Antenatal ultrasound and postnatal autopsy findings in terminations after 12 weeks' gestation due to fetal abnormality: population-based study in Western Norway, 1988-2002.

BACKGROUND: Ultrasound screening has been part of antenatal care for several decades, and warrants high expertise to meet the criteria for a worthwhile screening program. In particular, the rate of false positives should be low. PURPOSE: To examine time trends of pregnancy terminations for fetal abnormality after 12 weeks' gestation, and to assess the agreement between antenatal ultrasound and post-termination autopsy findings for the main pathologies leading to termination. MATERIAL AND METHODS: During the period 1988 to 2002, 198 pregnancies were terminated for fetal abnormality after 12 weeks' gestation. We reviewed the case notes for those 151 who were autopsied (male/female/undetermined ;= ;91/56/4). Annual rates of live births and stillbirths were retrieved from the Medical Birth Registry of Norway. RESULTS: Antenatal ultrasound provided a correct diagnosis of the major abnormality in 149/151 cases (99%), based on post-termination autopsy findings. The annual rate of terminations after 12 weeks' gestation varied between 0.6 and 3.4 (mean 1.8) per 1000 live births, with a trend toward higher rates over the study period (P=0.001, chi-square test for linear-by-linear association). CONCLUSION: The specificity of antenatal ultrasound for major abnormalities was high, as compared to postnatal autopsy findings. The mean annual rates of termination after 12 weeks' gestation tended to increase over the 14-year study period.

Local resection of rectal tumors by transanal endoscopic microsurgery: experience with the first 70 cases.

BACKGROUND: Transanal endoscopic microsurgery (TEM) can access the whole rectum up to 20 cm from the anal verge. Due to its excellent view and accurate dissection, TEM is useful for the removal of adenoma and selected low risk cancers of the rectum. We report our experience with the first 70 patients presenting. METHODS: A prospective descriptive study of 70 patients treated for rectal tumor with TEM from December 99 until October 2002 at Haukeland University Hospital. RESULTS: TEM was performed in 37 men and 33 women, median age 70.5 (19-90) years, for anticipated adenoma (n = 64), adenocarcinoma (n = 3), rectal ulcer (n = 1), and re-resection after snare resection of rectal polyp with adenocarcinoma (n = 1) and carcinoid tumor (n = 1). The median observation time was 12 (1-33) months. The distance from the anal verge to the lower tumor border was 5.5 (2.5-14) cm. The median resected area was 15.4 (1.5-132) cm(2). 56 of the 64 anticipated adenomas were true adenoma, resected without recurrences; 8 (12.5%) were unexpected adenocarcinoma. Three of these underwent a secondary rectal resection and 5 patients have been observed without recurrence. Of the 3 patients with known adenocarcinoma, there was one recurrence which was treated with a secondary curative rectal resection. CONCLUSIONS: TEM can access tumors in the whole rectum. Large tumors may be removed with low frequency of per- and postoperative complications and short hospital stay. TEM is highly useful for removal of rectal adenoma. A role for primary treatment of selected low-risk rectal cancers may emerge.

Diagnostic value of radiography in cases of perinatal death: a population based study.

OBJECTIVE: To examine the yield of radiographic abnormalities in a population based set of perinatal deaths, the diagnostic value of whole body postmortem radiographs in the same set, and previous factors that may increase the proportion of useful examinations. DESIGN: Retrospective population based study. SETTING: A region of Norway. PATIENTS: All infants from a well defined geographical area who were stillborn or had died soon after birth over an 11 year period (n=542), who had routinely undergone whole body radiography and autopsy. MAIN OUTCOME MEASURES: (a) Proportion of cases with abnormal radiographic findings. (b) Proportion of abnormal radiographs providing new information that was useful for postmortem diagnosis. RESULTS: Radiographs were abnormal in 162/542 cases (30%). These provided new information about, but did not help to confirm, the pathological process leading to death in 14/162 (8.6%), may have helped to confirm, but not establish, the cause(s) of death in 1/162 (0.6%), and were of vital importance for establishing the cause(s) of death in 5/162 (3.1%). Among infants with external malformations, the proportion of useful radiographs was 12/100 (12%), and among the remainder it was 8/436 (1.8%), a difference of 10.2% (95% confidence interval 3.7% to 16.7%; data missing for six cases). CONCLUSIONS: The diagnostic value of postmortem radiography in this population based set was low. However, radiographic findings were of vital importance for establishing the cause(s) of death in 5/542 cases (0.9%).

