Gastrointestinal cancers in Europe

Cancer involving the digestive (gastrointestinal) tract is the most common cancer in Europe (Figure 1). The most common site of gastrointestinal (GI) cancer is within the colon and rectum. Overall, colorectal cancer represents over half the cancers affecting the GI tract, with gastric cancer being the second most common, found in 23%. The data on the incidence of cancers affecting the liver are suspect. Not all liver tumours are registered because the majority of liver cancers (95%) are metastatic cancers, that is, secondaries from other sites. These metastatic cancers primarily arise from the colon and rectum, lung, breast, pancreas, stomach, oesophagus and the kidney. Over half of all liver metastases arise from a primary growth in the GI tract. Thus, the GI tract is a very common source of cancer overall. The relative distribution of these cancers is shown in Figure 2, and the distribution of cancers reported within Europe is shown in Figure 3. These indicate that the GI tract is the most common cancer site. Colorectal cancer is now numerically the most common cancer in Europe, exceeding the number of people developing lung or breast cancer. Total new cases of cancers per annum throughout Europe (showing gastrointestinal as one group) excluding skin (Source Globocan 2000). Proportion of total number of cancers of the intestinal tract throughout Europe (Source Globocan 2000). Proportion of cancers arising from the gastrointestinal tract compared with other sources of malignancy (excluding skin); new cases per annum (Source Globocan 2000). The 5-year survival rates for GI cancers reported from 16 European countries are depicted in Table 1. It can be seen that liver-related malignancy carries the worst prognosis, followed by pancreatic cancer and oesophageal cancer. There are regional differences, although survival in pancreatic cancer is uniformly poor, with 5-year survival rates of 1–9%. With the exception of Iceland, the 5-year survival figures for oesophageal cancer are also extremely poor, being 3–15%. In gastric cancer, the results in terms of 5-year survival are more variable, with Poland having only an 11% survival and the UK only a 12% survival, whereas figures from Spain and Austria (28%) are very much better. It can be seen that the prognosis in colorectal cancer is far more promising than all other intestinal cancer sites. Poor survival rates for intestinal cancer are found in communities with low socio-economic circumstances, reflecting poor general nutritional status and the tendency to present later to healthcare providers. Cancers affecting the upper two-thirds of the gullet are usually squamous cell tumours. These tend to respond well to radiotherapy and may carry a better prognosis. The second common type of gullet cancer is adenocarcinoma, which arises from columnar epithelium. Adenocarcinomas tend to be much more common in the lower part of the oesophagus. They behave in a similar manner to gastric cancer, have a worse prognosis and do not respond to radiotherapy. Over the past 3 decades, there has been a gradual increase in the proportion of adenocarcinomas of the oesophagus. This is thought to reflect the increasing prevalence of gastro-oesophageal reflux disease. Oesophageal cancer represents 5.9% of intestinal malignant disease. The number of new cancers per year in Europe is 34 332. A high proportion of oesophageal cancers compared with other intestinal malignancies were identified in France (10%), Ireland (10%), Iceland (10%) and the UK (10.9%). The overall crude comparative percentage 5-year survival figures for oesophageal cancer are shown in Figure 4. Five-year survival figures are reported as only 3% in Poland, Slovenia and Estonia, which compares badly with the best figures reported (Austria, 14%; Sweden, 14%; Netherlands, 12%). Overall comparative percentage 5-year survival figures for oesophageal cancer. If we look at the actual number of new diagnoses per year compared with the number of deaths per year (Table 2), it can be seen that the prognosis for oesophageal cancer is dismal, with mortality figures occasionally exceeding the number of new cases per year. Oesophageal cancer tends to occur in the elderly, with a maximum distribution between the age of 60 and 80 years. Males exceed females by a ratio of 3 : 1. There are no readily identifiable premalignant lesions that might be used to detect patients at risk of developing oesophageal cancer, except for patients with Barrett's oesophagus complicating long-standing gastro-oesophageal reflux. There might therefore be some prospect of identifying high-risk individuals by offering endoscopy to those patients with a long history of reflux symptoms in order to detect the presence of a columnar-lined oesophagus, which is associated with a higher risk of malignancy. Additional risk factors include obesity and smoking. The risk of squamous cell cancer is increased in smokers, in association with leukoplakia and achalasia (a motility disorder due to spasm of the lower oesophagus), and by certain foods. Foods that are known to increase the risk of oesophageal cancer include salted fish and pickled vegetables, as does tobacco and betel-nut chewing. Oesophageal cancer from chewing betel-nut is now becoming more prevalent because of a higher proportion of Asian citizens