Objectives: To study the role of platelet-activating factor (PAF) on cardiovascular and pulmonary dysfunction in sepsis and shock.

Design: Experimental study. Setting: Trauma research unit, university department of surgery, Sweden.

Material: 76 juvenile domestic pigs. Interventions: The effects of a specific PAF receptor antagonist (BB-882) on haemodynamics and on PAF-induced haemodynamic changes were studied (n = 16). BB-882 was given as pretreatment in non-hypotensive Escherichia coli endotoxaemia (n = 9), during resuscitation after severe haemorrhagic shock (n = 7), hefore post-ischaemic shock which was induced by clamping the aorta above the coliac axis for 45 minutes (n = 8), and as pretreatment in post-haemorrhage septic shock: (n = 6). BB~882 groups were compared with controi groups having the same number of animals which received vehicle instead.

Major outcome measures: Heart rate, intravascular pressures, cardiac output, pulmonary and systemic vascular resistance, arteriai blood gas tensions, lung thorax compliance, serum lactic acid and blood sugar concentrations, and packed cell volume.

Results: BB-882 effectively counleracted the PAF-induced response on the mean systemic and pulmonary arteriai pressures. lt reduced the rise in pulmonary and systemic vascular resistance and improved the cardiac output in non-hypotensive and post-haemorrhage septic shock when given as pretreatment. lt reduced the hypertension in non-hypotensive sepsis and the hypotension in post-haemorrhage septic shock. BB-8B2 did not infiuence the endotoxin-induced hypoxia or reduced lung thorax compliance in non-hypotensive sepsis and post-haemorrhage septic shock. It did not improve the mean arterial pressure or the cardiac output in haemorrhagic shock alone but it reduced the systemic vascular resistanc'e and was associated with tachycardia and acidosis. It did not affect the post-ischaemic shock after clamping the aorta.

Conclusion: PAF is a major mediator of the cardiovascular, but not pulmonary dysfunction in sepsis whether associated with shock or not, while its role on the cardiovascular dysfunction in haemorrhagic and post-ischaemic shock is small.

BACKGROUND: Rectal carcinoma is a common malignancy, with a history of high local recurrence rates following surgery. In recent years. preoperative radiotherapy and refined surgical technique have improved local control rates.

AIM: To investigate the relationship between expression of nuclear p53 protein and the outcome in rectal carcinoma, with and without short-term preoperative radiotherapy.

MATERIAL: Specimens from 163 patients from the Southeast Swedish Health Care region included in the Swedish rectal cancer trial between 1987-1990.

METHOD: New sections from the paraffin blocks of the preoperative biopsy and the surgical specimen were examined immunohistochemically using a p53 antibody (PAb 1801).

RESULT: Expression of nuclear p53 protein was seen in 41% of the tumours. The p53 negative patients treated with preoperative radiotherapy had a significant reduction of local failure compared with the non-irradiated p53 negative patients (P = 0.0008). In contrast, p53 positive patients showed no benefit from preoperative radiotherapy. The interaction between p53 status and the benefit of radiotherapy was statistically significant (P = 0.018).

CONCLUSION: Expression of nuclear p53 protein in rectal carcinoma seems to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Further investigations are necessary to select patients for preoperative treatment based on analysis of the preoperative biopsies.

Background. Optimal treatment for low rectal cancer is total mesorectal excision, with most patients suitable for low colo-rectal or colo-anal anastomosis. A colon pouch has early functional benefits, although long-term function, especially evacuation, might mitigate against its routine use. The aim of this study was to assess evacuation and continence in patients with a colon pouch, and to examine the impact of possible risk factors. Methods. In 1998, all 102 surviving patients with a colon pouch, whose stoma had been closed for more than one year, were sent a postal questionnaire. A composite incontinence score was calculated from questions on urgency, use of a pad, incontinence of gas, liquid or faeces, and a composite evacuation score from questions on medication taken to evacuate, straining, the need and number of times returned to evacuate. Results. The response rate was 90% (50 M, 42 F), with a median age of 68 years (IQR 60-78) and median follow-up of 2.6 years (IQR 1.7-3.9). The anastomosis was 3 cm or less from the anus in 45/92 (49%), and incontinence scores were worse in this group (P = 0.001). There were significantly higher incontinence scores in females (P = 0.014). Age, preoperative radiotherapy, part of colon used for anastomosis, post-operative leak and length of follow-up had no demonstrable effect on either score. Conclusion. Gender and anastomotic height were the only variables which influenced incontinence. Ninety percent of patients reported that their bowel function did not affect their overall wellbeing, and none would have preferred to have a stoma.

