Tumours and cancers in Graeco-Roman times TUMOURS AND CANCERS IN GRAECO-ROMAN TIMES ABSTRACT In Graeco-Roman times all tumours (Greek: onkoi, abnormal swellings) were consi- dered to be of inflammatory origin, the result of unfavourable humoural fluxes, and caused by an extravascular outpouring of fluid into tissue spaces. The neoplastic nature of tumours is a more recent concept, barely two centuries old. In Hippocratic litera- ture tumours were mainly classified as karkinômata, phumataand oidêmata. Phumata included a large variety of tumours, inflammatory and neoplastic in origin, and mostly benign (in modern terms), whilst oidêmatawere soft, painless tumours and even includ- ed generalised oedema (dropsy). Although all categories possibly included occasional cancers, the vast majority of what appears to have been malignant tumours were called karkinoi/karkinômata(Latin: cancrum/carcinoma). There was however no recognition of benign and malignant, or primary and secondary tumours, in the modern sense. 1. INTRODUCTION Herodotus tells us that at the turn of the 6thcentury BC, Atossa, the wife of Darius the Great, was cured of a breast tumour (phuma) by a captive Greek physician, Democedes.1L.J. Rather (1978:8-10) suggests that the readiness with which Democedes promised a cure and the ease with which he attained this, points at a benign breast tumourrather than a cancer. The Hippocratic writings mention a woman fromAbdera who had a breast tumour and a bloody discharge from the nipple, was diag- nosed as having a karkinôma, and died of the lesion.2This was most likely a cancer as we know it today. However, the Graeco-Roman theories of tumour formation and carcinogenesis differed radically from our mo- dern concepts which originated as late as the 19thcentury. In the present study the theories of tumour formation in antiquity and the nature of tumours reported are reviewed. 1 HistoriesIII.133-4. 2 EpidemicsV.101. 200 Acta Theologica Supplementum 7 2005 2. THEORIES OF TUMOUR FORMATION In antiquity all tumours were considered to be of inflammatory origin and explained with reference to the humoural theory, in vogue since early Greek times (Rather 1978:12-13). According to Celsus’s clas- sical description, inflammation was characterised by pain (dolor), redness (rubor), heat (calor) and swelling (tumor). However, pain, redness and heat were gradually restricted to “exquisite inflammation” near a body surface, while tumor was accepted as indicative of nothing more than an abnormal swelling or mass (still caused by inflammatio). This re- mained dogma as late as the 18th century (Rather 1978:26). According to the humoural theory all matter originated from four universal elements: fire, air, water and earth. These elements were brought into relation with four basic qualities (dunameis): hot, cold, moist and dry. The Hippocratic writers associated these dunameiswith their four bodily humours: phlegm, blood, black bile and yellowbile. The precise associations fluctuated with time, but were eventually fi- nalised by Galen and then remained unchanged for 1500 years: blood was associated with hot and moist (air, spring), phlegm with cold and moist (water, winter), yellow bile with hot and dry (fire, summer), and black bile with cold and dry (earth, autumn). According to Galen, perfect health depended on the right mixture (eukrasis) of hot, moist, cold and dry, and illness was caused by an imperfect balance (duskrasis). The humours originated from ingested food. Through a process fa- cilitated by cooking (pepsisin Greek, concoctioin Latin), digestion and subsequent maturation in blood vessels and body tissues (under influ- ence of predominantly innate body heat), the humours evolved. Di- gested food (chulê) was absorbed into the portal vein and liver where yellow bile (cholê) was formed. The earthy, cold components of nutri- ment were converted to black bile (melaina cholê) by the spleen to streng- then the body fibres. Blood was the most important humour and phlegm was mainly a waste product. The circulatory system (nourishing the body parts) consisted of ar- teries (which carried heat and pneumaor spirit, derived from inhaled air) and veins (which conveyed blood, as well as the other three humours in varying mixtures depending on local or systemic circumstances). Between arteries and veins were specialised anastomoseswhich only opened 201 Tumours and cancers in Graeco-Roman times under certain abnormal conditions, e.g. fevers or trauma, pouring blood into arteries with resultant regional congestion, and interference with peripheral delivery of pneuma. Venesection allegedly alleviated this. Galen later showed that arteries did contain blood and not air, but this did not cause him to change his views on inflammation. Galen postulated that moist inflammation, inter aliaresponsible for tumour formation, arose from a “flux of humours”. This entailed an abnormal congestion and mixture of these