residing within Europe. The classical presentation of cancer affecting the gullet is progressive difficulty with swallowing. The average duration of symptoms prior to diagnosis ranges between 3 and 9 months. Late clinical features include chest pain and weight loss. Diagnosis is made by endoscopy and biopsy. Staging of the local spread of the tumour, particularly if it is not obstructing the gullet, can be assessed extremely accurately by endoscopic ultrasound. Unfortunately, by the time an oesophageal tumour causes difficulty with swallowing, the tumour has usually spread outside the wall of the gullet into surrounding structures, particularly the great blood vessels of the chest, the lymph nodes in the mediastinum, and sometimes into the air passages also. Thus, staging oesophageal cancer is crucially important in deciding whether a tumour is operable or not. Several endoscopic and radiological techniques are usually combined to determine resectability. Treatment of oesophageal cancer is by surgical resection. Unfortunately, only 25–30% of all oesophageal cancers are operable. Surgery is extensive, and resections for potential cure inevitably require a bed in the intensive treatment unit, with a mean stay of 1–5 days. The average hospital stay following oesophageal cancer resection is 12–30 days. There is a 5–10% operative mortality. There is a risk of leakage from the bowel reconstruction of 5–10%, which carries a 30% mortality. Of tumours that are operable, approximately 25%, the overall 5-year survival is 20–30%. Patients who first present with advanced disease where surgical resection is impossible receive palliative treatment. Such patients have a life expectancy of between 4 and 12 months. Conventional palliative surgical resection or bypass places an enormous strain on healthcare budgets. Consequently, there is renewed interest in alternative endoscopic palliative techniques and in chemo- or radio-therapy where appropriate. The principal cause of expenditure in the treatment of oesophageal cancer is hospital admission and operative treatment, inevitably involving an intensive care bed and a prolonged hospital stay, particularly if there are any complications of the surgical treatment. Radiotherapy may be used to palliate but chemotherapy is not aggressively used. Most of the additional expenditure is on palliative care. Improved survival for oesophageal cancer might be achieved by screening high-risk individuals with potential Barrett's oesophagus. Thus, there would be some merit in offering endoscopic surveillance in patients over 50 years of age with a long history of heartburn. These patients should have biopsies of the lower oesophagus to exclude dysplasia. If high-grade dysplasia is seen on more than one occasion, there may be some merit in prophylactic surgery. At the other end of the spectrum, increased palliation to avoid the morbidity of major surgery using endoscopic stenting should be encouraged. Adenocarcinomas make up 90% of gastric tumours, with the remainder being lymphomas (7%) and leiomyomas (3%). The overall incidence of gastric cancer in Europe is high and represents 22.6% of all GI cancers. The number of new cancers in Europe in 2000 was 130 810. Gastric cancer principally affects the elderly. Eighty per cent of tumours are diagnosed between the ages of 60 and 80 years. There has been a falling incidence of gastric cancer over the past decade. Furthermore, the distribution of gastric cancer has changed over the past 3 decades; whereas antral cancers used to dominate, now there is almost an equal incidence of antral and proximal cancers (near the gastro-oesophageal junction). The reasons underlying this change are as yet unclear, although the falling prevalence of H. pylori, coupled with the increasing incidence of reflux disease may play key roles. Males are affected twice as often as females. Gastric cancer is among those tumours associated with the worst survival. Some countries have an abnormally high proportion of gastric cancers, including Belarus (47%), Ukraine (39%), Lithuania (37%), Latvia (34%), Estonia (34%), Portugal (33%), Romania (32%) and Bulgaria (31%). The prognosis of gastric cancer remains poor. Countries with a poor 5-year survival figure include Poland (11%), UK (12%), Denmark (14%) and Sweden (17%). By contrast, countries reporting more favourable 5-year survival figures include Austria (28%), Spain (28%), Germany (27%) and France (25%) (Figure 5). The poor prognosis of gastric cancer is highlighted in Table 3, where the number of deaths per year is only 20% less than the number of new cases registered per year in Europe. Overall comparative percentage 5-year survival figures for gastric cancer. Risk factors for gastric cancer include environmental factors such as malnutrition and poor socio-economic circumstances. Other factors associated with an increased risk of gastric cancer include smoking and certain food products. There is a well-recognized correlation between nitrites, nitrates and nitrosamines, which may be used in food preservatives that are potentially carcinogenic. There is now good evidence that long-standing colonization of the stomach by Helicobacter pylori increases the risk of gastric neoplasia. Other conditions associated with an increased risk of gastric cancer include gastric polyps, gastric ulcers and atrophic