Critical Review of Samutthanavishesha of Arbuda W.S.R to Hepatocelluar Carcinoma

Introduction

Cancer is one among the most serious and potentially challenging, life threatening diseases of the present era. Science is not a sudden invention. It is a gradual evolution. Ayurveda as science is no exception to it. An urge to soothe the sufferings is as old as the urge for a secure life. The oriental thinking found the path to mitigate the sufferings – be it physical, mental or spiritual, in the form of science of life, i.e. Ayurveda. The imperishable fundamentals of Ayurveda which were laid down by the great sages of olden days are still applicable because of their scientific & spiritual eternal background. Such fundamentals must be subjected to scientific research not only to prove its certainty, but also to add something to the existing knowledge.

The World Health Organization has stated that cancer is the most deadly challenge to be met in the 21st century. Hepatocellular carcinoma is the most common type of liver cancer and constitutes 90% of cancers of liver globally. Approximately, 7.5 lakhs of new cases of HCC per year occur globally, which makes HCC the 5th common cause of cancers affecting humans. It is more common in men than in women. 

Arbuda, Granthi, Gulma are the diseases described in Ayurvedic classical texts with abnormal growth as dominant presentation. Clinical presentation, diagnosis, prognosis and management of abnormal growth depends on the site and severity of manifestations. The Samuthanavishesha (etiological diagnosis), Adhistana-vishesha (pathological) and Vikaravishesha (cinical diagnosis) of Arbuda, Granthi, Gulma explained in ancient literature have an important role in the understanding of Neoplastic disorders described in biomedicine.

Sushruta described saptavida vyadhi according to the origin or the cause of the disease.Proper understanding of Samutthanavishesha,i.e understanding of etiological factors will help in early diagnosis, which plays an important role in preventive, curative aspects of Hepatocellular Carcinoma and better intervention apart from deciding the prognosis.

So, here an attempt was made to understand “Critical review of Samutthanavishesha of Arbuda w.s.r to Hepatocellular Carcinoma”under the umbrella of saptavidha vyadhi, in search of probable etiological factors of Hepatocellular Carcinoma as per Ayurveda.

Methodology

This conceptual study was conducted by observing and analysing the information available in classical textbooks, research articles, journals and web. The collected details were critically studied, analyzed, discussed and conclusions were drawn.

Discussion

Samutthanavishesha

The word Samuthana refers to Hetu/Nidana (etiological factor) and Vishesha refers to specific. Hence, the term samutthanavishesha implies specific nidana of the vyadhi.

In this present era of modernization, people are neglecting the causative factors of the diseases and rushing towards treatment methodologies. It is the need of the hour to concentrate on the concept of “Nidana parivarjana chikitsa”i.e. towards causative factors. 

Yakrit Arbuda Nidana in General 

In classics, we do not find specific terminology such as Yakrit arbuda. Yakrit (Liver) is one among Kostanga mentioned in our classics. Yakrit (Liver) and Pleeha (Spleen)are the moola (root) of Raktavaha srotas. Hence, vriddhi (increase in size) of Yakrit is considered under the umbrella of Pleeha vriddi.

This Yakrit vriddhi occurs in two forms¹

1. Chyuta vriddi (by displacement)

2. Achyuta vriddi (by increase of blood)

Chyuta vriddi occurs by Sthanat chyuti because of nidanas (causative factors) like Atisankshobath (travelling in excess), Atiyanath (riding a vehicle), Atichesta (strenuous exercise), Ativyavaya (over indulgence in sex), Atiadhwa (walking a long distance) and Achyuta vriddi occurs by Vyadhikarshana (suffering from chronic disease).²

Arbuda in Yakrit cannot be considered as Chyuta variety. Basically, we understand Arbuda as a Mamsa pradoshaja vyadhi.³

According to Acharya Charaka, in achyuta vriddhi, Shonita and Rasavriddhi leads to Yakrit vriddi. Further, Chakrapani comments that Mamsa Pradoshaja vikara also leads to Raktavriddi, Raktavahamoola vriddi and Raktavaha srotodusti. Hence, Vyadhikarsana (suffering from chronic disease) is the main nidana for acyuta vriddhi of Yakrit, and hence for Yakrit arbuda.⁴

