1 Dipartimento di Medicine e Specialità Mediche, Medicina I and 2 Dipartimento di Anatomia Patologica e di Medicina Legale, Università di Modena e Reggio Emilia; 3 Dipartimento di Anatomia Patologica, Ospedale di Carpi (Modena), Italy
Received 23 January 2004; revised 4 February 2004; accepted 4 February 2004
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ABSTRACT |
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Two-thirds of colorectal malignancies are localised in the left colon and rectum. Recent studies suggest a trend towards an increase of right-sided tumours which might have important implications for screening and surveillance. A colorectal cancer registry was set up in Modena, northern Italy, with the purpose of examining incidence, subsite distribution and staging of colorectal malignancies over a 15-year period.
Patients and methods:
From 1984 to 1998, 2517 tumours in 2462 patients were detected and staged with the tumour node metastasis (TNM) system. The right colon was considered from caecum to splenic flexure; the left colon included descending and sigmoid colon; and the rectum included rectosigmoid junction, ampulla and anus.
Results:
Cancer incidence showed an overall increase. Considering the various subsites, an increase of 33.7% in all colonic segments was shown whereas rectal tumours tended to decline. TNM staging showed a gradual increase of localised lesions (41.2% in 1984 versus 53.3% in 1998), with a proportional reduction of advanced tumours.
Conclusions:
Our study indicates an increase of tumour incidence in all colonic segments more than a shift to the right colon. TNM staging tended to improve with an appreciable increase of localised lesions. These findings could be consequent to a more extensive use of colonoscopy.
Key words: cancer, colon, incidence, rectum, registry
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Introduction |
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Subsite distribution of colorectal malignancies indicates that ~70% of them are localised in the distal or left large bowel, i.e. between the splenic flexure and the lower rectum [6]. Several studies, however, showed a tendency for a proximal shift of cancer distribution, with right-sided lesions becoming more and left-sided lesions less prevalent [711], but not without controversies [1214]. It remains unclear if this is a true biological phenomenon or simply an artefact due to many reasons, including the lack of agreement on the most appropriate division of the colorectum into anatomical subsites [15, 16].
The debate is not only academic or theoretical, but may have important implications in the screening and surveillance of high-risk individuals. Indeed, it is usually assumedby traditional teachingthat >50% of colorectal tumours can be detected with the flexible sigmoidoscope [17, 18]. If the rightwards shift is a true phenomenon, this might represent one more argument for abandoning sigmoidoscopy and favouring pancolonoscopy as the technique of choice for screening individuals at risk of colorectal cancer. In a recent editorial [19] it has been stated that "relying on flexible sigmoidoscopy is as clinically logical as performing mammography of one breast to screen women for breast cancer".
A specialised colorectal cancer registry was instituted in the local health care district, in 1984 [20]. Through the data of this registry, we purposed to examine the pattern of incidence of these tumours, subsite distribution and staging over a 15-year period.
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Patients and methods |
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Registration of all colorectal malignancies that developed in the resident population began in 1984; by the end of 1998, 2517 tumours in 2462 patients (1298 men and 1164 women) had been detected. Histological verification was obtained in 98.0% of cases, with an average mortality/incidence ratio of 0.65. Colorectal tumours were classified according to the International Classification of Diseases for Oncology (ICD-O) [23]. Ambiguous or unclear definitionssuch as superficial cancerization, intraepithelial or glandular neoplasia, neoplastic foci or in situ carcinomawere not considered as cancer (and thus not included in the registration) unless there was a clear infiltration of the neoplastic tissue through the muscularis mucosae.
Tumours were classified with the tumour node metastasis (TNM) system, which closely corresponds with the Dukes classification, into four main categories [24]. This procedure follows simple physiopathological considerations and eliminatesat least in partambiguities and confusion consequent to the numerous revisions of the Dukes staging system. Thus, stage I (Dukes A) defines a neoplasm confined within the muscular wall of the large bowel; this category can be subdivided into T1N0M0, when tumours spread through the muscular mucosae into the submucosa, and T2N0M0, when tumours have infiltrated the muscular wall. In stage II (Dukes B), the tumour spreads beyond the smooth muscle (T3N0M0), or may infiltrate perirectal or pericolic organs (T4N0M0). In stage III (Dukes C), there is the metastatic involvement of lymph nodes (C-1, T14N1M0, if the involved nodes are up to three; C-2, T14N2M0 when they are four or more), independently from the dimensions and the degree of infiltration of the primary tumour. In stage IV (T14N02M1, corresponding to the D category of other classifications), the tumour metastasises to the liver, lung or, more rarely, other organs.
For the purpose of the present study, right or proximal colon was considered that part of the large bowel extending from the caecum (including the appendix) to the splenic flexure (included). Left or distal colon included the descending and sigmoid colon; rectal lesions were those located in the rectal ampulla, rectosigmoid junction and anus.
Statistical analysis
Crude, age-standardised (age-adjusted) incidence rates and cumulative risks were calculated following the general guidelines of the International Agency for Research on Cancer (IARC) [25], using the resident population at census 1991 as the denominator, and the age structure of the World population.