The long-term outcome in patients with superficial transitional cell carcinoma of the bladder: a single-institutional experience.

OBJECTIVE: To determine the natural history of transitional cell carcinoma (TCC) of the bladder, and to identify factors which place patients at lifelong risk of developing progression and dying from bladder carcinoma. PATIENTS AND METHODS: The long-term outcome was evaluated retrospectively in 231 patients with superficial bladder TCC, assessed for the first time within a 6-year period from 1981 to 1986, with a median follow-up of 108 months. Of 231 patients, 217 (94%) were initially treated by transurethral or segmental resection. RESULTS: Recurrence developed in 141 of 217 (65%) patients; the duration of the interval free of recurrence was significantly less for patients with initial G3 tumours than that for those with G1 (P<0.01) and for pT1 compared with pTa disease (P<0.01). The disease progressed in 42 of 231 (18%) patients. Differences in the progression-free interval between patients with G1 and G3 tumours, and with pTa and pT1 disease, were statistically significant (P<0. 005 and P<0.001, respectively). In 27 of 231 patients (12%), TCC of the bladder was the cause of death, whilst 118 (51%) died from unrelated causes. There were no deaths among patients with initial pTaG1 tumours, compared with 10 of 26 (38%) deaths in those with pT1G3 disease at presentation. CONCLUSION: The long-term prognosis is good for patients with pTaG1 tumours, whilst pT1G3 is a potentially aggressive disease. Lifelong endoscopic surveillance is mandatory in patients in whom new tumours are very active, at least in those of younger age. Routine cystoscopy can possibly be discontinued in patients with low-grade, low-stage disease in whom a low liability of recurrence has been shown during follow-up.

Effect of cimetidine on development of gastric cancer in rats after gastrojejunostomy.

OBJECTIVE: To find out if cimetidine has an immunomodulating effect on gastric carcinogenesis in rats. DESIGN: Experimental prospective study. SETTING: Teaching hospital, Norway. ANIMALS: 132 male PGV/Mol rats given gastrojejunostomies. INTERVENTION: Half the rats were given cimetidine in their drinking water postoperatively for a minimum of 38 weeks. They were killed after 52 weeks observation and the stomach was investigated macroscopically and microscopically. MAIN OUTCOME MEASURE: In the cimetidine fed group 19/48 animals developed cancer (49%), versus 12/43 (28%) in the control group (p = 0.24). CONCLUSION: Cimetidine had no immunomodulatory effect on the development of gastric cancer in rats.

Survival after radical treatment for transitional cell carcinoma of the bladder.

AIMS: To investigate survival after radical treatment for transitional cell carcinomas of the bladder. METHODS: This retrospective study included 135 patients with transitional cell carcinoma of the bladder undergoing radical cystectomy or radiotherapy at Haukeland Hospital, Bergen, Norway, during the period 1981-1986. Forty-five patients had cystectomy and 90 underwent external high-dose radiotherapy. RESULTS: The overall 5- and 10-year survival rates were 39 and 23%, respectively. After cystectomy 10-year overall survival rates for superficial and muscle-infiltrating tumours were 67 and 26%; after radiotherapy, the corresponding survival rates for superficial and muscle-infiltrating tumours were 26 and 5%, respectively. CONCLUSIONS: Long-term survival and cure can be achieved after cystectomy in many patients with aggressive superficial or muscle-infiltrating bladder carcinoma. The introduction of orthotopic neobladder reconstruction should encourage the use of cystectomy in patients with aggressive superficial tumour.

Cell division in placentas of appropriate and small-for-gestational-age infants. A flow cytometry study.