Preservation of normal parathyroid function and calcium homeostasis after operations on the thyroid and parathyroid glands is a difficult assignment in endocrine surgery, and it is crucial to minimise the risks of permanent postoperative hypoparathyroidism. The aim of this thesis was to study the vascular supply of the parathyroid glands and the revascularisation, growth, and function of transplanted parathyroid tissue, in order to add new information about parathyroid preservation.

The microcirculation and blood supply of normal, hyperplas~c and adenomatous parathyroid glands were studied with laser Doppler flowmetry in 103 patients during operations on the thyroid and parathyroid glands. In normal parathyroid glands the blood flow was higher compared with that in hyperplastic glands and adenomas. Occlusion of the main trunks of the inferior and superior thyroid arteries reduced the blood flow by 35% and 25%, respectively. The reduction was similar in normal, hyperplastic, and adenomatous parathyroid glands. In 12 patients with single parathyroid adenomas, the increased concentration of parathyroid hormone (PTH) remained mainly unchanged despite appreciable reduction in blood flow. In 16 patients the microcirculation and macroscopic appearance of normal parathyroid glands located anteriorly on the thyroid lobe were analysed before and after dissection for in situ preservation. There was a poor correlation between reduction in blood flow and macroscopic appearance of the glands. Laser Doppler flowmetry (LDF) showed that the disturbed microcirculation often recovered 30-60 minutes after dissection for preservation.

Parathyroid tissue obtained from 47 patients operated on for hyperparathyroidism was implanted subcutaneously in athymic mice. The processes of revascularisation, morphology, cell proliferation, and function of normal, hyperplastic, and adenomatous parathyroid tissue were studied at 2 and 4 days and 1, 4, 7 and 12 weeks after transplantation. Vessels were detected by monoclonal antibodies specific for mouse and human endothelial cells. The transplanted tissues were examined by light and electron microscopy and by autoradiography after continuous infusion of tritiated thymidine. The relative amount of viable tissue was assessed with a computer image-analysing program. Graft function was judged by measuring human iPTH in mouse serum.

Over 90% of the transplants took and the original structure of the tissue was well preserved. Confluent areas of parathyroid tissue could be seen in 80% of the transplants. The mean loss of viable tissue in all three groups was 45%.

Immunohistochemical examination showed ingrowth of vessels from the host into the transplant. The sprouts matured gradually into vessels with thin endothelial linings and capillary fenestrations in adenomatous and hyperplastic transplants but not in transplants of normal tissue.

In normal parathyroid tissue the proliferation of parathyroid parenchyma! cells increased only slightly in contrast to the advancing proliferative capacity in adenomatous tissue. In contrast to adenomas, parenchyma! cell proliferative capacity in hyperplastic tissue decreased at 12 week.

Concentrations of iPTH were raised at one week in hyperplastic and adenomatous tissue. Twelve weeks after transplantation iPTH concentrations in relation to the amount of transplanted tissue and relative area of viable tissue were comparable in all three groups of transplanted tissue.

We conclude that, LDF is a feasible method to study physiological blood flow in human parathyroid glands. Parathyroid blood supply is not as dependent on the inferior thyroid artery as was previously suggested. LDF showed that blood flow recovered in parathyroid glands dissected for in situ preservation and any decision about autografting should be delayed until the end of the operation. Parathyroid transplants re vascularise from host vessels and this is more pronounced and proceeds faster in hyperplastic and adenomatous tissue than in normal transplants. In contrast to nonnal and hyperplastic transplants, adenomatous tissue has a greater and increasing proliferative capacity. The iPTH concentration as an expression of parathyroid function correlates poorly with parenchyma! cell proliferation.

The study concerns surgery in Crohn's disease, particularly Crohn's colitis, its relation to medical treatment, symptomatic load, perceived health, quality of life, outcome on anorectal function and also anorectal physiologic conditions.

Four hundred and thirty-two patients treated at the University Hospital, Linköping from 1970 to 1997 were included in the study. Operations and medical treatment were retrospectively reviewed, whereas symptomatic load, perceived health, quality of life, function outcome and anorectal physiology were prospectively evaluated.

