it instead which results in rejection.

The side effect in question? These medications may increase your risk of infection. 

In general, however, the medication causes all or part of your immune system to “turn off” so that your body doesn’t go into attack mode, waging war against whatever it sees as a foreign invader. 

.

 This almost implies that if you are taking some of these medications you will fall ill every time you pass by someone with the sniffles along with the big stuff, like the flu or tuberculosis. Or end up with Covid like me.

I was diagnosed with a rare disease von Hippel-Lindau or VHL. It is a genetic form of cancer. VHL patients battle a series of tumours throughout their life. VHL may occur in up to 10 organs of the body also there is a possibility of neuroendocrine tumours.

It is also understood  mutations of VHL genes are also part of causes of other tumours including breast, colon etc.

VHL is the key to understanding how tumors grow and how potential theories can inhibit angiogenesis.

VHL is a tumor suppressor protein that is localized in the nucleus or cytoplasm, the extent to which being dependent on cell density.

The hypoxia-inducible transcription factors have also been shown to play a crucial role in tumour promotion in other cancers including breast, brain, colon, gastric, lung, skin, ovarian, prostate, renal, pancreatic. Increased levels of growth factors result in angiogenesis.

Together, these esteemed researchers provided an understanding of how cells can sense and adapt to changing oxygen levels and how this results in cancer, such as in brain, bladder, breast, colon, ovarian, kidney, and pancreatic cancers.

When cells perceive a lack of oxygen (hypoxia), such as through a defect in the tumor suppressor gene (VHL), the transcription factor, HIF (Hypoxia-Inducible Factor), is not allowed to bind to the VHL protein. HIF is thus protected from degradation.

VHL is a genetic form of cancer. VHL patients battle a series of tumors in up to 10 parts of the body throughout their lives. Tumors can develop in the brain, spine, retina, kidney, pancreas, adrenal gland, inner ear, reproductive tract, liver, and lung. Lack of timely intervention can often lead to morbidity and mortality.

As stated by Dr. Kaelin, “When you are studying about von Hippel-Lindau disease, you are not just studying about [the] …. disease … you are also now touching other diseases as well, where we can use the VHL gene to understand what is happening.” As such, the understanding of HIF involvement in tumorigenesis provides hope for the 40% of the world’s population who will be diagnosed with cancer at some point in their lives.

The VHL gene and its impact on cancer development. 

Thanks to this research, the FDA has approved eight drugs for the treatment of kidney and breast cancers. These agents target the regulation of cellular growth factors (the downstream consequence of elevated HIF levels).

When I told my doctors about it, " send me your writing please"

After completing their medical degrees do they plunge into the world of unique diseases, keep themselves updated, keep track of all those maladies?

Life is so meaningful, so wonderful, a little burst of kindness, softness can bring a colossal burst of Sunshine which can't be done too soon because you don't know how soon it will be too late. I was diagnosed with genetic cancer and currently, I am getting chemo for metastatic neuroendocrine tumors. I am a zebra, Warrior Princess Anchor my anchorless ship floating around the deep sea. I survived my liver transplant on this day 13 yrs ago. I have faith in me I can win the war of life 

When life was sliding out of me 

Hope roused the warrior inside me

 And I started my journey

Neuroendocrine tumours (NET)

 Neuroendocrine tumours (NET) are a group of diverse neoplasms arising from cells of neuroendocrine origin. 

What are neuroendocrine tumours (NETs)?

Neuroendocrine tumours (NETs) are rare tumours that start in neuroendocrine cells. You might also hear these tumours called neuroendocrine neoplasms (NENs) or neuroendocrine carcinomas (NECs). 

There are a number of different types of NETs. The type you have depends on the type of cell that the cancer started in. 

Most NETs develop slowly over some years. They may not cause symptoms in the early stages. It’s not unusual for people to find that a NET has already spread to another part of the body when they are diagnosed. 