gastritis. Unstable gastric epithelium (the lining of the stomach) may be associated with an increased risk of gastric cancer. Conditions associated with unstable epithelium are called intestinal metaplasia or dysplasia. In Japan, because of the high risk of gastric cancer associated with their diet, there has been a national endoscopic surveillance programme within the commercial workforce. Small irregularities of the inner lining of the stomach wall could be identified and were sometimes early forms of gastric cancer. When these patients, whose disease is confined to the inner lining of the stomach wall, were offered gastric resections, lymph node invasion from the tumour was uncommon and the 5-year survival was of the order of 95%. For some years, clinicians were under the impression that early gastric cancer was a Japanese disease. Surveillance programmes in Europe have demonstrated that this is not the case. However, in Europe as opposed to Japan, the relative incidence of gastric cancer is not particularly high and thus the justification for endoscopic surveillance of asymptomatic patients never became a high national imperative. Nevertheless, careful endoscopy in patients with indigestion does from time to time identify small mucosal lesions with biopsy evidence of adenocarcinoma where gastric resection is associated with a comparable 5-year survival rate of 95%. Most gastric cancers in Europe (90%), are symptomatic and are advanced gastric cancers. Most of these patients present with symptoms of indigestion, which is often vague, where urgent investigation may not seem necessary. As the gastric tumours enlarge, so patients develop symptoms of weight loss, anaemia, difficulty swallowing, vomiting, abdominal pain and abdominal fullness. Gastric cancer initially spreads through the wall of the stomach but quickly involves regional lymph glands. It is diagnosed by endoscopic examination and by biopsy. Staging gastric cancer is best achieved using computed tomography scanning and occasionally by laparoscopy and laparoscopic ultrasound. Gastric adenocarcinoma is usually treated by surgical resection. Unfortunately, only 55–65% of gastric cancers are resectable when first diagnosed. Surgical resection for cure is only achieved in about 40% of cases. Operations carry a 5% mortality and approximately 10% of patients develop complications. Intensive treatment unit beds are needed for approximately 30% of patients with gastric cancer and the average hospital stay ranges from 10 to 24 days. The 5-year survival is closely related to the spread of the tumour, and varies from 95% for early cancers to only 20% for extensive lesions. There is no evidence that radiotherapy or chemotherapy substantially improves survival. Thus, where possible, conventional surgical resection should be confined to patients with operable tumours in whom the prognosis would appear to be favourable. Unlike oesophageal cancer, there is no simple method of palliating gastric adenocarcinoma, which frequently presents with vomiting and obstruction of the stomach, and sometimes obstruction to the biliary passages also. Thus, palliative bypass operations are still frequently required even though the 1-year survival is only 10–20%. The principal costs of treating gastric adenocarcinoma are in-patient hospital expenditure for investigations and surgical resection. The cost for in-patient treatment is less than for oesophageal cancer because hospital stay is shorter and the use of an intensive treatment unit is less. Other areas of expenditure include chemotherapy, outpatient visits, and palliative care. Pancreatic cancer may arise from the duct tissue or from the glandular tissue. It may affect the body of the pancreas gland or the ampulla at the confluence of the distal common bile duct and pancreatic duct. Peri-ampullary cancers may arise from the wall of the duodenum, from the ampulla itself or from the distal bile duct. In addition to pancreatic cancer, there may be separate cancers of the bile duct itself or of the gallbladder. These will be considered separately. Carcinoma of the bile duct is relatively rare. It is more common in patients with pre-existing sclerosing cholangitis that may be a complication of inflammatory bowel disease. Most patients with bile duct carcinoma present with jaundice, weight loss and abdominal pain. Diagnosis is by endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance imaging or computed tomography scan. Most bile duct cancers have a poor prognosis and the resectability is less than 10%. Two-year survival is less than 10% and there is no response to chemotherapy or radiotherapy. Stenting of the bile duct obstruction often provides good palliation and overcomes obstructive jaundice. Carcinoma of the gallbladder is rare. Women are four times more likely to develop gallbladder cancer than men, and 90% of gallbladder carcinomas are adenocarcinomas. Gallbladder carcinoma is almost invariably associated with long-standing gallstones, and in fact, gallbladder cancer can be an incidental finding during the removal of the gallbladder for stones. In these cases, the prognosis is usually excellent, with a 5-year survival rate of 70%. If, on the other hand, a gallbladder cancer presents with symptoms of abdominal pain, weight loss and jaundice, the 1-year survival is less than 10%, and a