substances in response to stimuli like fever, injury, fractures and over-exertion in a localised region of the body. Depending on the humoural mixtures, the type of inflam- matory response would differ, e.g. with excessive yellow bile herpes developed, erysipelas was caused by very hot bile, anthrax arose from thick hot blood, and an oidêmafrom excess phlegm. A flux of blood and black bile caused scirrhus, capable of converting into cancer (karkinos). Black bile unmixed with blood caused karkinoi, most often in the fe- male breast. Galen also postulated a rare form of dry inflammation, when only heat and no humour flowed to a bodily part. Then tumour formation was impossible. Tumours thus arose from localised inflammation when flux caused exudation of fluid from the veins into the fleshy (sarks) or parenchymal components of the body part (parenchuma). This happened because the tissues had acquired an abnormal ability to extract fluid, or because an abnormal mix of intravascular humours facilitated the extravasation of fluid. Accumulated extravascular fluid could be broken down (diaph- theretai) to form a fully concocted mixture (materia peccans) which was either gradually absorbed, discharged as septic residue (abscess), or remained indefinitely as a tumour which could have various charac- teristics. Soranus3used the word onkosto cover all tumours whatever the nature. In the Hippocratic writings there is reference to various kinds of tumours: 1. Karkinos, karkinôma(Latin: cancrum, carcinoma). Although not always indicative of cancer as we know it, many of the reported cases4pro- 3 GynecologyIII.35 and 36. 4 Epid.V.101; VII.111; AphorismsII.15; VI.7, 38; VII.8; Ancient Medicine22.60. 202 Acta Theologica Supplementum 7 2005 bably do represent cancer. The name is derived from the Greek for “crab” because of a fancied resemblance of the tumour to this ani- mal with its hard and rough exterior, and its long projections (feet and claws) into the tissues, onto which it adheres tenaciously (Rather 1978:16). The verb karkinoôrefers to the process of converting to cancer and was used with reference to cancerous changein certain lesions of the female genitalia (Rather 1978:9-10). 2. Phuma.5An inclusive term which encompassed a great variety of predominantly non-malignant and inflammatory tumours. 3. Oidêma.6A soft, usually non-tender tumour, sometimes pitting on pressure. It probably included gross oedema of the body. Other terms for tumours, less often used in ancient literature, in- cluded scirrhus, struma, melicerides, condyloma, tuberculum, occalescit, and carcinode.7 3. TUMOURS DESCRIBED IN LITERATURE 3.1 Karkinos, karkinôma When Hippocrates (5thcentury BC) states in the Aphorismsthat it is better not to treat internal cancers as this shortens life, the term karkinos is used.8 As mentioned above, this term is also used regarding the woman from Abdera who died of a breast tumour which presented with a bloody discharge from the nipple. In the Epidemicsa patient is described with a karkinôma of the pharynx which was cured by cautery.9 This is perhaps less likely to have been a true cancer in the modern sense. Retsas (1986:42-5) claims that a Hippocratic work, On carcinosis, was mentioned by Bacchius in the 2ndcentury BC, but no longer survives. Cato the Elder (234-149 BC), the inveterate proponent of cabbage as a panacea for illnesses, claimed that a cabbage poultice will heal 5 Aph.VII.8; Glands17; Epid.II.1.7. 6 Airs, waters and placesVII.30; PrognosticVII.10; Aph.VI.7; VII.8. 7 Celsus, De MedicinaII.1.19; V.18.5, 23 and 26; VII.14.1; Galen, De tumoribus praeter naturamK.VII c.9; Soranus, Gyn.IV.4. 8 Aph.VI.38. 9 Hipp. Epid.VII.111. 203 Tumours and cancers in Graeco-Roman times all kinds of ulcers and swellings, and in particular a carcinomaof the breast.10Celsus (1stcentury AD) also used the term carcinomato describe a strange ulcerating and incurable lesion of the upper part of the body, but which also involved the spleen. He mentions that the Greeks called it malignant (kakoêthes), but that it was impossible to distinguish between those lesions associated with rapid death and those with a long survival. In describing a progressive ulceration of the penis, Celsus uses the word cancrum. This might well have represented a true cancer, but he goes on to say that unless rapidly cauterised, it will develop into aphagedaena, a necrotising condition associated with blackening of the skin and total destruction of the organ.11Elsewhere, when dealing with surgical removal of urinary stones, he uses the word cancrumor cancer to describe a very serious complication of this procedure.12However, this almost certainly represents a rapidly spreading sepsis, even gan- grene, rather than a malignant tumour. Similarly his theriomaresembles necrotising ulceration rather than carcinoma. Galen (2ndcentury AD) recognised incipient cancers (karkinoi geno- menoi) and applied deadly nightshade (solanum