Neuroendocrine cells have traits similar to those of nerve cells and hormone-producing cells. Neuroendocrine tumors are rare and can occur anywhere in the body. Most neuroendocrine tumors occur in the lungs, appendix, small intestine, rectum and pancreas.

The neuroendocrine system

The neuroendocrine system is made up of nerves and gland cells. It makes hormones and releases them into the bloodstream.

Neuro means nerve and endocrine refers to the cells of the endocrine system. The endocrine system is a network of glands and organs in the body that make hormones. It is also called the hormone system.

There are neuroendocrine cells in most organs of the body, including the:

• food pipe (oesophagus)
• stomach
• lungs
• small and large bowel
• pancreas
• liver

Neuroendocrine tumors are cancers that begin in specialized cells called neuroendocrine cells. Neuroendocrine cells have traits similar to those of nerve cells and hormone-producing cells.

Neuroendocrine tumors are rare and can occur anywhere in the body. Most neuroendocrine tumors occur in the lungs, appendix, small intestine, rectum and pancreas.

What neuroendocrine cells do

Neuroendocrine cells have different functions depending on where they are in the body. They control how our bodies work. This includes our growth and development, how we respond to changes such as stress, and many other things. 

For example, neuroendocrine cells of the lung make hormones that control the flow of air and blood in the lungs. And neuroendocrine cells of the gut (digestive system) make hormones to control:

• the production of digestive juices
• the muscles that move food through the bowel

Where NETs start

NETs can start in different parts of the body. Like all cancers, NETs are named after the place they start growing. For example, a NET that starts in the lung is called a lung NET. This is the primary cancer. If the cancer spreads to another part of the body, it’s called secondary cancer. 

Around 5 out of every 10 NETs (50%) start in the digestive system. This is also called the gastrointestinal (GI) system. It includes the:

• stomach
• small and large bowel
• pancreas
• back passage (rectum)

Around 2 out of every 10 NETs (20%) start in the lung. NETs can also start in other places such as the:

• food pipe (oesophagus)
• appendix
• skin
• prostate
• womb
• adrenal, parathyroid and pituitary glands

Neuroendocrine neoplasms (NENs) are rare malignancies of the aerodigestive, genitourinary and integumentary systems. Their histologies vary from well-to-moderately differentiated neuroendocrine tumors (NETs) to poorly differentiated neuroendocrine carcinomas (NECs) and their natural history has been described in several publications . Most studies are limited due to the small number of cases, inconsistent follow-up or retrospective nature but it is clear, however, that the incidence of NENs is increasing  and that, at least for certain subtypes, survival might be improving.

NENs show a spectrum of behaviors and this makes their treatment challenging. Some exhibit an indolent, slow growth pattern, while others parallel the more aggressive, rapidly spreading tumors such as small cell lung cancer (SCLC); in between there are neoplasms of intermediate malignant potential. Research so far has identified stage, site of origin and differentiation,  as well as proliferative indices (Ki-67, mitotic count) as important prognostic factors and multiple scores have been published, trying to predict survival in metastatic disease or recurrence after curative surgery. In general, well- differentiated tumors progress slowly and surveillance may be the best approach in some cases, whereas poorly differentiated neoplasms require urgent aggressive chemotherapy and are associated with markedly shorter survival.  Tumors of small bowel origin tend to have a better prognosis  compared to NENs originating in the pancreas. The effect of other factors such as age, race , resectability , performance status  or even marital status  has similarly been examined in several publications. Most medical decisions nowadays consider tumor of origin, staging, but also tumor differentiation and mitotic indices (values that have formed the basis of the current grading system ).

Recently, significant progress has been observed not only in our understanding of the biology and genetics of NET but also in the diagnosis and treatment.

Besides, newer classification and staging system have been adapted and guidelines published to help to establish a more standardised approach.