Understanding of Yakrit Arbudanidana / Samutthanavishesha Under the Umbrella of Saptavidha Vyadhi 

Saptavidha dukkha (seven types of disease of different origin),which can be considered for proper understanding of etiological factors of newly emerging disease.These are classified on the basis of multiple factors, varied from genetic susceptibility, extrinsic and idiopathic causes of the disease

I. Adhyatmika Factors as Nidana

Diseases caused by Vata, Pitta, Kapha along with Raja and Tama causes Adhyatmika vikaras. Disease pertaining to oneself is called Adhyatmika vyadhi (disease of one’s own body).⁵

Acharyas mentioned 3 types of Adhyatmika vyadhiis⁵

a) Adibala pravritta as nidana for Arbuda

b) Janmabala privritta as nidana for Arbuda

c) Doshabala privritta as nidana for Arbuda

a) Adibala pravritta as nidana for Arbuda:⁶ Acharyas mentioned dusta Shukra (sperm) and Shonita (ovum) as one of the causes for certain diseases like Kusta (skin disorder), Arsha (hemorrhoids) etc to occur. Here, dusta (vitiated) Shukra & Shonita implies dushti (vitiation) of Vata, Pitta, Kaphadoshas present in Shukra and Shonita. If it gets vitiated, then it produces vyadhi (disease).This can be correlated to Hereditary disorders.

Heredity refers to the genetic transmission of traits from parents to offspring. Some genetic conditions are caused by mutation in a single gene.

Acharya has quoted a few examples of diseases like Prameha, Kushta, Arsha, Kshaya and he mentioned adayaha (etc), which includes all the diseases that holds good for the disease Arbuda also.⁵ Hence, Adibala (heredity) can be considered as a possible nidana for Yakrit arbuda.

Hepatocellular carcinoma is a complication of Haemo chromatosis⁷ induced cirrhosis. Primary mechanism of haemochromatosis appears to be the genetic, in which the defect may either lie at intestinal mucosal level causing excessive iron absorption or at post absorption excretion level leading to excessive accumulation of iron.⁷ Thus genetic abnormality that is Adibala privritta acts as nidana for Yakrit arbuda and Hepatocellular carcinoma.

b) Janmabala Privritta as nidana for Arbuda:⁸ 

When a pregnant woman consumes ahita ahara (improper dietetics) and does ahita vihaara (improper regimes), it causes apachara (injury) to garba (foetus) and act as Janmabala (congenital) nidana (factors) leading to certain disorders in the growing foetus. This can be correlated to congenital disorders.

Congenital disorders are conditions existing at birth and often before birth or develops during foetal life

If garbini (pregnant lady) consumes Santarpana nidana (over nourishing), nidanas (causative factors) described under Gulma, Udara, Kamala in which Arbuda may be probable avastabedha (form of disease occurrence), then the baby may be susceptible to conditions like malignancy.^9,10

In current medical practice, over nutrition like excessive vitamin and mineral intake may lead to deposition in foetal liver, leading to disturbance in Alpha - feto protein which may act as a predisposing factor for Hepatocellular carcinoma.

Wilson’s Disease and Alpha-1 Antitrypsin - can be considered as congenital cause for Hepatocellular carcinoma.⁷ Hence, it specifies regarding ^Janmabala (congenital factor) as one among the ^nidana for the occurrence of Arbuda.

c) Doshabala as nidana for Arbuda:¹¹Amount of vitiation of Vatadi dosha because of consumption of mithyahara (faulty dietetics) and mithyavihara (faulty regiems), acts as nidana for occurrence of diseases like Arbuda.These can be classified as -

1. Raktadusti nidana

Atiushna ashana: If taken in excess quantity for longer duration, it aggravates Pitta and it causes the Dhaatu paka (inflammation) in the yakrit and leads to the diseases such as Kamala;further indulgence in nidana may lead to Yakrit arbuda. ¹² 

Aflatoxin exposure is a major risk factor for developing HCC.It is a fungal toxin produced by Aspergillus flavus and Aspergillus parasiticus. Storage of crops in hot humid conditions can promote the growth and accumulation of Aflatoxin - producing fungi.  

