Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland.

BACKGROUND: Screening for colorectal cancer (CRC) with guaiac-based faecal occult-blood test (FOBT) has been reported to reduce CRC mortality in randomised trials in the 1990s, but not in routine screening, so far. In Finland, a large randomised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004. We evaluate the effectiveness of screening as a public health policy in the largest population so far reported. METHODS: We randomly allocated (1:1) men and women aged 60-69 years to those invited for screening and those not invited (controls), between 2004 and 2012. This resulted in 180 210 subjects in the screening arm and 180 282 in the control arm. In 2012, the programme covered 43% of the target age population in Finland. RESULTS: The median follow-up time was 4.5 years (maximum 8.3 years), with a total of 1.6 million person-years. The CRC incidence rate ratio between the screening and control arm was 1.11 (95% CI 1.01 to 1.23). The mortality rate ratio from CRC between the screening and control arm was 1.04 (0.84 to 1.28), respectively. The CRC mortality risk ratio was 0.88 (0.66 to 1.16) and 1.33 (0.94 to 1.87) in males and females, respectively. CONCLUSIONS: We did not find any effect in a randomised health services study of FOBT screening on CRC mortality. The substantial effect difference between males and females is inconsistent with the evidence from randomised clinical trials and with the recommendations of several international organisations. Even if our findings are still inconclusive, they highlight the importance of randomised evaluation when new health policies are implemented. TRIAL REGISTRATION: 002_2010_august.

Proliferative and anti-apoptotic activity of esophageal mucosa in gastroesophageal reflux disease is not affected by fundoplication: a 4-year follow-up study.

BACKGROUND: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. METHODS: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. RESULTS: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). CONCLUSIONS: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD.

Early detection of colorectal cancer with faecal occult blood test screening.

BACKGROUND: Faecal occult blood test (FOBT) screening has been shown to decrease the incidence and mortality from colorectal cancer. This study compared the stage profile of patients with colorectal cancer diagnosed at the first FOBT screening round with that of an unscreened control group. METHODS: Subjects aged 60-64 years were allocated randomly to biennial FOBT screening (52 998 subjects) or a control group (53 002) in a Finnish prospective public health policy in 2004-2006. FOBT was performed with a guaiac test. At the end of 2007 the screened and control populations were linked to the Finnish Cancer Registry database, and the colonoscopic findings in the screen positives were analysed. RESULTS: Early-stage colorectal cancer was observed in 52 per cent of the FOBT-positive subjects, in 42.2 per cent of the total screened population and in 38 per cent of the control population (P = 0.191 for FOBT positives, P = 0.592 for total screened population). The prevalence of adenomas and colorectal cancer was 31.5 and 8.2 per cent respectively among the 806 subjects with a positive FOBT. Some 27.3 per cent of all colorectal tumours in the screened population were interval cancers. The tumour was located in the right colon in 28.9 per cent of the screened subjects and 22 per cent of controls (P = 0.255). CONCLUSION: Biennial FOBT screening improves detection of colorectal cancer at the first screening round, but the high percentage of interval cancers is a cause for concern.

Surgery for peptic ulcer today. A study on the incidence, methods and mortality in surgery for peptic ulcer in Finland between 1987 and 1999.

BACKGROUND: During the past 20 years medical therapy of peptic ulcer disease (PUD) has dramatically improved. Simultaneously there has been a significant improvement in living and dietary habits. Quite presumably, all these significant events are reflected in the incidence and results of surgery for peptic ulcerations. AIM: To study the incidence, methods and mortality of surgery for PUD. METHODS: The nationwide data between 1987 and 1999 were obtained from the National Research and Development Centre for Welfare and Health. In the analysis the codes of the ICD 9-10 were used. RESULTS: The annual incidence of elective surgery for PUD decreased from 15.7 to 1.7 operations (per 10(5) inhabitants, mean of 2 consecutive years) between 1987 and 1999 (p < 0.05). Simultaneously, the annual incidence of emergency surgery increased from 5.2 to 7.0 operations (per 10(5) inhabitants, p < 0.05). In 1987, local procedures (duodeno-/gastrorrhaphy or duodeno-/gastrostomy and suture) were applied in 25% of operations for PUD, whereas in 1999 they were 90% of the methods in PUD surgery. The overall annual mortality from PUD surgery remained 8% between 1987 and 1999. CONCLUSIONS: Elective ulcer surgery has virtually disappeared and parietal cell vagotomy has become history, whereas the incidence of emergency surgery increased significantly between 1987 and 2000, with the exception of the most recent years. Local procedures are overwhelmingly applied in emergency surgery and more extensive surgery is unnecessary. Nevertheless, the overall surgical mortality remained 8% between 1987 and 1999.