In a cross-sectional analysis of all patients surveilled 1995 the annual incidence of surgery was 5.7% in a population-based cohort and 10.3% in referred patients. Medical maintenance treatment was used in 61 and 55% respectively. This led to 89% of the patients being in clinical remission or having only mild symptoms and to a large proportion with a perception of good health. The treatment was paralleled by a low rate of septic and surgical complications.

Surgical treatment of Crohn's colitis prior to 1990 mainly implied colectomy or proctocolectomy and thereafter almost exclusively segmental resection. The creation of a permanent stoma decreased and was rarely needed at the end of the study period when the annual risk was 0.23%. This development was basically due to a deliberate change in surgical attitude aiming at introducing similar treatment principles as for small bowel Crohn's disease With limited resections and preservation of transanal defecation. The reduced colectomy rate may have been facilitated by the introduction of immunosuppressive medical treatment as a reduction of colectomies tended to be associated with medical maintenance treatment during the later part of the study. Time from diagnosis to surgery was prolonged and stricture replaced active disease as the major indication for surgery. Symptomatic load and anorectal function outcome were better after segmental resection without the expense of an increased reresection rate. Seventy percent of patients with Crohn's colitis were in clinical remission and these patients scored quality of life similar to the general population but patients with active disease scored worse in all indexed aspects. The need of immunosuppression or previous surgery was not related to quality of life except when operated with a permanent stoma which negatively influenced psychological well being.

Anorectal physiology in Crohn's disease differed from controls with increased anal resting pressures and increased rectal sensitivity. This provides possible prerequisites for later development of anal pathology such as fissures and fistulas.

The study indicates that the concept oflimited surgery is applicable also in Crohn's colitis with obvious benefits for the patients. A treatment concept including medical maintenance treatment and limited resections implies that the vast majority of patients with Crohn's disease may live with only minor symptoms and minimal risk of having a permanent stoma, factors associated with a quality of life similar to that of the general population.

[No abstract available]

Objective  All treatment in Crohn's disease, although palliative, aims at restoring full health. The objective of this study was to compare health-related quality of life and psychosocial conditions in patients with Crohn's proctocolitis with a general population.

Patients and methods  One hundred and twenty-seven patients with Crohn's proctocolitis (median age 44 years, 44.1% men) were compared with 266 controls (median age 45 years, 50.7% men). A questionnaire consisting of the Short Form-36 (SF-36), the Psychological General Well-Being Index (PGWB) and a visual analogue scale (VAS) evaluating general health as well as questions regarding psychosocial conditions was used. Disease activity was evaluated by Best's modification of the classical Crohn's Disease Activity Index.

Results  Patients in remission had a health related quality of life similar to controls according to the SF-36 apart from general health where scores were lower (P < 0.01). Patients with active disease scored lower in all aspects of the SF-36 (P < 0.001 or P < 0.0001) as well as the PGWB (P < 0.0001). In a model for multiple regression including age, gender, concomitant small bowel disease, permanent stoma, previous colonic surgery, disease activity, duration, and aggressiveness, disease activity was the only variable negatively predicting all 8 domains of the SF-36 in the patient group (P < 0.001). The mean annual sick-leave for patients and controls were 33.9 and 9.5 days (P < 0.0001), respectively. Sixty-eight percent of the patients and 78.4% of the controls (P = 0.04) were married or cohabited, 67.7% and 78.0% (P = 0.04), respectively, had children.

Conclusion  The health related quality of life for patients with Crohn's proctocolitis in remission does not differ from the general population. The disease has, however, a negative impact on parenthood, family life and professional performance.

Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.

Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.

Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.

Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.

Background: This study describes how surgery for Crohn colitis developed between 1970 and 1997, towards the end of which period limited resection and medical maintenance treatment was introduced.

Methods: A cohort of 211 patients with Crohn colitis (115 population-based), of which 84 had a primary colonic resection (42 population-based), was investigated regarding indication for surgery, the time from diagnosis to operation, type of primary colonic resection, risk for permanent stoma and medication over four 7-year periods.