 Although some series report slightly higher incidence in men compared to women, there appears no significant difference in terms of gender. The prevalence of the dis-

ease is however estimated to be much higher and ranks only second after colorectal cancers among gastrointestinal (GI) tumours . Although NETs may occur at any age, it is more common after the age of 50 . NETs may be associated with familial genetic neuroendocrine tumour syndromes such as multiple endocrine neoplasia (MEN) syndromes (MEN-1 and MEN-2), neurofibromatosis type 1, von Hippel-Lindau (VHL) disease, tuberous sclerosis and Carney complex. 

In patients with these syndromes, the age of diagnosis is 15–20 years lower than those with sporadic NETs.

 NETs are usually slow-growing tumours. They can arise from many organs but commonly from GI tract and pancreas, lung, thymus and other endocrine organs. 

NETs may synthesise and secrete peptides and/or amines. These secreted peptides/amines can be used as tumour markers, and they may lead to clinical symptoms.

NETs have some common histopathologic characteristics. They show similar  immune reactivity to pan-neuroendocrine markers, chromogranin A and synaptophysin.  Neuron-specific enolase (NSE), CD56 and CD57 are less specific markers; they can be used to identify poorly differentiated NETs. Immunohistochemical  assessment of specific hormone expression is not routine in pathological evaluation,  and positive immune reaction for hormone expression in the tumour tissue does not  indicate that the tumour is functional.  NETs usually express somatostatin receptors; therefore, somatostatin expression  can be used both diagnostically and therapeutically. Somatostatin receptor imaging ( 111 In-DTPA-octreotide or preferably  68 Ga-DOTATATE) can be used for initial  staging, follow-up and selecting patients for peptide receptor radionuclide therapy  The role of newer PET tracers warrants further validation for routine clinical practice. Endoscopic evaluation of the patients with esophagogastroduodenoscopy, colonoscopy, double- balloon enteroscopy or capsule endoscopy  is critical according to the localization of the primary tumour and also in patients with  primary unknown metastatic  neuroendocrine tumour or carcinoma.

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors secreting   various bioamines and peptides arising from neuroendocrine cells in the endocrine  and central nervous systems. NETs are responsible from approximately 0.5 % of all cancers.

The incidence and prevalence of NETs have increased about fourfold for the last 30  years because of improvement in the diagnostic techniques. PNETs are more  aggressive tumors compared with NETs originating in the other sites. Also, most of  PNETs are malignant and tend to be in advanced stage at the time of diagnosis.  Gastrointestinal tract is the most common location and is responsible for two-thirds  of NETs. Small bowel is the most common primary site of GEP-NETs in the   developed countries. PNETs are divided into nonfunctional and functional tumors  which secrete hormones and peptides. In association with hormone and peptide  secretion, functional endocrine tumors may be symptomatic. Bronchopulmonary  system is the second most common location of NETs. These tumors consist of   one-third of all NETs. Typical and atypical carcinoids of the lung tend to slowly  grow. Most of nonfunctional lung carcinoids have been incidentally diagnosed.   The prognosis of NETs associates with their location, functional status, differentiation, and initial stages. In advanced stage, the prognosis is poor. However, the  overall survival of well-differentiated and localized NETs is longer. The best   survival rates are observed in patients with NETs arising in the rectum and appendix. The 5-year survival rates of these tumors are excellent with over 90 %.

Cancerous or non cancerous

There is some debate among doctors about how NETs should be grouped and what they should be called. NETs develop in different parts of the body and behave in different ways. For example, some NETs grow slowly while others are faster growing. 

All NETs are malignant (a cancer) by definition. Some NETs are diagnosed early and you might be able to have treatment to cure it. 

More recently doctors have been calling them neuroendocrine neoplasms (NENs). This is an umbrella term for this group of disorders. Then depending on how slow or fast growing the cells are they are called either neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs).

NETs are usually slower growing and the cell changes are called well-differentiated. NECs tend to be faster growing and the cell changes are called poorly-differentiated.

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