Current features of peptic ulcer disease in Finland: incidence of surgery, hospital admissions and mortality for the disease during the past twenty-five years.

BACKGROUND: Medical therapy of peptic ulcer disease (PUD) has improved dramatically during the past 20 years with the introduction of modern antisecretory drugs as well as eradication therapy of Helicobacter pylori. During the 1990s, there has been a 3-fold increase in the consumption of histamine-2-receptor antagonists and proton-pump inhibitors, but also an 8-fold increase in the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) in Finland. METHODS: The incidence of surgery, hospital admissions and mortality for PUD was analysed between 1972 and 1999; the data were collected from the National Research and Development Centre for Welfare and Health and from the National Centre for Statistics. In the analysis, the codes of the Intemational Statistical Classification of Diseases 8-10 were used. RESULTS: In 1987, 11.9 elective operations (per 10(5) inhabitants) were performed (mean of 2 consecutive years), but only 1.3 in 1997, a reduction of 89%. In 1987, 5.2 emergency operations for ulcer perforation or bleeding were performed, whereas there were 7.5 in 1997, an increase of 44%. The annual hospital admission rate increased from 38.3 admissions (per 10(5) inhabitants) in 1972 (mean +/- s (standard deviation) of 5 consecutive years) to 68.7 in 1992. This 79% increase was mainly due to bleeding from gastric ulcer in elderly women. The overall annual mortality rate increased between 1972 and 1992 from 6.4 to 8.4 deaths (per 10(5) inhabitants), i.e. by 31%. The mortality rate from ulcer perforation and haemorrhage increased from 4.2 deaths in 1972 to 7.3 deaths in 1992, i.e. by 74%. CONCLUSIONS: The increasing incidence rates of emergency surgery, hospital admissions and mortality for PUD in the 1980s and 1990s have started to decrease in the most recent years in Finland. This epidemiologic change probably reflects both the demographic change and an increased consumption of NSAIDs, among the elderly people, in particular. The most recent epidemiologic change may reflect an increased consciousness about the harmful effects of conventional NSAIDs. Regardless of the constantly occurring emergency surgery, elective surgery for PUD is hardly ever required today.

Induction of proliferation in isolated guinea pig gastric epithelium during restitution after superficial injury.

Immediate repair of the gastrointestinal epithelium after superficial injury is called restitution. It is based on the migration of the surviving mucoid neck cells over the area of injury. The involvement of growth factors in the process has been recently documented. They are known to enhance the process (ie, EGF, FGF, TGF-beta) and to activate the basolateral Na+-H+-antiport (EGF). They may exert their effect by activating intracellular tyrosine kinases or by inducing chemotaxis. Yet, their precise mechanism of action in the process is unknown. The aim of the present study was to investigate the effect of modulation of the signal transduction pathway on the occurrence of proliferative mucoid neck and foveolar cells in guinea pig gastric epithelium. Therefore guinea pig gastric epithelium was mounted in Ussing chambers in vitro and perfused 4 hr after superficial injury with 1.25 M NaCl. The potential difference over the epithelium and tissue resistance were recorded simultaneously. The tissue was exposed either to cycloheximide, genistein, or to 4-phorbol myristate 13-acetate (PMA) during the 4-hr recovery, and the expression of proliferative cells was assessed by staining the tissue for proliferative cells (Ki-67). The mean proliferative index of tissues subjected to NaCl injury was significantly higher than that of uninjured control tissues after 4 hr of restitution. Inhibition of the signaling pathway with genistein decreased the proliferative index significantly, while its stimulation with phorbol myristate increased it. Both electrophysiologic and morphologic restitution were sensitive to genistein, but not to PMA or cycloheximide. Superficial epithelial injury results in a significantly increased occurrence of proliferative cells in isolated guinea pig gastric epithelium. This endogenous activation of the tissue is sensitive to inhibition by tyrosine kinases and to stimulation by protein kinases. Electrophysiologic and morphologic recovery are also affected by the modulation of the signaling pathway. This suggests that it is involved in the immediate repair process.

Poor prognosis of gallbladder cancer persists regardless of improved diagnostic methods. Incidence and results of surgery during 20 years in Helsinki.