Results: Comparison of the periods 1970-90 and 1991-97 revealed that active disease as an indication for surgery decreased from 64% to 25% ( P < 0.01) while stricture as an indication increased from 9% to 50% ( P < 0.001). Median time from diagnosis to operation increased from 3.5 to 11.5 years ( P < 0.01). Proctocolectomy or colectomy fell from 68.8% to 10% of the primary resections, whereas segmental resection increased from 31.2% to 90%. At the end of the first 7-year period, 26% had medical maintenance treatment, steroids or azathioprine taken by 7%. Corresponding figures for the last period were 70% and 49%. Patients diagnosed during the last two time-periods had less risk for surgery ( P = 0.017), permanent stoma ( P < 0.01) and total colectomy ( P < 0.01). Findings were similar in the population-based cohort.

Conclusions: Current management of Crohn colitis implies a longer period between diagnosis and surgery, a reduced risk for surgery and permanent stoma, and the replacement of total colectomy by segmental resection.

PURPOSE: Anal pathology occurs in 20 to 80 percent of patients with Crohn's disease in which abscesses, fistulas, and fissures account for considerable morbidity. The etiology is not clearly defined, but altered anorectal pressures may play a role. This study was designed to investigate anorectal physiologic conditions in patients with Crohn's disease compared with healthy controls.

METHODS: Twenty patients with Crohn's disease located in the ileum (n = 9) or the colon (n = 11) without macroscopic proctitis or perianal disease were included. All were subjected to rectal examination, anorectal manometry, manovolumetry, and rectoscopy. Comparison was made with a reference group of 173 healthy controls of whom 128 underwent anorectal manometry, 29 manovolumetry, and 16 both examinations.

RESULTS: Maximum resting pressure and resting pressure area were higher in patients than in controls (P = 0.017 and P = 0.011, respectively), whereas maximum squeeze pressure and squeeze pressure area were similar. Rectal sensitivity was increased in patients expressed as lower values both for volume and pressure for urge (P = 0.013 and P = 0.014, respectively) as well as maximum tolerable pressure (P = 0.025).

CONCLUSIONS: This study demonstrates how patients with Crohn's disease without macroscopic proctitis have increased anal pressures in conjunction with increased rectal sensitivity. This may contribute to later development of anal pathology, because increased intra-anal pressures may compromise anal circulation, causing fissures, and also discharging of fecal matter into the perirectal tracts, which may have a role in infection and fistula development.

PURPOSE: Segmental resection for Crohn's colitis is controversial. Compared with subtotal colectomy, segmental resection is reported to be associated with a higher rate of re-resection. Few studies address this issue, and postoperative functional outcome has not been reported previously. This study compared segmental resection to subtotal colectomy with anastomosis with regard to re-resection, postoperative symptoms, and anorectal function.

METHODS: Fifty-seven patients operated on between 1970 and 1997 with segmental resection (n = 31) or subtotal colectomy (n = 26) were included. Reoperative procedures were analyzed by a life-table technique. Segmentally resected patients were also compared separately with a subgroup of subtotally colectomized patients (n = 12) with similarly limited colonic involvement. Symptoms were assessed according to Best's modified Crohn's Disease Activity Index and an anorectal function score.

RESULTS: The re-resection rate did not differ between groups in either the entire study population (P = 0.46) or the subgroup of patients with comparable colonic involvement (P = 0.78). Segmentally resected patients had fewer symptoms (P = 0.039), fewer loose stools (P = 0.002), and better anorectal function (P = 0.027). Multivariate analysis revealed the number of colonic segments removed to be the strongest predictive factor for postoperative symptoms and anorectal function (P = 0.026 and P = 0.013, respectively).

CONCLUSION: Segmental resection should be considered in limited Crohn's colitis.

[No abstract available]

Background: A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. Methods:We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. Results: Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87], for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90], and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06, 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). Conclusions: Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years.

In-hospital observation with repeated clinical examinations is commonly used in patients with an equivocal diagnosis of appendicitis. It is not known if repeated measurements of temperature and laboratory examinations have any diagnostic importance in this situation. The importance of repeated measurements of the body temperature, white blood cell (WBC) and differential cell counts, C-reactive protein concentration (CRP) and of the surgeon's repeated assessments was prospectively analyzed in 420 patients with an equivocal diagnosis of appendicitis at admission who were reexamined after a median of 6 hours of observation. The final diagnosis was appendicitis in 137 patients. After observation the inflammatory response was increasing among patients with appendicitis and decreasing among patients without appendicitis. The variables discriminating power for appendicitis consequently increased, from an area under the receiver operating characteristic (ROC) curve of 0.56 to 0.77 at admission, to 0.75 to 0.85 after observation. The ROC area of the surgeons' clinical assessment increased from 0.69 to 0.89. The WBC and differential cell counts were the best discriminators at the repeat examination. The change in the variables between the observations had weak discriminating power and had no additional importance in addition to the actual level at the repeat examination. To conclude, the diagnostic information of the temperature and laboratory examinations increased after observation. Repeated controls of the body temperature and laboratory examinations are therefore useful in the management of patients with equivocal signs of appendicitis, but the result of the examinations must be integrated with the clinical assessment.