BACKGROUND: The purpose of this study was to examine if placentas of small- for-gestational-age (SGA) and non-SGA infants differ with respect to proliferative cell activity. METHOD: Cell cycle distribution was studied in placentas from 181 SGA (birthweight < 10th percentile) and 528 non-SGA births by flow cytometry measurements of relative DNA content. RESULTS: The fraction of cells in various cell cycle phases (G1-, S- and G2-phases) did not differ with gestational age from 30 to 43 weeks in either of the groups. The placentas of the SGA infants had a significantly lower mean (+/-1 SEM) growth fraction than placentas of non-SGA infants (S-phase 5.2 +/- 0.2 vs 5.5 +/- 0.1, p = 0.05, and G2-fraction 5.4 +/- 0.2 vs 6.3 +/- 0.1, p < 0.001), but the overlaps of the distributions were large. Thus sensitivity, specificity and predictive values of low fractions did not differ substantially-from a purely random prediction of SGA. CONCLUSIONS: Cell division in the placenta is maintained until and beyond term. Placentas of SGA infants have on average, lower proliferative activity than placentas of non-SGA infants, but the difference is too small to be of predictive value in identifying intrauterine growth retardation.

Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole.

BACKGROUND: Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition. AIMS: To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole. PATIENTS AND METHODS: Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15-73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland. RESULTS: Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p < 0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p < 0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment. CONCLUSIONS: A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.

The prognostic value of p53 in superficially infiltrating transitional cell carcinoma.

Approximately 1/3 of T1 bladder cancers treated by endoscopic resection alone will progress. Prognostic factors are needed to help selecting appropriate treatment for these tumors. The purpose of the present investigation was to study the relation between p53 nuclear overexpression and disease progression. Tumors from 59 patients were studied by means of immunohistochemical nuclear staining. Forty tumors showed p53 nuclear overexpression while 19 tumors scored negative for mutations. We could not demonstrate any correlation between mutations of the p53 protein and tumor grading. p53 nuclear overexpression was not related to disease progression.

Flow cytometric DNA and p53 analysis in superficially infiltrating bladder carcinoma.

Mutations in the p53 gene occur frequently in bladder cancers. Better prognostic factors are needed to help select appropriate treatment for patients with TCC stage T1. Paraffin-embedded tumors from 73 patients with TCC stage T1 were processed for two-parameter flow cytometry, measuring both p53 protein and DNA. There were no statistically significant differences between the WHO grades with respect to p53 protein staining. Furthermore, there were no statistically significant differences between diploid, tetraploid and aneuploid tumors regarding content of mutant p53 protein. Neither were any statistically significant differences observed when ploidy and WHO grade were grouped together. Progression of disease was not correlated with positive p53 protein staining. These results indicate that mutant p53 protein cannot be used as a prognostic factor in TCC stage T1.

Prognostic importance of radical lymphadenectomy in curative resections for gastric cancer.

OBJECTIVE: To evaluate the effect of extensive lymphadenectomy on survival in patients with gastric cancer. DESIGN: Retrospective analysis SETTING: University Hospital, Norway. SUBJECTS: 183 patients with stomach cancer resected for cure during the time period 1980-90. INTERVENTIONS: 78 patients had an R1- and 105 patients and R2 resection. 124 patients were treated by total gastrectomy, 5 by proximal--and 54 by distal resection. MAIN OUTCOME MEASURES: Morbidity, mortality and long term survival. RESULTS: The morbidity was 33% (60/183), of which 39 (21%) were general complications (pneumonia, thrombosis, or cardiovascular disease). 14 patients died postoperatively (8%). By logistic regression analysis we found that splenectomy was the only variable associated with both morbidity and immediate postoperative mortality. Five year survival was 39% for patients who had undergone curative resections, 30% for patients who had had an R1 resection, and 47% for those who had had an R2 resection. By multivariate analysis (Cox) we found that N-classification (TNM), tumour diameter of less than 45 mm, type of lymph node dissection (R2) and operation period (after 1984) correlated with improved survival. CONCLUSION: Extensive lymph node dissection improves survival without increasing morbidity or postoperative mortality.

The influence of the host on the course of gastric carcinoma.

Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with recurrence than in 46 5-year survivors. The prognostic significant of C1-INH was superior to that of the extent of disease (F-values 37.1 and 26.1). The preoperative immune data classified 76% of the patients correctly as to recurrence and no recurrence. Also, the preoperative C1-INH concentration had a highly significant effect on time to recurrence of cancer (P = 0.0007), adjusting for age and disease extent. After surgery the mean IgG concentrations were within normal range and without difference between the two groups. On the other hand, the concentrations of C1-INH and C4 in the individual patients in both groups remained the same from before to after surgery and throughout the observation period (P = 0.34). Apparently, the serum levels of C1-INH and C4 do not reflect the bearing of cancer. We therefore suggest that these variables represent an independent immune state that is appropriate to the host. A comparison of our variables with those of healthy individuals seems to support this idea. This immune state has a significant influence on whether a resected gastric cancer will recur, and also on how soon recurrence may be manifest.

Is Lauren's histopathological classification of importance in patients with stomach cancer? A national experience. Norwegian Stomach Cancer Trial.

This study was performed to investigate the association between Lauren's histopathological classification system and different clinico-pathological characteristics in patients with gastric carcinoma. We revealed that the percentage of intestinal type tumour (ITT) increased with advancing age (52% in patients less than 60 years compared to 73% of octogenarians (P less than 0.001)). The male:female ratio was 1.7 for ITT versus 1.3 for diffuse type tumour (DTT (P = 0.12)). ITT was more common in proximally (fundus) localized tumours than in distal lesions (77% vs 65%; P less than 0.05). The proportion of patients with ITT decreased with advancing stages of the disease (70% in stage I and II vs 52% in stage IV (P less than 0.0001)). More patients with DTT had tumour infiltration in the resection margin (21% vs 9%; P less than 0.001). Intestinal metaplasia was found in 48% of those with ITT compared with 28% of those with DTT (P less than 0.001). No association was found between Lauren's classification and the ABO blood group or between the tumour types and infiltration in lymphatic or blood vessels. We conclude that gastric adenocarcinoma occurs in at least two different biological forms and that differentiation between the two is of relevance for treatment.

The influence of age on the growth and spread of gastric carcinoma.

A twelve year series of 375 patients with gastric carcinoma has been studied. Patients were divided into TNM Groups. Tumours were classified as intestinal-type and diffuse. The patients with T1-3NOMO diffuse tumour were ten years younger than the patients with T1-3NOMO intestinal-type tumour. The mean age increased from T1 through T2 to those with T3 tumour. The age differences between the T-stages were the same in both groups, which indicate that once started, the diffuse and the intestinal-type tumours infiltrate the gastric wall at about the same rate. Among the patients with intestinal-type tumour, those with lymph node or distant metastases were three to seven years younger than the patients without metastases. On the other hand, the patients with diffuse tumour and metastases were as many years older than the patients without metastases. Apparently, tumour spread is age dependent and different between the two types of gastric carcinoma. The ill repute of the diffuse gastric carcinoma may therefore be explained by the advanced stage of that tumour at the time of treatment as compared to the intestinal-type tumour. The diffuse tumour seems to be clinically more silent and to give symptoms at a later stage than the intestinal-type tumour.

Age and sex distribution of intestinal type and diffuse gastric carcinoma.

A twelve-year series of 375 patients with gastric carcinoma has been studied. Primary tumours were classified as intestinal type (58%) or diffuse (26%), whereas 16% were unclassifiable. The relative age and sex incidence rates of intestinal type and diffuse gastric carcinoma were estimated using the age and sex distribution of individuals in Norway as the basis for calculation. There was no difference in the rates of diffuse gastric carcinoma between the sexes. On the other hand, the rate of men with intestinal type carcinoma was more than twice as high as that of women. This difference was consistent within each age group from adolescence to senescence. The findings indicate that Laurén's two types of gastric carcinoma are aetiologically different. The rates of both types increased with age up to the 70-79 age group, whereas the rates in octogenarians tended to be lower than in septuagenarians. A comparison of our data with the data of incidence of gastric cancer in Norway indicates that some of the older patients do not come for surgery.

Periodicity in metastatic tumour growth demonstrated in the human liver at autopsy. Preliminary report.