BACKGROUND AND AIMS: The ominous prognosis of primary gallbladder cancer is well-known. This study assesses whether the prognosis has improved, and whether the substantial development in the radiologic imaging techniques is reflected in the survival of these patients. MATERIAL AND METHODS: The series consisted of 122 patients operated on for primary cancer in the gallbladder in the Helsinki City area between 1970 and 1990. RESULTS: The mean age of the patients was 68.6 years and did not change during the period, but there was a significant proportional increase in male patients. Only 2% of patients had a localized disease at the time of diagnosis, and there was no improvement in the diagnostic sensitivity during the observation period. Yet, the number of unexpected postoperative cancer diagnoses increased from 4% to 15% during the two decades. The primary mortality decreased from 21% to 13%, the one-year survival increased from 7% to 13%, whereas the five-year survival remained unchanged. CONCLUSIONS: During the past two decades the frequency of surgery for primary gallbladder cancer has increased significantly among males in the Helsinki City area. Regardless of the improved immediate survival the long-term survival has remained poor. The marked development in radiologic techniques is not reflected in the prognosis of these patients. Even under conditions in which the potential for the diagnosis of a malignant gallbladder disease is available, the opportunities for radical surgery are not utilized maximally, which is a cause for concern.

Recent trends in mortality from peptic ulcer disease in Finland.

The enormous change of medical therapy of peptic ulcer disease in the 1970s has resulted in a significant decrease of elective ulcer surgery. It has been speculated whether this might be reflected in the mortality of the disease. Therefore, in the present study, the mortality rate of the disease was evaluated in Finland during the past 17 years covering the dramatic change in the medical therapy: the introduction of H2-receptor antagonists. This was done with a population-based epidemiological study by analyzing 1262 death certificates of people dying from peptic ulcer disease in Finland between 1972 and 1989. The study showed that there has been almost twofold increase in the mortality of the disease between 1972 and 1989 in Finland. This was mainly due to the significantly increased number of fatal ulcer hemorrhages in older people, but also mortality from ulcer perforations increased. This unfavorable epidemiological progress was most striking among elderly women and became manifest during the 1980s. We conclude that mortality from peptic ulcer disease has significantly increased in Finland due to fatal ulcer hemorrhages and perforations. This epidemiological change became manifest in the 1980s, concurrently with the dramatic change in the medical therapy of peptic ulcer disease.

Preepithelial mucus-HCO-3 layer protects against intracellular acidosis in acid-exposed gastric mucosa.

The role of the preepithelial mucus-HCO-3 layer in protection against intracellular acidosis was investigated in isolated Necturus gastric antral mucosa exposed to luminal acid by simultaneous measurement of intracellular pH (pH(i)) and extracellular surface pH (pHs) in surface epithelium with microelectrode technique. Acidification of the luminal perfusate to pH 2.5 acidified pH(i) in surface epithelial cells from 7.33 +/- 0.02 to 7.20 +/- 0.04, whereas pHs fell from 6.75 +/- 0.21 to 5.20 +/- 0.25 (P < 0.01; n = 9), followed by a steady state for at least 2 h. Inhibition of epithelial HCO-3 secretion and transport by removal of serosal HCO-3 and CO2 (HEPES and O2 substitution) during acid exposure provoked a progressive acidification of pHs from 5.60 +/- 0.41 to 2.74 +/- 0.14 in 30 min (P < 0.01; n = 9), which was accompanied, after a 5- to 10-min delay, by acidification of pH(i) from 7.21 +/- 0.03 to 5.68 +/- 0.26 (P < 0.01). Digestion of the surface mucus gel by pepsin (5% wt/vol) at pH 2.5 caused a slow acidification of pHs from 5.22 +/- 0.59 to 3.60 +/- 0.46 within 2 h. This was followed by a more rapid acidification to 2.53 +/- 0.38 (P < 0.01; n = 7), with concomitant acidification of pH(i) from 7.19 +/- 0.05 to 6.03 +/- 0.33 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Peptic ulcer surgery in the nineties: patient profile, immediate results and clinical findings.

