Colorectal neoplasm is one of the commoner forms of malignant disease; according to the Annual Report Registrar General, 1970 its incidence in England and Wales is second only to that of lung cancer. A survey of the hundred and seventy three patients documented in the Malta Tumour Registry as suffering from colorectal neoplasms between the years 1969-1972 (inclusive) was carried out. Several findings emanate from this survey such as the incidence in the younger age group, the presence of significant nausea and vomiting in fifty percent of the patients of the left hemicolon and twenty percent of cases with a tumour in the right hemicolon. Moreover, this survey has shown that there is an average delay of about six months from the time the patient first presents to his own practitioner until his hospitalization for investigation with yet further delays before surgery is attempted.peer-reviewe

Busuttil, Anthony

Carachi, R.

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3 THE INCIDENCE OF COLORECTAL TUMOURS IN THE MALTESE ISLANDS R CARACHI M.D. Senior House Officer, Pathology Department, Western Infirmary, Glasgow. A. BUSUTTIL M.D., M.R.e.Path. Lectu,fler in F,atholigy, Pathology Department, Western Infirmary, Glasgow. Colorectal neoplasm is one of the commoner forms of malignant disease; its incidence in England and Wales is second only to that of lung cancer (An-nual Report Registrar General 1970). The morbidity due to th:s tumour shows a marked variation throughout the world (Table 1). It appears from the figures available for study that countrIes with a higher socio-economic status, and a better distribution of medical services have a higher incidence than other less affluent countries. In Poland eight per hundred thousand of the population are affected by this tumour; in contrast the incidence for the province of Manitoba with a much smaller population is five fold higher. In spite of this, th:s tumour accounts for a s:zeable mOIltality in most areas. To date the incidence of such tumours in the Maltese Islands has not been formally studied. A survey of the hundred and seventy three patients documented in the Tumour Registry as suffering from colorectal neoplasms be-tween the years 1969-1972 (inclusive) was carried out. The local recorded incidence of colonic tumours is shown in figure one, and that for rectal tumours in figure two. The mean age of diagnosis of colorectal tumours was sixty years of age. Of particul-ar interest in this survey is the incidence in the younger age group (i.e. those below forty five years of age). These patients numbered twenty four and their ages ranged from twenty to forty five years. There is a great variation in the mor-bidity of colorectal tumours recorded in dif-ferent countries. In Table 1, an attempt has been made to compare the incidence of these tumours in our blands with that of other countries. It is well known that a number of morbId anatomical les~ons predispose to malignancy of the large intestne. There were only four recorded cases of adenomas in the survey, one of which was a two centimetre sessile adenoma; in spite of local excision this patient eventually died of extensive metastases. Some fam]les are unduly prone to develop carcinoma of the colon (lVlcSherry et a/ 1969). In th's survey two patients stated that their parents died of a carcinoma of the colon. Carriers of the trait of familial polyposis will invariably go on to develop cancer. Nine cases of fami!" al polyposis were found, six of whom already had a carcinoma supervening. Longstanding colonic inflammation may also be complicated by the develop-ment of carcinoma of the colon and rectum. In the survey there were two cases of cancer complicating ulcer&i;ve colitis. One patient had a multifocal adenocarc~noma with secondary metastases, at the age of thirty three years, the other had a recto-sigmoid tumour with a caecal fistula at the age of seventy two years. Both these cases 4 TABLE 1 Age/sex inc:dence of colorectal tumours compared with other countries Country Popu3ation ca. COLON morbidity ca. RECTUM morbid:ty in