Atilavana ashana:Aatilavana rasasevana (intake) has adverse effect on the shareera (body) by vitiating the Sweda, Ambuvaha and Pranavaha srotas, leading to the shotha(inflammation).¹³ Too much sodium consumption leads to a series of changes in the liver - such as mishapen cells, higher rates of cell death and lower rates of cell division - all of which can lead to liver fibrosis.¹⁴

Atikshara ashana: Ksharaaggravates Pitta and it causes the Dhaatu paka (inflammation) in the yakrit (liver), leading to the diseases such as Kamala and further indulging nidana may lead to yakrit arbuda.

Pesticide exposure is one of the environmental factors hypothesized to increase the risk of HCC.¹⁵

Madyavarga: Madya (Alcohol) is considered as Pitta and Rakta Prakopaka as they are Ushna, Teekshna, Vidahi and drava leading to Arbuda.

Long-term alcohol use has been linked to an increased risk of liver cancer. Regular, heavy alcohol use can damage the liver, leading to inflammation and scarring. This might raise the risk of liver cancer.¹⁶

Amla, Katu Rasa ashana, Dadhi sevana, Vidahi ahara sevana:When taken in excess quantity for longer periods, it causes Pitta vriddhi, vitiates Rakta, Mamsa leading to arbuda in yakrit.

1. Viruddhahara as nidana

Those ahara (foods) which are deha dhatupratyaneekabhuta (antagonistic to body) are considered as virruddha. Eighteen types of viruddha are mentioned in Charaka samhita. These viruddhara can lead to inflammation at molecular level.

Viruddha bhojana further leads to agnidushti (vitiation of digestive fire) and formation of ama (toxic metabolites), which is visha roopi (toxic by nature) and leads to various types of dosha prakopa (increases dosha).¹⁷

Acharya Charaka in Atreya Bhadrakapiya, mentions Shotha as one of the diseases produced by the consumption of viruddhara.

1. Garavisha and Dushivisha

 Yogaratnakara explained that the Garavisha consumption shows its impact on the body by manifestation of symptoms like Lazyness, Heaviness, Cough, Dyspnea, Loss of strength, Haemorrhage, Edema and Yellowish discoloration of eyes. Hence,Garavisha and Dushivisha can be considered as nidana for Arbuda in Yakrit.

Food processing, additives and contaminants may also lead to cancer

Many substances are added to foods to prolong shelf and storage life and to enhance color, flavor, and texture. The possible role of food additives in cancer risk is an area of great public interest. Some of these compounds are not known to directly cause cancer, but they may influence cancer risk in other ways – for example, by acting as hormone - like substances in the body.

I. Shrotodushti nidana

Excessive consumption of ahara (food substances) having properties like guru (heavy), atisnigdha (uncutuous), abhishyanda (deliquescent), ushna (hot), vidahi (irritating food substances), varuni sevana (Alcohol), andvihaara like atichintana (over-worry), sevana of atapa (excessive exposure to sun) divaswapna (daysleep), all lead to dusti of Rasa, Rakta and Mamsa leading to Arbuda.¹⁸

Alcohol associated with Hepatocellular carcinoma¹⁹ 

The spectrum of hepatic injury caused by alcohol ranges from clinically insignificant or biochemical damage, to alcoholic hepatitis, fatty liver, and all the way up to cirrhosis. 

Polymorphism of the gene encoding for CD14 expressed on a Kupffer cell has been implicated in the risk of ALD and HCC.

II. Adibhautika Factors as Nidana

Disease caused by external factors like bhuta (microorganism), prani (wild animals) is called Adhibhautika vyadhi (disease due to external objects). It includes Sanghatabala privritta vyadhi.

Sanghatabala pravritta as nidana for Arbuda

Sanghatabala pravritta are such nidanas which causes agantu vyadhi (disease caused by external factors), that is vyadhi which is occurring due to external injury.²⁰  

Acharya Sushruta mentions Mushti praharadi (hit with fist)as one among the nidana for Arbuda to occur. When the place on the body is hit by fist etc and who takes Mamsa (flesh)continuously, develops painless, unctuous, stone like, non-movable swelling termed as Mamsa Arbuda.²¹ 

If the injury takes place at the level of Yakrit (liver), then it can be considered as Yakrit arbuda.