Poisson regression model (STATA 7 software package, Texas, USA) was used to evaluate the trends of incidence throughout the registration period. Statistical analysis was carried out by estimating a general model of regression in which sex, age at diagnosis and triennium of incidence were chosen as covariates. The trends of stage at diagnosis (TNM I versus II, III, IV or Nx) and of tumour location (right colon versus left colon or rectum) were estimated with a model of regression for every classification of stage and site using as in the previous general model sex, age at diagnosis and triennium of registration as covariate factors. Age at diagnosis was codified in to five classes: 049, 5059, 6069, 7079 and 80+ years. As reference categories, the model considered male sex, younger age at diagnosis (49 years), first triennium of registration (198486) and Dukes A tumours.
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Results |
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Discussion |
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Various studiesespecially from North Americahave suggested that colorectal malignancies have undergone a rightward shift during the last three to four decades, with right-sided lesions becoming more and left-sided less prevalent [810, 26]. However, at variance with these reports, other investigators were unable to show a definite increase of right-sided tumours. Thus, in a study of 60 000 autopsies carried out between 1928 and 1972, Parkash [27] showed a gradual increase in the incidence of colorectal carcinomas, but this occurred throughout the large bowel, with no preferential location of the lesions in the right colon. Even in North America, Lanier et al. [12] found no increase in the incidence of right-sided neoplasms, while Vobecky et al. [13] showed a relatively stable rate of proximal lesions from 1967 to 1980. Finally, in more recent years, Crerand et al. [14] evaluated the distribution of colorectal carcinomas in a large series (n = 1553) of Irish patients over a 30-year period. Their results showed that the distribution among the various anatomical subsites changed very little during the study period.
The reasons for these conflicting results remain unclear, although they could also be attributed to different criteria adopted for the division of the colorectum into anatomical subsites [16]. Thus, in some studies the right colon included only the caecum, ascending colon and hepatic flexure [10], while other authors suggested that the proximal colon should be made up of the caecum through the descending colon [16]. The criteria that we and others [14] have adopted were to consider the right colon as the portion of large bowel including caecum, ascending colon, transverse colon and flexures (and left colon the portion including descending and sigmoid colon), as suggested by either epidemiological [28] or anatomical considerations.
Other possible explanations for the different distribution of colorectal malignancies into right and left colonic segments might include (i) the impact of environmental risk factors, such as diet and lifestyle [29]; (ii) a different frequency of hereditary colorectal neoplasms (which are characterised by an increased frequency of right-sided lesions) [30]; and (iii) a more or less extensive use of colonoscopy [31]. Despite the controversies, the issue of a possible increase over time of right-sided lesions remains of fundamental relevance, since it can be viewed as one of the main points in favour of colonoscopy as the technique of choice for exploring the large bowel in screening procedures [19].
The results of the present study show that incidence rates of colonic tumours are progressively rising, while the frequency of rectal lesions have tended to decline. This trend was associated with a sharp increase of localised lesions and with a significant improvement of 5-year survival (data not shown) [32]. However, the absolute numbers of advanced (stage IV and unstaged) lesions did not show any consistent decline throughout the observation period. Similar results have been reported by several other investigators [3335]. Colonoscopy is requested more and more frequently than in the past; considering that symptoms due to colorectal lesions are often scanty, we might expect an increased detection of tumours only as a consequence of a more extensive use of endoscopy. Since women are more reluctant to undergo endoscopic examinations [36], this might particularly explain the lower incidence of cancer in females observed in this study.
Western populations continue to become older; since colorectal cancer shows a peak of incidence at ages 6570, the gradual ageing of the population probably represents the main natural factor predisposing to colorectal neoplasms. Thus, the significantly higher occurrence of colorectal cancer in the age groups 5059, 6069, 7079 and 80+ (versus individuals in whom tumours occurred before the age of 50 years) is not surprising. Finally, there is no doubt that life has become more comfortable in all western countries; this has resulted in an increase in the availability of hypercaloric food and alcoholic beverages, and a greater amount of time spent in sedentary activity (for many individuals it is not unusual nowadays to spend 1014 h watching a monitor, either computer or television). All of these factors (i.e. high intake of meat, animal fat and refined food, low intake of fibre and a tendency for low physical activity) have been associated with an increased risk of colonic tumours and, to a lesser extent, rectal neoplasms [29, 37, 38].
The more favourable staging at diagnosis (Tables 3 and 4) is presumably related to the wider use of colonoscopy, and this, in turn, can be attributed to an increased attention of patients and doctors towards the screening, early detection and symptoms of this common disease [32, 39]. However, the absolute numbers of advanced and unstaged lesions showed very little change during the registration period. This observation suggests that the more frequent use of endoscopy and the increased attention towards prevention and early diagnosis are not sufficient to induce a definite reduction in the rates of inoperable lesions and to reduce the absolute number of deaths [39]. Perhaps a vigorous promotion of lower endoscopy in the elderly population and large-scale research studies evaluating fecal occult blood testing might reveal valuable tools that may help to reduce the number of patients who present with advanced disease.
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Acknowledgements |
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FOOTNOTES |
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