m;.:!ons Ma:e Fema:e Total Ma:e Fema;e Total /100,000 /100,000 Malta 0.32 4.0 4.4 4.2 3.5 2.0 2.8 1972 Alberta 0.80 14.3 17.7 16.0 9.3 7.5 8.4 1968 British Columbia 1.10 1968 23.0 22.9 23.0 15.9 10.7 13.4 Manitoba 0.76 28.7 33.5 1968 31.1 15.2 8.5 11.8 N. Branswick 0.50 27.4 31.2 1968 29.3 19.8 10.3 15.1 Prince Edward Island 0.10 14.4 34.9 1968 24.5 10.8 3.7 7.3 Quebec 0.18 15.5 19.7 17.6 10.2 7.5 8.8 1968 Saskatchewan 0.86 29.6 24.7 1968 27.2 14.9 8.7 11.9 Connetcut 2.0 20.4 14.4 17.3 4.3 5.0 4.7 1968 Israel 0.8 9.9 9.1 9.5 7.5 8.0 7.8 1967 Bulgaria 7.0 5.0 5.9 5.4 6.6 5.5 6.0 1968 Finland 3.9 7.2 10.2 8.8 6.7 9.5 8.2 1967 Hungary 9.2 7.0 8.6 7.9 10.0 6.9 8.4 1969 The Hague. 0.6 16.9 19.3 18.2 13.8 10.3 12.0 1969 Rotterdam 0.66 18.7 27.8 23.3 17.5 12.0 14.7 1969 Poland 24.0 4.0 4.4 4.2 4.2 3.9 4.0 1968 Sweden 6.9 24.1 26.5 25.3 17.1 12.1 14.6 1967 U.K. 43.0 18.1 24.2 21.3 16.4 12.5 :.~"""'I 14.4 1968 Yugoslavia 15.8 5.6 7.0 6.3 12.8 10.0 11.4 1969 5 had severe colitic symptoms of several years duration. Histogram to show the sex incidence in carcinoma In only one hundred and eight cases of the colon was histology of the tumours available; the rest of the cases had a clinical No of a di . d tIt d . c ses agnos"s ma e a a aparo omy an nec-ropsy confirmation was singularly lacklng. 15 " MALE TABLE 2 Histological Classification Histological types 1. Adenocarcinoma 2. Argentaffin carcinoma 3. Leiomyosarcoma 4. Malignant lymphoma Number of cases 104 2 1 1 Ninety five per cent of the tumours were carcinomas of variable degrees of ddferentiation. Both cases of argentaffIn carcinomas died from metastases. A twenty three year old had a carcinoid tumour in the pelv~c colon, and a sixty seven year old had an argentafLn carcillo-ma of the ascending colon. Neither had any clinical evidence of the carcinoid syndrom~. The distribution of these tumours in the large bowel is shown in figure three. Tbe tumours in the rectum w 2re equally d:stributed in the lower th:rd of the rectum, the ampulla, and the upper third rectosigmoid colon. Sixty five per cent of the tumours occurred in the rectum, a place easily ac-cessible to investigation, namely palpation and endoscopy. The next commonest site for a carcinoma of the colon was thJ caecal region, which constituted sixteen per cent of all the tumours recorded. Th:; other twenty per cent of tumours were equally d:strib'1.bd over the rest of th3 colon. The classical way in which these tumours are said to present is a history of recent gross change in bowel habit, bleed-ing per rectum, weight loss and/or symptoms of dramatic large bowel obstruc-tion. In the cases, reviewed, this could be no further from the truth. The commonest mode of presentat;on was lower abdominal pain. Overt bleeding was reported by about half the patients with tumours of the sigmoid colon; with the other colonic FEMALE 1969 1970 1971 1972 Years Figure 1 tumours ble2ding occurred in less than a third of the patients, also infrequent were the changes in bowel habit. An interesting find:ng was the pre-sence of significant nausea and vomiting in fifty per cent of the patients with tumours of the left hemicolon and twenty Der cent of cases with a tumour in the rigiit hemi-colon. This was associated with - anorex'a in a number of these patients. In some of the cases, investigation for an UDDer gastro-intestinal tract lesion had already been in progress for some time thus delaying the diagnosis considerably. Ep:'sodes of acute obstruction super~mposed on chronic Histogram to show the sex incidence carcinoma of the rectum No. of cases 15 5 10 15 MALE; FEMALE 1969 1970 1971 1972 Years Figure 2 obstruction occurred in a quarter of the patients with sigmoid tumours. In tumours of other parts of the colon, obstruction only occurred as a late manifestation. Another mterestmg observation was the presence of a pyreXla as one of the presenting features in a number of the tumours and some of these patients had undergone lengthy serological,- radiological and bacteriological investigation for their pyrexia. Ulceration of the tumour, subse-quent infection