high proportion of tumours are irresectable. Peri-ampullary carcinoma describes tumours that are located around the distal end of the bile duct and pancreatic duct. The tumour may arise in the duodenal mucosa adjacent to the ampulla, from the lining of the distal bile duct, or from the ampulla itself. These peri-ampullary tumours tend to have a very favourable prognosis because they present early with jaundice, but they represent only 7% of pancreatic cancers. Carcinoma of the body of the pancreas arises either from the ductal tissue or from the glandular tissue within the body of the pancreas. These tumours have a much less favourable prognosis because they present late with pain and weight loss. Only later in the natural history of the cancer do they present with jaundice. These tumours represent 93% of pancreatic cancers. Pancreatic tumours represent 10.4% of all intestinal malignancies in Europe, and 60 139 new cases were diagnosed in 2000. Countries having an abnormally high proportion of pancreatic cancer compared with other GI sites include Lithuania (14%), Greece, the Czech Republic, Poland, Switzerland and Cyprus (13%). There is some epidemiological evidence within Europe to suggest that the incidence of carcinoma of the pancreas is increasing. It occurs more commonly in men than women. It principally affects the elderly; 50–70 years of age. The prognosis of pancreatic cancer is extremely dismal and is one of the worst of all malignancies. Over 90% of patients with pancreatic cancer are dead within 1 year of referral and diagnosis. The 5-year survival figures for pancreatic cancer are reasonably uniform throughout Europe, ranging from 1 to 9%. Countries with a poor 5-year survival include Estonia (1%), Switzerland, Netherlands and Denmark (2%). The best 5-year survival figures come from Austria (9%) and France (8%), but even these are very poor (Figure 6). The annual incidence and death rates for pancreatic cancer are given in Table 4, where it can be seen that the number of deaths per year exceed the number of new cases, indicating its appalling prognosis. Overall comparative percentage 5-year survival figures for pancreatic cancer. Peri-ampullary carcinoma tends to have a favourable prognosis because it presents early with obstructive jaundice. Usually this is painless. The diagnosis can be easily made at ERCP. Sometimes peri-ampullary carcinoma may be treated by local excision, particularly if the tumour arises from the duodenum. Radical resection, however, usually involves pancreatico-duodenectomy (Whipple's operation), removing the outlet of the stomach, the pancreas, the duodenum and the lower end of the bile duct. This is an extensive operation. Nevertheless, for early favourable cancer the results are good, with an operative mortality of 3–5%, a resectability rate of 70% and a 20–40% survival rate at 5 years. Unfortunately, most patients with carcinoma of the body of the pancreas present late with vague symptoms of nausea, weight loss, abdominal pain and jaundice. Unlike peri-ampullary carcinoma, diagnosis is much more difficult. Sometimes carcinoma of the pancreas can be demonstrated on ERCP, usually however, it is necessary to rely on cross-sectional imaging with computed tomography or magnetic resonance imaging. Carcinoma of the body of the pancreas tends to spread to local surrounding structures that make it inoperable. The tumour may spread into the major vessels of the abdominal cavity or into the posterior abdominal wall; lymphatic spread is generally widespread. Conventional treatment of pancreatic cancer is extremely disappointing. Only 10% of tumours are resectable. Radical resection is required for cure. Patients require intensive treatment unit care for such radical resections and the average hospital stay is 14–32 days. The operative mortality is between 5 and 8%. The incidence of complications after major surgical resection is 15% and the overall 5-year survival is 10–15%. Radiotherapy and chemotherapy are rarely beneficial for treatment. Because the prognosis is so dismal, and as the prospects of cure from a major surgical operation are poor, there is increasing interest in palliation by endoscopic stenting. The principal costs of managing pancreatic cancer are inpatient hospital treatment. These involve highly expensive surgical resection, the inevitable use of intensive treatment unit facilities, a long hospital stay, and high-density medical and nursing manpower. Costs of outpatient surveillance and additional treatment are small. Apart from inpatient hospital costs, the other principal expenditure is in palliative care. Small-bowel cancers represent less than 2% of all gastrointestinal neoplasms. There are three major forms of small-bowel tumour. They include adenocarcinoma, lymphoma and carcinoid tumours. Diagnosis is made by examination or computed tomography scan. Adenocarcinomas principally involve the upper small the duodenum and the They may be found in patients with and colorectal cancer forms of colon cancer. Small-bowel adenocarcinomas usually present with obstruction and are treated by resection. If diagnosed early the prognosis may be reasonably are the most common of small-bowel tumour. There are a of The prognosis is Most lymphomas are treated by resection and tumours are found in the small bowel or The small is one of the more common