Term injury refers to break down of natural continuity of any tissue of the living body.

Different types of injuriesoccurs in day to day life such as physical, chemical, mechanical injuries.

Chemical Carcinogens²²

Cancer by chemical carcinogens occurs after a delay- weeks to month based on dose and mode of administration of carcinogenic chemical, individual susceptibility and various predisposing factors. Basic mechanism of chemical carcinogenesis is by induction of mutation in the proto – oncogens and anti oncogens. The phenomena of cellular transformation by chemical carcinogens is also progressive- a process involving 3 sequential stages- initiation of carcinogens, promotion of carcinogens, progression of carcinogens.

III. Adidaivika Factors as Nidana

The diseases which are produced due to nidanas that are beyond man’s control or influence and which occur irrespective of human activity, are considered as Adidaivika nidana (diseases caused by super natural agencies). 

They are divided into -

a. Kala bala privritta as nidana for Arbuda

These are diseases evolving out of variation in various seasons like rainy season, summer, winter. Diseases may arise from normal as well as abnormal seasons. Kalabala pravrita vyadhis are Jadya, Daha, Kampa, Vrana, Jwara and the term adaya (etc) is mentioned; hence, Arbuda in yakrit can also considered under this.

It is again divided into two kinds i.e Vyapannartukrta (abnormal seasons) and avyapanartukrta (normal seasons).

Avyapana rtukrita vyadhis are those in which season is not deranged, the herbs grow unaffected and water is free from contamination. The diseases originating in this rtu are due to seasonal variations affecting the doshas and causing its vitiation. The disease occurring in this rtu are self-limiting in nature. Hence, remedies described in particular rtu should be used for treatment purpose.

Vyapanna rtukrita vyadhis are the conditions manifested due to deranged seasons i.e, diseases arises due to abnormal cold, heat, air, rains etc. Abnormal seasons may trigger different type of psychosomatic disorders and can result in vyadhi. It requires independent disease treatments along with seasonal treatments. This avyapanna rtu may disturb the quality of basic human needs such as quality of soil, water and air. By repeated rtu vyapat (seasonal derangements), quality of basic needs are disturbed and may trigger the production of diseases like Yakrit arbuda.

This kind of nidanas are explained as Sadharana Nidana (those causative factors are common to living beings in general) under Janapadodwasa (Epidemics).

Population of a small West African country known as Gambia were exposed to Aflatoxin, which is well documented. Higher AFB1 exposure period is from October to March. Seasonal variation is positive for R249S TP53 Mutation in CFDNA; may constitute a biomarker of exposure or a predictor of liver cancer, depending upon the temporal variation.

Seasonal variation might affect the levels of contamination due to Aflatoxin exposure, which is again an etiology for causing Hepatocellular carcinoma.²³

Thus, we have to consider Kalabala pravritta as nidana in the manifestation of Hepatocellular Carcinoma.

b. Daiva bala privritta as nidana for Arbuda The diseases which are produced by causes that are beyond man’s control or influence and which occur irrespective of human activity.²⁴ Diseases produced by supernatural powers is termed as Daivabalprivritta vyadhi.

Involvement in social relationships has been associated with specific health conditions as well as biological markers indicating risk of preclinical conditions. Several recent review articles provide consistent and compelling evidence linking a low quantity or quality of social ties with a host of conditions, including development and progression of Cardiovascular disease, recurrent Myocardial Infarction, Atherosclerosis, Autonomic dysregulation, High blood pressure, Cancer.

Social life can induce stress leading to cancer and vice versa.²⁵  

Daivabala privritta is divided into two types i.e.Vidhyudasani krita (produced by lightning) and pisacadi krta (demons). Again, subdivided into Samsargaja (contagious) and Akasmika (suddenly, without notice).²⁶

Vidyutashanikrita is caused by natural calamities like thunder, lightning, volcanoes, floods etc. Sudden climatic changes due to natural calamities have a serious impact on human health, by increasing the incidence of number of diseases.