with endogenous coliform organisms and endotoxin absorption would account for the fever in such cases. Pallor and the laboratory evidence of a m~crocytic hypochromic iron deficiency anaemia was another important clinical sign. The presence of associated bleeding haemorrho_ds in such cases could be taken as a possible cause for the anaemia and this happened in two cases on record. The presence of complicated diverticular disease is yet another plausible explanation for abdominal pain, obstruction, bowel habjt alteration and bleeding, and th~s may act as yet another red h~rrlng in the pre-sence of a coexIsting noeplasm: this oc-curred in six of the cases significantly de-laing the diagnosis. Four cases presented as an emergency with a picture of an acute append.citis be-cause of nausea, vom~ting and abdominal pain. At laparotomy a tumour was dis-covered in the caecum and had caused the obstruction of the lumen of the appendix. TABLE 3 Percentage incidence of Symptoms and SIgns Symptoms and Right colo ~ic Left colonic Sigmo:d Rectal signs tumours tumours tumours tumours Abdominal pain 68 62 52 24 Bowel complaints 30 25 50 54 Bleeding 20 31 55 64 Vomiting and Nausea 27 50 ? ? Anorexia 6 12 ? ? Mucus in stools 2 2 4 Tenesmus 6 2 9 Palpable abdominal mass 54 25 Anaemia (Pallor) 34 6 12 4 Pyrexia 4 18 5 Mass felt P.R./endoscopy 20 100 Acute obstruction 9 18 25 1 Diagram to demonstrate tumor incidence in different parts of the caecum, colon and rectum Figure 3 In all the tumours of the rectum re-corded, a palpable mass was present. Bleeding occurred in almost two thirds of these cases in association with a change in bowel habit. The negative find:ng of a lack of alteration in bowel habit of about a half of the patients with such tumours was worth serious consideration. Also particul-arly significant were the absence of com-plaints of tenesmus and mucus admixed with the stools, both of which are popularly taught to be important diagnostic signs. Pain was also a late feature in rectal car-cinoma, though ultimately it might give rise to great distress. There was an average delay of six months from the onset of symptoms to hospitalization. Discussion Over the past decada an increase in the incidence of colonic cancer has been recorded, but with no corresponding elevated incidence of rectal neoplasms (Stewart 1971). The inc'dence also appears to differ among countries. Both these features have led to epidemiological spe-culation as to its aetiology, with the diet coming under suspicion, as one of the fact-ors responsible. Colonic tumours especial-7 ly those of the r;ght hemicolon often re-quire radiological investigation which may not be universally available, and the inter country variatio:1 may just reflect the availability and the sophist'cation of the mzdical services prov·ded. This alone does not fully explain the discrepancies in in-cidences. Burkitt (1971) related the occurrence of tumours of the large intest:ne to diet on a goegraphical basis. Diets which are h:gh-ly processed and refined and therefora de-ficient in fibre content are consumed in areas of a high incid<>nce of coloreCtal can-cer. Aries et- al (1969) have shown that there is a striking var' ation in the bacterial flora in relation to the diet content. Hill et al (1971) proved that intestinal bacteria degrade bile salts differently and that the Bacteroides species among others, which are particularly abundant in the stools of individuals on a fibre-deficient diet can break down bile salts to possible colonic carcinogens. Recently beef consumption has been correlated with large bowel cancer (Haenszel et af 1974). The occurence of large bowel tumours in our Islands is very low in comparison w'th other count-ries in Europe (Table 1). Various explan-ations for this are possible, unfortunately no figures as to consumption per carpita of the type of foods under sus!lici.on are avail-able from our Islands for comparison with those of countries with a h'gh tumour in-cidence. It would be indeed interesting to carry out a prospective survey. looking into the dietary habits of the population and the faecal flora and attempt to correlate it with the 'low' incid?nc" of rolorectal carc;-noma in the Maltese Islanos. Precancerous states of the colon were well represented in thlS survey. Polvpo'dal If>sions of the lan~e bowl7'l are no~oriously of sinister import.