Audit of advanced gastric cancer at Ibn Sina Hospital , Khartoum , Sudan

Background: Worldwide, gastric cancer is the second most common cancer (second to lung cancer). In Sudan incidence and prevalence are not clear because of absence of National Cancer Registry. Purpose: To find out the frequency of the gastric mesenchymal tumours and whether gender and age influences the clinicopathological features of gastric cancer and to audit the outcome of management of advanced gastric cancer at Ibn Sina Hospital. Methods: This is a retrospective study in 139 gastric cancer patients admitted from May 1997 through November 2004. Demographic data and details of the clinical and endoscopic features of gastric cancer, as well as the operative details, and histopathology, the post-operative complication hospital mortality were analysed Available data on family history of cancer; smoking and alcohol consumption was also collected.

There is no perfect National Cancer Registry in Sudan.Hence, there is no crystal clear explanation why we are seeing an increasing number of cancer patients and in particular gastric cancer.Environmental factors, dietary change, increased awareness and improvement in roads might have increased the influx of cancer patients.Radioactive material buried or originally present in the soil with spread of this radiation through the deep waters or by direct pollution of the environment, and canned food aid, during the long years of drought and civil war, potassium bromide, dioxin, and some organophosphorous compounds used in agriculture as fertilizers, insecticides and pesticides may have increased the magnitude of cancer.Extensive epidemiological studies are urgently needed to find out the effect of high salt consumption in salted fish (Fasikh and Malouha, and Kagiek) and starchy (rice), pickled, and smoked foods (Probably Salat and Shia); and low caloric, low fresh fruits and fresh vegetables intake, drinking of contaminated water and pollution of water by tar on the surface of the skin containers in villages (Girba).Environmental factors are of greater importance in triggering the disease in patients with genetic predisposition.Unfortunately almost all gastric cancer patients referred to Ibn Sina Hospital have advanced disease.This is either due to the late presentation of patients to the medical facilities available, and/or in part some delay may occur when gastric ulcers are treated as if it is only a benign condition.However, patients seem to be forced to come to the surgeons when the manifestations of late cancer as anaemia, loss of weight, recurrent vomiting and pain exist.

Purpose:
To find out the frequency of the gastric mesenchymal tumours in patients seen at the specialized gastrointestinal unit based at Ibn Sina Hospital.Also to see gender and age influences on clinico-pathological features of gastric carcinoma as a base line for future immunohistochemical and genetic studies in Sudanese patients with gastric cancer in.To audit the outcome of management of advanced gastric cancer.Patients and methods: Definition: The advanced gastric carcinoma is defined as gastric tumours that invade the muscularis propria and/or associated with metastases to regional lymph nodes or invade adjacent or distant structure.Hospital mortality is defined as death within 30 days after surgery.

Methods:
Retrospective study of 139 patients admitted to the surgical unitas at Ibn Sina Hospital with a diagnosis of carcinoma of the stomach from May 1997 through November 2004.

Selection criteria:
Files of all patients admitted to the surgical unit at Ibn Sina Hospital with the diagnosis of gastric cancer which fulfilled the criteria for the definition of advanced gastric cancer stated above were included in this study.Demographic data as well as the clinical features such as epigastric pain, vomiting, loss of weight and all information obtained by clinical examination as pallor, cachexia, epigastric mass, enlarged left supraclavicular lymph node and by investigations like the haemoglobin concentration, endoscopic features, site of gastric cancer, and the operative findings such as site ,size of the tumour, enlarged lymph nodes, fixity of the tumour, its invasion to adjacent structures, liver metastasis and peritoneal seedlings were retrieved from the files.Details of histology reports involvement of lymph nodes were also collected.Types of gastric resection was noted and complications as well as hospital mortality in one month was registered.Available data on family history of cancer, smoking snuff and alcohol consumption was also collected.The patients were then categorised into three limbs according to their age <40, 40-60 and > 60 years.The disease characteristics was worked up in each age group in an attempt to find out if there is specific clinicopathological pattern of gastric cancer related to age or sex.

Statistical analysis:
The data was fed into a Statistical Package of Social Sciences (SPSS 11.5 Chicago-Illinois).Analysis was done using cross tabulation, 2 where appropriate considering the significant level at P = 0.05.