The decreasing frequency of elective ulcer surgery and the persisting frequency of emergency surgery for peptic ulcer diseases has often been reported. The reason for the divergent epidemiological behaviour of the two subgroups of surgical candidates is not clear. The present cross-sectional, population-based analysis of patients undergoing peptic ulcer surgery evaluates the mode of preoperative therapy in elective and emergency cases. It also assesses the present frequency of peptic ulcer surgery, ulcer complications, and the immediate results of ulcer surgery in a target population. The evaluation concerned 117 adult patients (F/M ratio 1/1.1, mean age 58.7 +/- 1.8 years) operated on for peptic ulcer disease in Helsinki City between March 1990 and February 1991. The annual frequency of elective surgery was 8.3 and of emergency surgery 20.7 per 10(5) residents in Helsinki. 30% of the patients treated surgically had no preoperative symptoms or antiulcer medication; the others were on on-demand type H2-receptor antagonist therapy. Whereas there was no mortality from the elective surgery the mortality rate for the emergency surgery was 10%, mainly due to cardiopulmonary reasons among elderly, high-risk patients. In conclusion, since our previous report for 1987 for the same target population in Helsinki, the incidence of emergency surgery has additionally increased, while the incidence of elective surgery has continuously decreased.

Peptic ulcer surgery during the H2-receptor antagonist era: a population-based epidemiological study of ulcer surgery in Helsinki from 1972 to 1987.

To evaluate the effects of improvements in medical therapy on the incidence of, indications for and operative methods used in peptic ulcer surgery, all cases of primary peptic ulcer surgery among adults in the city of Helsinki in the years 1972, 1977, 1982 and 1987 were analysed. There was a total of 565 such cases in a population which consisted of 5.2 X 10(5) individuals in 1972 and 4.8 X 10(5) individuals in 1987. The introduction of H2-receptor antagonists in 1979 was associated with a fall in the annual incidence of elective duodenal ulcer operations, from 15.5 to 6.7 per 10(5) individuals, and a fall in the annual incidence of elective gastric ulcer operations, from 9.4 to 3.1 per 10(5) individuals (P less than 0.05). The decrease was greatest among males with duodenal ulcer. In contrast, the annual incidence of emergency surgery for ulcer haemorrhage and perforation (all types of ulcers) remained relatively stable, varying from 7.2 to 10.2 per 10(5) inhabitants over the observation period (n.s.). The mean age of patients undergoing elective surgery remained essentially unchanged. The mean age of patients undergoing emergency surgery increased. The decrease in the annual incidence of elective duodenal ulcer surgery occurred mainly in relation to proximal gastric vagotomy. There was a concomitant relative increase in the incidence of gastric resection. The types of operative procedures used in cases of pyloric, prepyloric and gastric ulcer remained unchanged over the years 1972 to 1987.

[Changes in ulcer surgery following introduction of H2-blockers]. / Förändrad ulcuskirurgi efter introduktion av H2-blockerare.

To determine the effect of modern drug treatment on the incidence and type of ulcer operations, a retrospective survey was made of ulcer surgery performed on adult Helsinki residents during the years 1972, 1977, 1982 and 1987, with regard to indications and types of surgery. The introduction of H2-receptor blockers in 1979 was followed by a marked reduction in the incidence of elective ulcer surgery. On a population basis, the annual incidence of duodenal ulcer (DU) operations diminished by 50 per cent over the period 1972-1987, and that of operations for gastric ulcer by about two thirds, the falling trend being most marked among male DU patients. Figures for emergency surgical intervention in cases of haemorrhage or perforation remained unchanged during the period, as did the mean age of patients admitted for elective surgery, though the mean age of patients undergoing emergency surgery manifested a rising trend. The number of patients undergoing elective surgery for DU diminished, a trend first and foremost attributable to the fact that proximal selective vagotomy was performed more rarely, while the number of resections increased. The incidence of surgical treatment of pyloric and gastric ulcers remained unchanged during the period.

The prognostic significance of radiologically determined gastric emptying time before proximal gastric vagotomy.

The importance of undisturbed pyloric function is known among surgeons applying proximal gastric vagotomy (PGV) for duodenal ulcer disease. On the other hand, the prognostic significance of subclinically impaired antroduodenal motility is unknown after this operation. Therefore, in the present study 43 PGV patients with normal gastric emptying were compared with 24 PGV patients with prolonged gastric emptying as to the postoperative incidence of ulcer recurrence and symptomatology. Prior to surgery gastric emptying time was determined radiologically in all patients, none of whom had symptoms or signs of gastric outlet obstruction. The duration of postoperative follow-up in the series was 8 to 11 years. The incidence of ulcer recurrence during follow-up was 16% in the whole series, being significantly higher among patients with the primary ulcer in the pyloric or prepyloric area than among those with the lesion in the duodenal bulb. Furthermore, in the patient group with a primary ulcer in the duodenum an excellent operation result was achieved significantly more frequently in the case of preoperatively normal gastric emptying than in the case of delayed emptying. The incidence of ulcer recurrence tended also to be higher among the duodenal ulcer patients with prolonged emptying than among those with normal emptying through the difference between the groups did not reach statistical significance. This study emphasizes the prognostic significance of unimpaired gastric emptying and of even minor subclinical motor dysfunction when electing PGV as the surgical treatment and also that radiologic determination of gastric emptying time before PGV is of value in all patients undergoing the operation, irrespective of the location of the primary ulcer.