- Spratt et al (1971) pro-posed that elective sur~ical intervf>ntion and resect'on should be undertaken of any intraluminal mass larger than ten milli-metres seen either on barium studies or at endoscopy. This is interesting when one bears in mind that one of the casps re-vipwpd had a twpntv millimetre adenoma wh'ch was only locally resected and event-ually gave rise to extensive metastases. Macklin (1960) found that children of 8 parents with large intestinal cancer had a threefold increase in the expected date of colonic cancer and McSherry et al (1969) also conclusively showed that some fami-lies are unduly prone to develop carcinoma of the colon. Individuals w:th the 'familial polyposis' trait develop carcinoma of the colon as well and the tumour occurs in a much younger age group than is normally otherwise encountered. The incidence of this condition is said to be one in eight thousand three hundred births and is a do-minant gene of variable penetrance (Reed et aI1955). These, polyps are rarely seen be-fore the age of ten years; bleeding is sa:d to herald the malignant transform-at'on. The nine cases reported within the space of four years suggests a high inci-dence for our population and genetic counselling of these- families in danger is strongly indicated. Longstanding colonic inflammation as found in ulcerat~ve colitis and schistosomal infestation can be complicated by the de-velopment of carcinoma of the colon and rectum. There is general agreement that cancer supervenes in three to five per cent of ulcerative colitis cases (Morson, 1969). The latter patients would have had symptoms of the chl~onic continuous disease, with a total colonic involve-ment for more than ten years; the distal forms carry an almost insignific-ant risk factor. The c,mcers which do develop are multiple, more invasive and less differentiated and are associated with a worse prognos's (Morgan 1971). The risk factors mentioned above necessitate six monthly colorectal biopsies and barium studips in such uatients. Histochemic-al studies of carcinomas of the large bowel han revealed features of both prognostic and aetiological value. The enzymatic patterns wilthin the tumour cells become less specific as the tumour be-comes more and - more undifferentiated, and by an elaborate quantitative histoche-mical technique a working urognostic classifica,tion has been attempted (McGinty et aZ 1973). Mucosubstances produced by the neoplastic ep i thplium have also been s;milarly examined (Swbbuswamy 1972). In the secretions of the normal colonic muco-sa both sulphated and non-sulphated acid mucosubstances predominate. The muco-substances produced by s:mple tumours are predominantly acid and non-sulphated and carcinomas produce scanty secretions with little suJphation of the mucopolysaccha-rides. These mucosubstances might there-fore in some way regulate cell turnover and divis'on, and a decrease in the con-centration of sulphated mucopolysaccha-rides in bowel mucosal secret' on may precede the actual development of the tumour. Mucosubstances are decreased in ulcerative colitis and are mainly non-sul-phated acid in type but not in Crohn's disease, and the differ'ng proneness to malignancy of these two- diseases adds weight to the argument. The technical expertise involved in the study of these substances precludes their use as a routine procedure. -Over the last few years oncofoetal antigens, namely antigens present in foetal life but which normally disa.ppear in extra-ut~rlne life until a tumour develops, han come to the forefront as possible early d' agnostic aids for cancer. The carcinoem-bryonic antigen (C.E.A.) has been the most promising in this respect. S:nce Gold and Freedman (Thomson et al 1969) pioneered the sensitive Radioimmunoassay -technique for th3 detection of this antigen