sites of carcinoid tumour. They tend to and early to regional lymph and the metastases are often associated with a of and due to of high of in the Conditions that may to adenocarcinoma include small-bowel polyps, and Small-bowel cancer may small-bowel disease. There is an increased risk of lymphoma in patients with disease. Most (95%) of tumours involving the liver are from adenocarcinoma or squamous cell carcinoma the dismal 5-year survival figures for liver cancer (Figure Overall comparative percentage 5-year survival figures for liver cancer. cancer of the liver is relatively rare. There are three carcinoma, which may or which arises from the of the liver and is and a of other tumours, of which are such as The principal to carcinoma is of the usually from or other Patients who have from and not only have an increased risk of but also of is now becoming a in Europe, with a high prevalence rate of among the asymptomatic in countries and in Europe. Consequently, there has been an increasing incidence of carcinoma within Europe and the incidence of this of cancer is to as a of the of Unfortunately, carcinoma tends to present late with an abdominal weight loss, pain and jaundice. In patients with known there is often a in liver Diagnosis of carcinoma may be particularly in the tomography or may be of is only if this is a in a relatively Such a is Most are enormous and there is Consequently, liver may be although there is a high risk of particularly in the The results of chemotherapy are disappointing. The overall 5-year survival rate is less than 10%. If carcinoma the cost of radical surgical treatment is because is the only of a cure. For most patients, however, costs are related to palliative care because surgical treatment is not Most liver tumours (95%) are cancer sites in order of and Most patients with metastatic carcinoma in the liver present late with pain, and weight loss. Diagnosis is often made by computed tomography scan. For most cases of metastatic liver cancer, treatment is There is a small for palliation with or or by The principal cost for managing metastatic liver cancer is palliative treatment. Colorectal adenocarcinoma is now the most common malignant tumour in Europe. all of these bowel cancers are Other tumours affecting the include squamous cell carcinoma, carcinoid tumours, malignant and of the colon and are the most common cancers in Europe. They represent over half of all intestinal in Europe, which represents new cases a year. Countries with an abnormally high proportion of colorectal cancers include Denmark Netherlands Sweden Germany and Ireland The number of new cases and deaths from colon and cancer per year per individuals on the for and females is shown in Table Countries with the incidence are the Czech Republic, and Germany (Figure When compared with the of the these high-risk countries represent an incidence that is almost that of the particularly in In the European exceed whereas in the the number of new cases per year per is for and for females. By contrast, in the number of new cases per year per individuals is for and for females. Of even interest are European countries with a low incidence of colorectal cancer. The low rates are found in Greece, and Thus, there is an enormous in the incidence throughout Europe, where rates may be times higher in certain countries than (Figure It can be seen from Table 5 that the number of new cases is almost twice as high as the number of deaths per indicating a more favourable prognosis. and mortality rates for and females are shown in Table of colorectal cancer incidence in Europe for on and females on number of new cancer cases per individuals in of colorectal new cases per year per The mortality rates for colorectal cancer from to The mortality for colorectal cancer per for and females is depicted in Figure and the overall percentage of 5-year survival for all colorectal cancers, of for colon and rectum, is in Figure Countries with a poor 5-year survival for colorectal cancer include Poland Slovenia Estonia and (39%), UK and Denmark (Figure Countries associated with a more favourable 5-year survival rate include the Netherlands Iceland Sweden and France There are regional in incidence in men and with a high in and Europe, the and (Figure for colorectal deaths per year per 5-year survival of all colorectal cancer for colon and rectum. Overall comparative percentage 5-year survival figures for colorectal cancer. mortality from colorectal cancer The data are for in Europe, mortality rates per are depicted to being less than per being more than per There is some evidence that the mortality from colorectal cancer in Europe is now in contrast, the overall incidence is increasing. rates are on the increase in countries (Figure falling or the in countries (Figure and are in countries (Figure rates per annum per in countries with a high incidence of colorectal on females on rates per annum per in countries with an incidence of colorectal on females on rates per annum per in countries with a low incidence of colorectal on females on The risk of adenocarcinoma of the colon in the as a is approximately Males are more likely to be affected by and cancer than but the is not very may be found between and years of the principal age for of colorectal cancer is between 50 and 80 years. Of patients with adenocarcinoma of