The present study is based on 1,069 autopsies made up of stomach, breast, renal and colonic cancer. Periodicity is described in the liver weight index (liver weight/body height) at death in patients with liver metastases. The seasonal variation tended to be more marked in females and among older patients, and it differed with tumour type. A period with maximum deaths tended to follow that of maximum liver weight index. A periodic difference previously reported in a small series of malignant melanomas is thus not an isolated phenomenon. This indicates that basic biological pathways concerned with the control of tumour growth may be involved. How the system works remains an open question.

Underdiagnosis of carcinoma of the stomach in the elderly: a 25-year autopsy study.

Gastric carcinoma may present atypically in the elderly. Between 1955 and 1979, 571 autopsies on gastric carcinoma cases were carried out at the Gade Institute, Bergen. In 165 of them the diagnosis had not been made clinically. The latter patients were, on average, 10 years older at death than those in whom the diagnosis was made premortem, and their tumours were smaller. In 45 the tumour was considered an incidental autopsy finding, while 58 were diagnosed clinically as advanced cancer of unknown origin. In the remaining 62 cases the cancer was the underlying cause of death. Recognition of an elderly sub-group of patients whose gastric carcinomas presented atypically brings with it an increasing diagnostic challenge in our ageing population.

Who gets a second primary cancer after gastric cancer surgery?

Eleven patients presented with a second primary cancer during follow-up after surgery for gastric carcinoma. In these patients the serum concentrations of C1-INH and IgG prior to gastric cancer surgery were similar to those of 53 patients with recurrence of gastric cancer. In these two groups, the preoperative C1-INH concentrations were higher and IgG lower (P less than 0.001 and P less than 0.05) when compared to 36 patients alive and disease-free 5 years after surgery. The median time between surgery and signs of recurrence was 11 months, whereas the median time until signs of the second primary cancer was 4 years. A patient with gastric carcinoma who pre-operatively has high C1-INH and low IgG is liable either to have recurrence or to develop a second primary cancer. Our data indicate that these variables represent a cancer susceptibility feature appropriate to the host.

Serum C1-esterase inhibitor, an essential and independent prognosticator of gastric carcinoma.

The preoperative concentrations of IgG were lower (P less than 0.002) and the concentrations of C4 and C1-INH higher (P less than 0.01 and P less than 0.001) in 29 patients with recurrence after potentially curative resection of gastric carcinoma, than in 31 patients alive and disease-free 5 years after surgery. These differences between the two groups of patients were consistent within each of six groups of disease extent. In each of the two groups of patients, the preoperative concentrations of IgG, C4 and C1-INH had no significant variation with the extent of disease (P greater than 0.05 or greater). Of our variables, C1-INH was the most potent prognosticator and discriminated between patients with and without recurrence with 80% accuracy. Furthermore, the predictive prognostic value of C1-INH at the time of surgery was superior to the prognostic value of the extent of disease (F values 27.00 and 12.69). Apparently, the preoperative C1-INH concentration is an essential and independent prognostic parameter of gastric carcinoma. We assume that C1-INH reflects an additional prognostic feature appropriate to the tumour or the host. Our finding that the interval between surgery and death from recurrence had an inverse relation to the preoperative C1-INH concentration also supports this assumption.

Preoperative prediction of extent and prognosis of gastric carcinoma by four serum proteins and erythrocyte sedimentation rate.

In 195 patients with gastric carcinoma the preoperative ESR and serum concentrations of IgG, C4, C1-INH and CEA varied significantly with the extent of disease. Extent of disease and prognosis were predicted from these variables by discriminant analysis. The discriminant rules were tested on the same patients in an unbiased way. Metastases or no metastases were correctly predicted in 75% of the patients. By an appropriate prior distribution 93% of the patients without metastases were identified. The disease extent was also predicted in subgroups of patients with and without metastases. Survival was correctly predicted preoperatively in 66% of the patients and 83% of the patients with a fair prognosis were identified. Of the patients preoperatively allocated to the non-survival group 94% did actually die during follow-up. When used in addition to other available information, our discriminant rules will contribute to the quality of the preoperative evaluation of patients with gastric carcinoma.