Dysphagia:
23 (16.5%) of the study population suffer from dysphagia.The frequency of dysphagia seems to be in a direct proportion with advancing age i.e. carcinoma of the cardia increases with age with 14 out of 23 patients in the age group >60 years ( 2 8.926 P 0.012).Also, dysphagia seems to be higher in males compared to females i.e. 16(69.6%)males compared to 7(30.4%) females due to the sex composition of the cohort.

Pain:
Epigastric pain is a predominant feature of advanced gastric cancer in all age groups ( 2 9.515 P 0.009).Like dysphagia the number of male patients that admit to have epigastric pain 85(66.9%) is double that of 42(33.1%)females who complain of pain.Yet, this difference in gender has no significant statistical difference (P 0.985).

Vomiting:
Like pain, a large number of patients with advanced gastric cancer suffer from vomiting but there is no statistical significant difference in the frequency of vomiting in both males and females ( 2 1.104 P 0.465) likewise there in is no significant statistical difference in frequency of vomiting in the different age categories ( 2 1.531 P0.12)

Weight loss:
81(67.5%) male and 39(32.5)females complained of loss of weight.However, there is no significant impact of gender on weight loss ( 2 140 P 0.709)

Haemoglobin concentration:
In this study anaemia is found to be very common in advanced gastric cancer in all age groups.Haemoglobin is categorized into 2 categories namely below 10 gm/dl versus equal to or more than 10 gm/dl.Just more than half the patients in each age category suffer from haemoglobin level below 10gm/dl.88 (63.3%) have Hb less than 10gm/dl.33(37.5%)females out of the 88 patients who presented with Hb less than 10gm/dl but these 33females comprise 71.7% of the total female population and the 55 males comprising 59.1% of the total male population in the study.

Site of gastric tumour:
The commonest site of carcinoma of the stomach is the antrum 55 (39.6%) followed by the cardia 34(24.5%)followed by carcinoma of the cardia which seems to increase with age ( 2 20.280 P 0.208).Comparable pattern of distribution is also found in both males and females with no significant statistical difference ( 2 5.413 P 0.713) The naked eye appearance: Endoscopic reports and operative findings showed that the ulcerative type of gastric cancer is the commonest type followed by the fungating tumours.When the naked eye appearance of advanced gastric cancer is plotted against age the ulcerative type is the most frequently seen type in all age groups ( 2 18.987 P 0.089) and in both sexes ( 2