Background & Aims: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. Methods: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. Results: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37, 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. Conclusions: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.

In this investigation colorectal cancer in the county of Östergötland has been studied with emphasis on risk factors, diagnostic efforts, and the results of treatment.

In two case-control studies on food and colorectal cancer, a decreased risk was associated with a high intake of cereal fibre, total fibre, and calcium per unit energy consumed as well as a high intake of raw vegetables. Processed meat was associated with an increased lisk for colon cancer and alcohol with an increased risk for rectal cancer. Drug consumption was also found to influence the cancer risk.

In a case-control study on occupational factors and the risk for colorectal cancer, some occupations seemed to influence the risk for colon and rectal cancer in different ways. Twenty years of physically active work significantly decreased the risk for left-sided colon cancer but increased the risk for rectal cancer. Accordingly, twenty year of sedentary work significantly decreased the risk for rectal cancer.

Known risk factors were found in 12% of colorectal cancer patients, though previous cholecystectomy did not turn out to be a risk factor.

The symptoms of colon cancer are vague and unspecific, whereas bleeding is prominent and a dominating symptom in rectal cancer. Conflicting results have been presented regarding the importance of a short delay between onset of symptoms and treatment. In our study, a more favourable stage distribution was found for rectal cancer with a very short delay between start of symptoms and treatment, but not for colon cancer.

Results of treatment for colorectal cancer show considerable variation in different series, which can be due to differences in selection and classification as well as in treatment. A computerized system for quality assurance of colorectal cancer was introduced in Östergötland in 1984. All cases diagnosed 1984-1986 were registered in this system, making it possible to study outcome of treatment for an unselected population. The results of treatment in terms of postoperative mortality and five year survival were comparable to the results from specialised international centres, but local recunence rate after operation for rectal cancer was high (20%).

To reduce this local recurrence rate, the technique of total mesorectal excision was introduced in three of the surgical departments in the county. Using the system for quality assurance, the local recunence rate during a three year period before the change in technique was compared with a three year period when the new technique was used. The local recunence rate was significantly reduced in the later period without any change in postoperative complications.

In conclusion this study shows an environmental influence on cancer-risk that may be different for colon and rectal cancer. The usefulness of a continuous quality assurance system to detect shmtcomings in diagnosis and treatment and to evaluate new techniques is also shown. Finally, total mesorectal excision reduces the local recurrence rate for rectal cancer in an unselected population treated in different kinds of hospital.

Breast cancer ≤ 10 mm together with ductal in situ cancer of the breast (DCIS) today constitute more than 40% of screening detected breast malignancies. Prognostic factors, diagnosis and clinical outcome for invasive breast cancers ≤ 10 mm and local recurrence in DCIS were evaluated.

Histopathological grading was done in 248 ductal breast cancers and grade III was correlated to aneuploidy, increased S-phase fraction and receptor negative tumours. Life table analysis showed a significant increase in breast cancer mortality in grade III tumours (p < 0.001).

Hormone receptors and cytometric variables were studied in ≤ 10 mm breast cancers. Around 60% of these small cancers were evaluable. Aneuploidy was found in 52% and SPF ≥ 10 in 20%. Mean SPF was 4.8 in diploid and 7.6 in aneuploid tumours. A potentially high risk group with high SPF figures and receptor negative tumours comprise 7% of the patients.

Diagnostic surgery was performed in 314 non-palpable breast lesions. Insufficient excisions were observed in 16 cases (5%), mostly in lesions with microcalcifications and in situ cancers ≥ 30 mm in extent. Underestimation of in situ cancers is the main reason for inadequate surgery.

DCIS comprises approx 10% of breast malignancies. In 38 cases operated with breast preserving surgery 13% got local recurrence in median 60 months follow-up.