Different types of radiation act as mutagen when delivered in sufficient quantities. Any of these mutations may provide the subsoil for the development of cancerlater.

Specific studies related to natural calamities in relation with Hepatocellular carcinoma are not available.

Upasargaja vyadhis /Pishachadi krita vyadhis are those manifested due to evil spirits or due to close association with diseased persons.  

Here, evil spirits can be correlated with infectious organisms responsible for inducing cancer.

Hepatitis B virus is an important causative factor for inducing Hepatocellular carcinoma. Hence, Upasargaja / Pischachadikrita can be considered as one of the nidana for inducing Hepatocellular carcinoma.²⁷

Samsargaja act as nidana, if a person is residing with another person who is cursed by almighty god. i.e. because of Devadi droha. 

According to commentators, devadi droha is the condition where a person is Abhishapta i.e. cursed. It may lead to several diseases, which might influence nearby person residing along with him.

Here, we can correlate the term Abhishapta with effect of high pitch sound. Sound can affect physical and psychological health, which further induces stress, which may further influence carcinogenic process. However, the effect of sound in inducing Hepatocellular carcinoma is not clear. 

Akasmika nidana is such that, if a disease occurs all of a sudden without any apparent cause. 

Hepatocellular carcinoma in an individual having none of the risk factors mentioned above are considered as Idiopathic Hepatocellular Carcinoma.

c. Swabhava bala privritta as nidana for Arbuda

Ksut (hunger), Pipasa (thirst), Nidra (sleep), Jara (ageing, senility), Marana (death) affecting all individuals, are essential parts of life process itself. They are unavoidable. These are again of two kinds-Kalakritahappening at proper time and Akalakrita – happening at improper time, either early or late.

Kalakrita is Parirakshanakrita (caused by protecting the body with suitable food, activities etc.) and Akalakrita is Aparirakshanakrita caused by neglecting the protection of the body, by indulging in unsuitable foods, activities etc.

Age is the biggest single risk factor for cancer. There is no single explanation why an aging body is more susceptible to cancers. In addition, changes in tissues and organs with advancing age renders cells’ microenvironment more favorable to the development of cancer. The full picture of how aging and cancer are intertwined is still a work in progress. Many cancers are linked to unhealthy lifestyle at younger age, such as eating unhealthy diet, being overweight, alcohol, stress etc. which causes damage to cells leading to provocation of cellular mutation, thus leading to the genesis of cancer.²⁸

Hepatocellular carcinoma can be considered as one among them.

Conclusion

In ancient Ayurvedic literature, knowledge regarding malignant like disease was well known.We cannot find any specific reference by the name of Yakrit arbuda in our classics.

Liver tumors or Hepatic tumors are tumors or growth on or in the liver. These growths can be Malignant or Benign. The most frequent primary malignancy in liver is Hepatocellular carcinoma.

In our classics, we cannot get direct reference regarding yakrit vriddhi. Splenic and Liver enlargement takes place either due to Chyuta vriddi or displacement or by Achyuta vriddi signifying quantitative increase in dusta Rakta.   

Quantitative increase of Rakta dhatu may take place either due to disease pertaining to Rasa dhatu or due to Rakta dhatus. Acharya Chakrapani has stated the vriddhi of Mamsa dhatu also.  

In Ayurvedic literature, terms such as Gulma, Granti, Arbuda are used for specific tumor conditions. Various Ahara, vihara, shareerika and manasika hetus contribute to the formation of Arbuda in general and even in the liver. These nidanas can be further classified and understood through Adhyatmika, Adidaivika and Adiboutika nidanas responsible for causing Arbuda in Yakrit.

As there is no specific reference for Yakrit arbuda in our classics, it can be understood under the heading of Avastabheda of different vyadhis mentioned in classics with their respective etiopathogenesis. Here, an attempt was made to understand Samuthanavisesha of Arbuda in Yakrit w.s.r Hepatocelluar carcinoma in an Ayurvedic framework, to enrich the scope of Ayurveda in the preventive and curative management of HCC.