nigrum) in the treatment of ulcerated cancers (hêlkêkoi karkinoi).13 He recognises a variety of hard ulcerating and non-ulcerating nodular lesions (karkinoi) of the breast, uterus, male and female genitalia and elsewhere which carried a bad prognosis unless properly treated. His treatment consisted of initial “emptying of melancholic humours” (through venesection) (Fig. 30). followed by surgery (complete resection of all vestiges of tumours) and supplementary topical and systemic remedies. He echoes Hippocrates in stating that only superficial cancers should be treated this way (Retsas 1986:48-52). Leonides, a contemporary of Galen, described total mastectomy for those cancers not attached to the thoracic wall (Retsas 1986:48-50). Retsas (1986:50-52) also lists Rufus (2nd century AD), Philumenis (2nd century), Oribasius (4th century), Aetius (6th century) and Paul of 10 On agriculture156.1-157.4. 11 Med. VI.18; V.28.2. 12 Ibid. V.18; V.28.2. 13 Ad Glauconem de medendi methodo II.12, K.XI.143; De simplicium facultatibus VIII.19, K XII.146. 204 Acta Theologica Supplementum 7 2005 Figure 30: Doctor performing venesection. Red figure vase, 5thcentury BC. Louvre Museum, Paris. Aegina (7thcentury) as physicians of antiquity who described lesions which could have been cancers. Dioscorides (1stcentury AD) recom- mended specific ointments for a karkinos, e.g. of the nose.14He used cantharidin against a tumour called karkinôdê, but Celsus refers to carcinode as a benign variety of phuma.15 14 Dioscorides, De Materia medicaII.12. 15 Med. V.18.23. 205 Tumours and cancers in Graeco-Roman times 3.2 Phuma/Phumata Under this heading were included a vast array of tumours ranging from minor skin nodules to large pelvic tumours obstructing labour. In the Hippocratic writings many of these tumours were quite non-specific and ill-defined. However, the urethral phumamentioned in Aphorisms IV.82 and internal phuma of Aphorisms VII.8 probably refer to infec- tive tumours, even abscesses. Scrofulous tumours referred to in Glands 7 were almost certainly of infective nature, as were the para-aortic tumours (possibly renal cysts or abscesses) associated with kidney stones in Nature of Man c.14. The abscesses and tumours (phumata) men- tioned in Ancient MedicineXXII.60 are of quite uncertain nature. The small mammary tumours (also called tubercles) associated with lac- tation, mentioned in Glands c.17 could have been fibroadenosis or innocent retention cysts — and one might speculate that Atossa’s breast tumour (phuma, mentioned above) could well have been an abscess or tumour of this nature. In his description of penile disease, Celsus refers to excrescences (phumata) appearing on the glans before cancrum sets in. He also de- scribed a variety of small skin tumours. Many would seem to be minor infective lesions, and apparently easily cured by local applications — among them meliceridis(favi) and carcinode.16Dioscorides17suggested colchicine applications for phumata not yet producing pus. Phumata empuawere suppurating lesions (possibly even tuberculous lymph nodes). Phumata sklêra were hard tumours in the breast which did not sup- purate, but became increasingly harder and could develop into karkinoi kruptoi (occult cancers) (Rather 1978:9-13). Soranus (2ndcentury AD) quotes Herophilus (3rdcentury BC) when he states that abscesses and tumours in the pelvis may obstruct labour. These non-specific tumours are also referred to as phumata.18 16 Ibid.V.18.20 and 23. 17 Mat. med. IV.84 18 Gyn. iv.4-5. 206 Acta Theologica Supplementum 7 2005 3.3 Oidêma When Hippocrates writes about swelling of the hypochondrium, he refers to a lesion which is soft, painless and pits on finger pressure, as oidêma— with a better prognosis than hard swellings, but nevertheless indicative of protracted illness.19Elsewhere, dropsy appearing in under- nourished persons is referred to as oidêmata, as well as pelvic tumours causing leucorrhoea in women. And when the causes of abdominal swel- lings (oidêmata) are discussed in the Aphorisms (VI.7), abdominal wall swellings are said to have a better prognosis than deep swellings. Dioscorides20recommends cabbage, colchicine in wine, or cucumber for soft swellings (oidêmata) without defining them. Galen is also vague about the exact nature of oidêmata, and seems to accept generalised dropsy as a manifestation of it, but does include it in the same cate- gory of tumours which could well have been malignant growths. He prescribed three specific herbs for the treatment of oidêmata.21 3.4 Other Galen defines skiros (scirrhus) as a hard and painless swelling which might arise spontaneously, develop in an area of inflammation (like erysipelas), or originate from an oidêma “when excessively cooled”. It couldgive rise to a karkinos.22The word strumaaccording to Galen23 refers to a hardening of lymph nodes, while Celsus uses the same word for scrofulous tumours (Latin: swollen neck glands), which might well have represented tuberculous lymphaderopathy.24Anal kondulômata (Greek for callous lump) were considered of infective origin although some kondulômatacould well have been malignant neoplasms.25Celsus usesthe Latin word occalescit(a hardening of the skin) to refer to a cal- losity of the penis; nasal polyps are described as carbunculae (Latin: fleshy protuberances), and gingival gumboils as parulides, while the term 19 Airs, waters and places7; Prognostic7; Aph. VI.7. 