Relation between serum group II pepsinogen concentration and the degree of Brunner's gland hyperplasia in patients with chronic renal failure.

Serum concentrations of group I and II pepsinogens (PG I and PG II) were determined in 15 patients with chronic renal failure. Gastroduodenoscopy with biopsy and acid secretion tests were also performed. Five patients had histologically confirmed severe Brunner's gland hyperplasia manifesting as multiple polyps in the duodenal bulb. Five patients had a mild form of Brunner's gland hyperplasia which was evident only by histological analysis. Five had no signs of such alterations. The three groups of patients were comparable in age, sex, mean level of serum creatinine, mean duration of dialysis treatment, distribution of non-dialysed and dialysed patients, and gastric histology. In patients with severe Brunner's gland hyperplasia the mean serum PG II concentration was significantly higher than in the other patients. Both the serum PG I and the serum PG II concentrations decreased after receiving a well functioning renal transplant in the two patients who underwent transplantation.

The effect of renal transplantation on gastric acid secretion and on the serum levels of gastrin and group I pepsinogens.

To gain further understanding of the peptic complications encountered in renal transplant surgery, 84 patients (19 with chronic renal failure on dietary treatment, 29 on regular dialysis treatment, 36 with a well-functioning renal transplant) were studied with regard to gastric acid secretion capacity and serum concentrations of gastrin and group I pepsinogens (PG I). The mean duration of preoperative dialysis treatment of the dialysed patients was 13.7 months. The mean length of postoperative follow-up of the transplant patients was 10.1 months. There was no significant difference between the mean gastric acid secretion of the three groups of patients. All the means were within the reported reference interval for healthy controls. However, 26% of the non-dialysed, 17% of the dialysed and 28% of the transplant patients had gastric hyposecretion. The mean serum concentration of gastrin was elevated in all patient groups and unaffected by normalization of renal function through transplantation, unlike PG I, which was normalized by the procedure. Thus, in the present era of treatment of chronic renal failure with a relatively short period of dialysis treatment, the frequent gastric hypoacidity, which is known to be peculiar to non-dialysed uraemic patients, seems also to characterize dialysis and transplant patients.

Multiple duodenal polyps in uraemia: a little known clinical entity.

Multiple duodenal polyps were found by endoscopy in five out of 33 patients with chronic renal failure and in one of 300 controls. In the uraemic cases the polyps were caused by circumscribed nodular hyperplasia of Brunner's glands. One of these five patients later underwent surgery for duodenal obstruction caused by the polyps; the other patients were asymptomatic. One of the controls had multiple duodenal polyps. The recorded incidence of multiple duodenal polyps was significantly higher among patients with chronic renal failure than in patients without renal disease. Patients with chronic renal failure and polyps did not differ significantly from the other renal patients in the comparison of variables such as gastric acid secretion, serum concentrations of gastrin and group I pepsinogens or mean length of dialysis treatment. The mean pH of gastric resting juice was significantly higher, however, in uraemic patients with polyps than in those without. Uraemic patients displayed a gastric acid secretion capacity within normal range, and significantly raised serum gastrin and group I pepsinogen concentrations.

Ranitidine and cimetidine in renal transplantation: a clinical trial.

Sixteen patients were randomized for treatment with ranitidine and seventeen for treatment with cimetidine to prevent the appearance of upper gastrointestinal (UGI) complications after renal transplantation. The two operated groups were comparable with regard to age, sex, number of pre-operative blood transfusions, and HLA match. All patients were treated with a similar immunosuppressive regime, consisting of azathioprine and methylprednisolone, and underwent endoscopic examination ten and thirty days following surgery. In the second endoscopy an entirely normal condition was observed in 11 and 12 cases in the oesophagus, 4 and 4 cases in the stomach and 13 and 12 cases in the duodenum in the two groups of 16 and 17 patients respectively. Except for one uncomplicated prepyloric ulcer in the cimetidine group, the remaining endoscopic findings were mild in intensity. There were, however, significantly more rejection episodes in the cimetidine group than in the ranitidine group. Ranitidine seems to be a safe drug in transplant patients, but the high incidence of rejection episodes in the cimetidine group is a cause for concern.