Discussion
Worldwide, gastric adenocarcinoma is the second most common cancer (second to lung cancer).
The global incidence of gastric cancer differs in different geographical areas.The highest incidence i.e. >30 cases per 100,000 population is in Japan, Russia, China, South America, and Eastern Europe.The lowest incidence i.e. <3.7 cases per 100,000 population is in North America, Western Europe, Australia, and New Zealand 7, 8, 9, 10,.A marked reduction has been observed in the incidence of gastric carcinoma in North America and Western Europe in the last 50 years.However, the 5-year survival rates are less than 20%, as most patients who present late and are unsuitable for curative, radical surgery 9, 10, .In comparison because there is no National Cancer Registry In Sudan yet, there is no accurate incidence or prevalence of any sort of cancer in Sudan.Therefore, there is no crystal clear explanation for the increasing number of cancer patients and in particular gastric cancer that we are seeing in our surgical practice.Till a National Cancer Registry is formulated we will continue to depend on hospital based data; expected to have a high load of gastrointestinal cancer.In this study, there is statistically significant male predominance (P 0.04).The male predominance in this study is consistent with the fact that gastric cancer is more common in males as reported in literature 11, 12, 13, 14.However, in this study the prevalence of gastric cancer is equally distributed between males and females below the age of 40 as shown in Fig 2 .The reason for this equity is not clear and the reason why after the age of 40 males are more prone to develop carcinoma of the stomach than females needs further investigations.However, Su-Shun LO et al 11 reported significantly higher percentage of females among patients less than 39 years of age.The peak frequency of gastric cancer was at the age group 50-65 years comprising 64(46%) of the total population in the study.However 29 (20.9%)patients were under the age of 40 years.In this study we found that the male to female ratio in patients less than 39 years of age to be 1:1.1 which is very much comparable to the finding of Shun LO et al 11 However, Shun LO et al 11 reported that the percentage of patients equal 39 years or younger is 3.7% which is very much less than that in the same age group in our patients which is 20.9%.The high prevalence of gastric cancer among patients younger than 39 years of age in our study needs explanation by further studies to find out the impact of environmental and genetic factors on the prevalence of gastric cancer in this relatively young age group in the Sudan.
Epigastric pain, which is a feature of advanced gastric cancer, is proved in this study to be a predominant feature in all age groups; however, it is significantly less in patients older than 60 years of age (P 0.009).This may be explained by the fact that older people are probably more tolerant than young people.On the other hand, gender has no specific effect on frequency of pain (P 0.985).
23 (16.5%) of the study population suffer from dysphagia.The frequency of dysphagia seems to be in a direct proportion with advancing age (P0.012).However, dysphagia seems to have no predilection for any particular sex because there is no significant statistical difference in frequency of dysphagia in both sexes (P 0.769).
In this study a large number of patients with advanced gastric cancer suffer from vomiting.There is no statistically significant difference in the frequency of vomiting in the different age categories ( 2 1.531 P 0.465) and in males and females ( 2 1.104 P 0.293).This could be explained by the fact that the ulcerative type of gastric cancer is the commonest type encountered in our study comprising 62(44.6%).Advanced gastric cancer invades the gastric mucosa, ulcerates and leads to unnoticeable blood loss in the lumen of the gastrointestinal tract.In this study anaemia is found to be very Although the gastric antrum is the commonest site affected by cancer at all age groups, the frequency of affliction of the gastric antrum cancer has no statistically significant difference over involvement of other sites of the stomach in all age categories (P 0.208) nor in males and females (P 0.713).The intestinal type of gastric cancer, with well-formed glandular structures is more likely to involve the distal stomach and to occur in patients with atrophic gastritis.This type has a strong environmental association.The diffuse type with poorly cohesive cells tends to infiltrate the gastric wall.Tumours of this type may involve any part of the stomach, especially the cardia, and they have a worse prognosis.Unlike type 1 gastric cancers, type 2 cancers have a similar frequency in all geographic areas.Before 1950, most gastric tumours were located in the antrum.Since then, the location has gradually shifted from the antrum to the body and fundus because of the rapidly increasing incidence of carcinoma in the gastric cardia and lower oesophagus.As a consequence, 30% of the lesions are found in the antrum, 30% are in the body, and 40% are in the fundus and cardia.The declining incidence of gastric cancer in the USA and Western Europe largely reflects a decline in distal lesions.In contrast, there has been a steady rise in the incidence of adenocarcinoma of the proximal stomach and the gastroesophageal junction in the USA and Europe 16,17,18 .However, more recent data from Sweden indicate an overall decline in incidence of cancers distal to the cardia by 9% [6-12%] per year, but did not confirm a rise of cardia cancer which has remained stable 19 .Gastric carcinoma is twice more common in men than in women.Moreover, carcinoma of the cardia of the stomach is up to 7 times as common in men as in women 15.When the naked eye appearance of advanced gastric cancer is plotted against age the ulcerative type is the most frequently seen type.However, gastric cancer seems to have the same pattern of naked eye appearance in all age groups and both sexes.