Recurrence free survival in patients with ≤ 10 mm breast cancers were evaluated for 324 cases. Only 8% of these patients had adjuvant treatment. Lymph node involvement was found in 9% of screening detected and 20% in clinically detected cancers (p < 0.03). Median prospective follow-up time was 7 years and distant metastases appeared in 8 patients, local recurrence in 3. Life table analysis showed 97% overall distant recurrence free survival, 99% in node negative and 79% in node positive patients (p < 0.001).

We can today, by grading and cytometric variables, find subgroups with high risk of recurrence after breast cancer surgery in small breast cancers. These are probably the only patients that benefit from adjuvant treatment and need follow-up outside mammography screening. Breast conserving surgery can be performed in the majority of DCIS patients.

Background

Endothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.

Methods

Oxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [¹⁴C]aminopyrine.

Results

The histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors N^G-nitro-L-arginine methyl ester (L-NAME) or N^G-nitro-L-arginine (L-NNA) enhanced the secretory response.

Conclusion

Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.

We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [¹⁴C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

Previous studies have shown that nitric oxide (NO) inhibits histamine-induced gastric acid secretion in isolated human gastric glands. NO synthase has been found to be present in the human oxyntic mucosa and has been suggested to serve as a paracrine regulator of gastric acid secretion. Histamine stimulation of parietal cells induces cytoskeletal rearrangements, recruitment of H ⁺/K ⁺-ATPase-rich tubulovesicles to the apical membrane and expansion of intracellular canaliculi. The aim of the present study was thus to investigate (i) the effect of an NO donor on histamine-induced cytological transformations and (ii) the influence of increased [Ca ²⁺] _i on NO-induced morphological changes in human parietal cells. Human gastric glands were isolated and subjected to the NO donor SNAP prior to histamine administration. [Ca ²⁺] _i was increased by photolysis of the caged Ca ²⁺ compound NP-EGTA. The distribution of F-actin, ezrin, and H ⁺/K ⁺-ATPase was assessed by confocal microscopy. Ultrastructural analysis was performed using transmission electron microscopy. SNAP did not influence the histamine-induced translocation of F-actin, ezrin, and H ⁺/K ⁺-ATPase but prevented an increase in the canalicular size. Elevation of [Ca ²⁺] _i in resting cells was found to mimic histamine-induced intraparietal cell transformations; however, NO-induced parietal cell morphology was unaffected by a rise in [Ca ²⁺] _i. These results indicate that NO inhibits secretion of fluid into the canalicular lumen without affecting membrane recruitment and that this effect is Ca ²⁺-insensitive. © 2006 Springer Science+Business Media, Inc.

Aim: The aim of this study was to determine the prevalence of coeliac disease and its relation to duodenitis, H. pylori infection and gastritis in a sample of the adult general population. Methods: A Swedish population sample of 482 subjects (aged 35 to 85 years) were examined with gastro-duodenoscopy with multiple biopsies taken. Circulating antibodies to endomycium, gliadin, and H. pylori were also determined. Results: Based on histomorphological findings, coeliac disease was evident in 9 of 482 subjects giving a prevalence of 1.9 [1.0-4.0, 95% confidence interval] percent. The prevalence of gastritis with or without H. pylori infection did not differ between subjects with and without coeliac disease. Considering subjects without coeliac disease, there was no difference in the serum levels of gliadin antibodies between those with and without duodenitis. However, subjects with positive H. pylori status had significantly higher levels of gliadin antibodies than those with negative H. pylori status. Conclusions: This study confirms that there is a relatively high prevalence of undiagnosed coeliac disease in Swedish adults. There was no association between coeliac disease and H. pylori infection or gastritis, although serum gliadin antibody levels were slightly increased in subjects with positive H. pylori status.