extensive tesfng of large clinicaJ ser:es and controls has been undertaken in a number of centres (Miller et al 1974). The antigen is invariably present in concentrations ex-ceeding 2.5 na1Jograms uer millilitre in malignant large bowel tumours whether primary or secondary but may also be found in oth~r tumours mainlv of th~ fore-gut. haomopoef c SYSt::>ffi and from ectoder-mal origins. as well as in inflammatory conditions of th~ gastro-int~stinal tract. al-cobolic cirrhosis and chronic pancreatitis (Laurence et rr} 19721. Its value as a screen-ing test has dimin'shed (Miller et a/ 1974). Its use as a monitor of s3condary tumour d3VE'lopm::nt is mori'\ urcmising, and in a number of Ca3€S th" development of hepatic metastases could be predicted from several estimations of C.E.A. This would allow for an early radicql a,uuroach to thos3 tumours. Attempts at refining the estim-ation by making th3 assay more selective (Simmons et af 1973) may further increase the diagnostic value of this test. This survey has shown that there is an average delay of about six months from th2 t~me the patient first presents to his own practitioner until his hospital"zation for in-vestigation with yet further delays befor2 surgery is attempted. The apparent cause for this is that -all too of ten- the patient presents with 'vague symptoms'; the class-ical textbook clinical picture appears much too late. Pa;n of anv type is a particularly late symptom. In this respect 'piles' and colonic diverticular disease are often in-voked as the cause of changes in bowel habit. gastro~intestinal upsets, anaemia and even bleeding per rectum in the middle-aged patient. Med:ccl.l therapy is usually in-stituted for a few months, and the patient is only investigated when this has failed. Keeping in mind that the vast majority of large bowel tumours develop within the last twenty five centimetres of the large bowel, digital rectal examination and proctosigmo'idoscopy will diagnose these neoplasms. Radiologv of the large gut ;s also straightforward; the recent application of double contrast enemas have greatly im-proved the accuracy of diagnosis with special reference to polypoidal lesions and cancers of the right hemicolon (Martel 1971). A~knowled,g~ment We would like to acknowlodge th~ hp-Ip of Professor V.G. Griffiths and Dr. Sultana for allowing us to collect these cases from the tumour reg'stry of Malta. Refp.r"nces 1. ARIES. V., CROWTHER. .T.S .. DRASAR, B.S., HILL. M.J., WILLIAMS, R.E.O. (1969) Gut, 10, 334. 9 2. BDRKITT, D.P. (1971) Cancer, 28, 3. 3. HAENSZEL, W. BERG, J.W." SEGI, M. KDRIHARA, M., LOCKE, F.B. (1974) J. Natl. Cancer Inst., 51, 1765. 4. HILL, M.J., DRASAR, E.S., ARIES, V.C., CROWTHER, J.S., HA WKSWORTH, G.M., WILLIAMS R.E.O. (1971) Lancet i, 95. 5. LADRENCE, D.J.R., STEVENS, D., BET-TECHEIM, R., DARCY, D., LEESE, C., TURBERVILLE, C., ALEXANDER, P., JOHNS, W.E., MDNRO NEVILLE, A. (1972) British Medical Journal Vol. 3, 603. 6. MACKLIN, M.T., (1960) J. Nat. Cancer lnst. 24:551. 7. MORGAN, C.N. (1971) Cancer 28, 41. 8. McGINTY, F., DELIDES, G., HARRISON, D., (1973) Gut, 14:502. 9. McSHERRY, C.K., CORNELL, G.N., GLENN, F. (1969) Annals of Surgery, 502. 10. MILLER, A.B., (1974) Cancer, 34:932. 11. MORSON, B.C., (1969) British Journal of Hosp.ital Medicine. 1839 (Nov.). 12. REED, J.E., NEEL (1955) Amer. J. Hum. Genet., 7:236. 13. Registrat General's Statistical Review of England and Wales (1970). 14. SDBBDSWAMY, S.G. (1972), Gut, 12:200. 15. SIMMONS, D.A.R., PERLMANN, P., (1973) Cancer Res., 33:313. 16. SPRATT, J.S., WATSON, F.R., (1971) Cancer 28:153. 17. STEWART, H.L., (1971). Cancer, 28, 25. 18. THOMSON, D.M.P., KRUPEY, J., FREED-MAN, S.O., and GOLD, P. (1969). Proceed-ings of the National Academy of Sciences, 64, 161. 19. WORLD HEALTH STATISTICS REPORT, Vol. 25 No. 5 (1972). 20. MftRTEL, W., ROBINS, J.M., (1971) Cancer, Vol. 28, 137. 

The incidence of colorectal tumours in the Maltese islands

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The incidence of colorectal tumours in the Maltese islands

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