20 Mat. med. IV.84 and 150; II.121. 21 Ad Glauc. de med. meth. II.12, K.XI.143; De simpl. fac. VIII.19, K XII.146. 22 De tumoribusc. 9. 23 Ibid. c.15. 24 Med. V.28.7; V.18.13. 25 Ibid. VII.30. 207 Tumours and cancers in Graeco-Roman times tuberculumsimply signified a very small tumour.26The word kêriaoc- curring in the Hippocratic writings, has been translated as a malignant (Greek: deina) cyst.27 However, “malignant” does not necessarily carry the modern connotation as in malignant neoplasm. The original Greek words were deina(“fearful”, “terrible” in the sense of something which is to be regarded with awe because it passes human understanding) and kakoêthês(“malicious”, “abominable”), and referred to both infective and neoplastic lesions (in modern jargon). The Latin word vitiosa(meaning corrupt, vicious), used by Celsus, is also translated as malignant.28The Hippocratic AphorismVI.4 is usually translated as statingthat an ulcer with a pealing edge is malignant (Greek: kakoêthês). Theriomais often considered synonomous with malignancy but Celsus’s original descrip- tion29 fits in better with a very severe, spreading infection. 4. DISCUSSION In Graeco-Roman times the concept tumour (onkosin Galen’s termi- nology) embraced all abnormal swellings of the human body, and were explained on the basis of inflammation as understood within the hu- moural theory (Rather 1978:9-13). Abscesses and neoplasms (in the modern sense) thus simply represented different phases of the same inflammatory process. Tumours resulted from accumulation of extra- vascular fluid and not from overgrowth of body tissues (neoplasia, as first described in the 19th century) — and the concept of benign or malignant tumours was thus non-existent. As blood-letting (vene- section) was considered beneficial to relieve inflammatory congestion, it was considered efficacious for the treatment of all tumours. Similarly cautery, application of caustic substances and excision was random therapy for all superficial tumours, even severe ulceration. Extensive lists of local tumour applications are given by Dioscorides and others (Riddle 1985:319-330). 26 Celsus, Med. VI.18.8; VII.14.8. 27 ProrrheticII.32. 28 Celsus, Med. VII.14. 29 Med. V.28.3. 208 Acta Theologica Supplementum 7 2005 However, while phumaand oidêmaapplied to tumours which appa- rently were predominantly benign in the contemporary sense, it is clear that karkinos/karkinôma(fore-runner of our own word “cancer”) was re- cognised by the ancients as having a bad prognosis, often causing death. We cited reported cases of these lesions affecting the female breast and genitalia, the pharynx, penis, nose, “chronic ulcers”, “the upper part of the body”, and internal organs. Four chapters of Soranus’ Gynecology(Book IV.5-8) were devoted to tumours of the uterus, but are unfortunately lost to us. Galen warned that while it was possible to fully excise some super- ficial cancers (Retsas 1986:48-52), Hippocrates had said that cancers of internal organs should not be treated, as this shortened life,30and Celsus wrote that carcinomawere incurable.31He also found it impos- sible to predetermine which growths would respond to therapy.32Dio- scorides’s and Celsus’s carcinodewas probably a benign skin condition. The concept that a “benign” lesion could turn into a cancer is embodied in what Galen called “incipient cancer” (karkinos genomenos) as well as in the Hippocratic views that hard mammary growths (phumata sklêra) which did not suppurate, turned into occult cancers (karkinoi kruptoi), and that ulcers of the female genitalia, wrongly treated, became can- cerised (karkinothenai ta helkea) (Rather 1978:9-13). The ancients were thus aware of pre-malignant conditions. Celsus’s description of what possibly represents a penile cancer, ob- viously includes severe associated septic balanitis, infectious phumata of the glans and spreading phagedaena(a “tissue eating” process).33Celsus considered this part of the cancerous lesion, but it could as well have been the necrotising, gangrenous infection we today know as phagedena (usually seen in neglected or malnourished patients). His theriomacould likewise have been a phagedenic ulcer. The word “scirrhous” which today appears in the description of hard, sclerosing cancers, was also used by Galen to denote hard, painless swellings, some with malignant potential. Struma, today restricted to 30 Aph. VI.38. 31 Med. VI.18. 32 Med. V.28. 33 Med. VI.18.3-4. 209