Background: There are indications that some features of gastric carcinoma are changing, with a possible impact on prognosis. The aim of this study was to examine any changes in type, location, stage, resection rate, postoperative mortality rate or prognosis for patients with gastric carcinoma in a well defined population. Methods: During 1974-1991, 1161 new cases of gastric adenocarcinoma were diagnosed in Ostergotland County, Sweden. Tumour location, Lauren histological type, tumour node metastasis (TNM) stage, radicality of tumour resection and postoperative complications were recorded after histological re-evaluation of tissue specimens and examination of all patient records. Dates of death were obtained from the Swedish Central Bureau of Statistics. Time trends were studied by comparing the intervals 1974-1982 (period 1) and 1983-1991 (period 2). Results: The proportion of diffuse type of adenocarcinoma increased (from 27 to 35 per cent), while that of mixed type decreased (from 16 to 9 per cent) and that of intestinal type was unchanged. The proportion of tumours located in the proximal two-thirds of the stomach increased (from 32 to 42 per cent) and the proportion of patients with tumours in TNM stage IV decreased (from 32 to 25 per cent). Overall tumour resection rates were unchanged, although the proportion of radical total gastrectomies increased (from 36 to 50 per cent). Excluding tumours of the cardia or gastric remnant after previous ulcer surgery, the 5-year relative survival rate after radical resection increased from 25 to 36 per cent and the postoperative mortality rate decreased for both radical (from 11 to 4 per cent) and palliative (from 18 to 6 per cent) resection. Conclusion: The patterns of tumour histology, location and stage of gastric carcinoma have changed in the authors' region. These changes were paralleled by a significant improvement in survival and postoperative mortality rates.

Some benign and malignant diseases develop on the background of chronic gastritis or duodenitis. The present study was performed in order to determine the magnitude of these background changes with relations to symptomatology and life style in the general population. Examinations were performed in 501 volunteers (age 35–85 years). Fifty percent had gastritis; this was associated with H. pylori in 87%. H. pylori-negative gastritis was associated with regular use of NSAIDs [odds ratio 3.8 (1.6–9.9)]. Duodenitis, observed in 32%, was associated with H. pylori infection [odds ratio 2.3 (1.3–4.6)], previous cholecystectomy [odds ratio 3.6 (1.1–16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4–7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol consumption. The rate of digestive symptoms did not differ between subjects with and without uncomplicated gastritis or duodenitis. In conclusion, half of this adult population had gastritis strongly associated with H. pylori infection. Gastritis without H. pylori infection was frequently associated with regular NSAID intake. One third had duodenitis, which was associated with H. pylori infection as well as with regular use of NSAIDs and previous cholecystectomy. Digestive symptoms were not overrepresented in uncomplicated gastritis or duodenitis.

The study aimed at investigating the intestinal barrier in Crohn's disease, with special reference to epithelial responses to luminal stimuli, and to permeation of proteins.

Ileal mucosa from patients undergoing intestinal resection was studied in vitro in Ussing chambers. Intestinal permeability was also studied in vivo, by oral load of lactulose and mannitol.

The Ussing chamber was evaluated for intestinal barrier studies. Normal ileal mucosa from patients with colon cancer was subjected to long-term experiments, and investigated in regard to various viability parameters. Mucosal permeability, structural integrity and metabolism were maintained for 90 minutes, and specimens with poor viability were detected by a low transepithelial potential difference. In rat ileal mucosa, luminal sodium caprate, a constituent of milk fat, induced dilatation of the tight junctions as visualised by electron microscopy, and a reversible increase in tight junction permeability. The findings indicate that the Ussing chamber is suitable for studies of the intestinal barrier, including tight junction regulation, provided that experiments are monitored by measurements of transepithelial potential difference and are limited in time.

In vitro studies of human ileal mucosa showed that luminal sodium caprate caused uncoupling of oxidative phosphorylation, as shown by a fall in epithelial ATP contents, and mitochondrial swelling seen by electron microscopy, paralleled by an increased permeability. Non-inflamed Crohn's disease specimens had an exaggerated permeability increase and an augmented fall in transepithelial electrical resistance. Confocal microscopy revealed rearrangements of perijunctional filamentous actin, causing dilatation of the tight junctions. In Crohn's disease, a more pronounced reorganisation of actin filaments was seen, suggesting the tight junctions to be hyperreactive to luminal stimuli due to a disturbed cytoskeletal regulation.

In vivo, an increased intestinal permeability was induced by ingestion of acetylsalicylic acid. One third of both Crohn's disease patients and their first-degree relatives showed an augmented permeability increase, whereas spouses were equal to controls, suggesting a genetically determined vulnerability of the intestinal barrier.

In vitro, non-inflamed ileum from Crohn's disease patients had an increased permeation of ovalbumin. Confocal microscopy suggested this to be caused by an augmented transcytosis, a previously unrecognised defect in the epithelial barrier in Crohn's disease, with a subsequent exposure of antigenic proteins to the subepithelial immunocytes.