Adenocarcinoma is the commonest type of gastric cancer in all age groups and in both sexes.When the histopathology results were plotted against gender in this study it showed statistically significant difference (P 0.05) which could be explained by the fact that gastric lymphoma and signet ring were found predominantly in males.However, this may need further verification by studying larger number of patients.In this study mesenchymal tumours such as lymphoma, leiomyosarcoma and carcinoids tumours constituted 15(10.9%) of all gastric cancer.Lymphoma alone comprise 5.8% while leiomyosarcoma constitute 4.4% of all gastric carcinoma, but gastric carcinoids tumour is extremely rare and was encountered in only one case of all gastric carcinoma.The frequency of mesenchymal gastric cancers as seen in this study is in keeping with the rarity of this type of cancer world wide as published in literature 1,2,3,4,5,6 .
In this study 18 out of 61 patients were previously diagnosed to be suffering benign ulcer and were given treatment for not less than 3 months.It appears that awareness of young doctors need to be raised to refer each and every case of gastric ulcer to the surgeons and to consolidate the fact that the rationale of treatment of gastric ulcer is to remove the ulcer bearing area for histopathology.
Alcohol consumption was found in 12 (8.6%)patients.All patients who had admitted to take regularly alcohol were above 40 years of age.Likewise regular cigarette smoking was found in 14(10.8%)patients all of whom were above 40 years of age and were predominantly males.Nonetheless, studying of predisposing factors for cancer needs multidisciplinary research and rather big financial budgets.
Positive family history of cancer was found in only 5(3.6%) patients.We feel strongly that good budget should be located for further environmental and immunohistochemical studies to find out the influence of genetic predisposition and the effect of salted fish Like Fasiekh, Malouha and Kagiek as well as the levels of toxic penetration of tar painted local leather water coolers in pollution of drinking water.
The hospital mortality was 18 (12.9%).There is no significant statistical difference in the hospital mortality rate in the different age and groups and gender (P 0.853 and P 0.575 respectively).Lymph node metastases occurred in approximately 80% of patients with gastric cancer.The frequency is related to the size and depth of the tumour.The local perigastric nodes are involved first, followed by the regional (celiac, hepatic, left gastric, splenic) and distant (left supraclavicular and axillary) nodes.The local nodes (N1) are located in the prepyloric region and in the gastrocolic and gastrohepatic ligaments.These nodes are removed by performing the standard gastrectomy procedure.The regional nodes (N2) are not removed by the gastrectomy procedure; thus, their detection is more important.The N2 nodes are in the porta-hepatis, hepatoduodenal ligament, and peripancreatic region.In the TNM classification, nodal staging is related to the number of regional nodes involved in the perigastric group and around the celiac axis.Enlarged nodes elsewhere (e.g. in the retroperitoneum and mesentery) are classified as distant metastases.N1 indicates 1-4 nodes; N2, 7-15 nodes; and N3, more than 15 nodes.
Several reports used the WHO-classification, while others used the histologic classification according to the Lauren.Thus, there is confusion among physicians.It is therefore useful and of practical value to see whether these two classifications systems can easily and simply be combined.Indeed, in general, well and moderately differentiated cancer of WHO correspond to intestinal type according to Lauren, whereas poor differentiated or undifferentiated or signet ring cell -carcinoma to the diffuse type carcinoma respectively.
The decline in overall incidence of gastric carcinoma during this century appears to be largely attributable to a decrease of the intestinal-type lesions, while the occurrence of diffuse type is thought to have remained more stable 20,21,22 .Most recent epidemiological data from North Europe (Sweden) however, indicate that both types decline markedly, at similar rapidity, and with no significant trend differences between the intestinal and diffuse types 23.In this study the hospital mortality is related to the late presentation of advanced disease because 14 patients died with inoperable tumours.The mortality related to surgery in advanced gastric cancer.In this study the mortality rate was zero%, 2.8%, and 3.6% in distal subtotal, proximal subtotal and total gastrectomy respectively (Fig 3).Also, the morbidity rate in this study was quite acceptable as shown in table 1.The relationship between prognosis and age distribution of patients with gastric cancer has been controversial.Many series 24,25 showed a poorer prognosis in young patients, but some series 26,27 demonstrated that the difference of prognosis between young and old patients can be attributable to the difference in tumour stages.In this study lymph node metastasis did not show any statistically significant difference (P 0.380).
In conclusion gastric carcinoma in this study was found to be more common in males.It has a similar clinicopathological pattern in all age groups and in both sexes.Mesenchymal tumours occurred in 15(10.9%) of all gastric cancer.The hospital mortality rate was zero%, 2.8%, and 3.6% in distal subtotal, proximal subtotal and total gastrectomy respectively.

Fig 1 :
Fig 1: Age distribution of patients with carcinoma of the stomach

Table 1 :
The morbidity of advanced gastric cancer * Followed by death