The Crohn's disease patients without residual inflammation after surgery were followed with endoscopy within twelve months, and all revealed recurrent ileal inflammation.

The study indicates a perturbed intestinal barrier in Crohn's disease, possibly genetically determined. The impaired barrier function is demonstrated both by an augmented epithelial transcytosis and by hyperreactive tight junctions. The epithelial barrier dysfunction precedes the recurrent intestinal inflammation in ileal Crohn's disease. The findings suggest an interplay between an impaired epithelial barrier and luminal factors in the initiation of intestinal inflammation.

Objective.-To relate the echocardiographic aortic arch-diameter to ambulatory and clinic blood pressure (BP) in patients with aortic coarctation. Design.-Eighteen adult patients (50% men) were recruited from the coarctation registry of the Linkoping Heart Centre. Biplane-trans-oesophageal echocardiography (TEE) was performed with Acuson XP 128/10, ambulatory BP was recorded with Spacelab models 90202/90205. Results.-Systolic clinic and ambulatory BP levels were higher in patients than in the 36 controls (clinic BP: 146 ▒ 25 mmHg vs 119 ▒ 10 mmHg, p = 0.0009, ambulatory BP: 140 ▒ 18 mmHg vs 124 ▒ 11 mmHg, p = 0.009). The differences in diastolic BP levels were less obvious (clinic BP: 87 ▒ 16 mmHg vs 76 ▒ 8 mmHg, p = 0.02, ambulatory BP: 84 ▒ 13 mmHg vs 77 ▒ 9 mmHg, p = 0.052). Daytime ambulatory BP was more strongly related than clinic BP to the coarctation diameter (AD) (systolic BP r = -0.73, p = 0.0006 and r = -0.61, p = 0.007, respectively). In surgically corrected patients (n = 14) only the correlations between ambulatory systolic daytime (r = -0.61, p = 0.02) and night-time (r = -0.58, p = 0.03) BP to AD was statistically significant. Conclusion.-Ambulatory BP correlates strongly with aortic coarctation measured by TEE and would thus be the preferred technique for evaluating BP in this patient category.

Background: Laparoscopic appendectomy (LA) has been associated with a faster recovery and less postoperative pain than the open technique. However, few data are available on the clinical outcome of LA in overweight patients. Methods: A group of 106 patients with a body mass index (BMI) > 26.4, representing the upper quintile of 500 prospectively randomized patients, were included in the study. They were randomized to undergo either laparoscopic or open appendectomy (OA). Operating and anesthesia times, postoperative pain, complications, hospital stay, functional index (1 week postoperatively), sick leave, and time to full recovery were documented. Results: In OA, the operating time for overweight patients was significantly longer than that for patients in the normal weight range (40 vs 35 min, p < 0.05). In LA, there was no difference in operating time between the normal and overweight patients. Overweight patients who underwent LA had longer operating and anesthesia times than their OA counterparts (55 vs 40 min, p < 0.001, and 125 vs 100 min, p < 0.001, respectively). Postoperative pain was significantly greater in overweight patients who underwent OA than in those treated with the laparoscopic technique. Postoperative pain was also significantly greater in overweight patients subjected to OA than in patients of normal weight after 4 weeks, the clinical significance may, however, be of less importance since the values are low (0.26 vs 0.09, p < 0.05). There were no significant differences between the two operating techniques in terms of complications. Hospital stay was longer for overweight patients than for normal-weight patients undergoing OA (3.0 vs 2.0, p < 0.01). The functional index did not differ between any group of patients. Sick leave was longer for overweight patients who underwent OA than for normal-weight patients treated with the same technique (17 vs 13 days, p < 0.01). In the laparoscopic group, however, there were no differences between the overweight and normal-weight patients. Time to full recovery was greater in overweight patients subjected to OA than in the overweight patients in the LA group (22 vs 15 days, p < 0.001). Conclusion: In this study, overweight patients who were submitted to LA had less postoperative pain and a faster postoperative recovery than overweight patients who had OA. LA also abolished some of the negative effects that overweight had on operating time, hospital stay, and sick leave with the open technique. However, anesthesia and operating times were significantly longer in LA for both overweight patients and those with a normal BMI.

No abstract is available for this article.

The outcome of antireflux surgery in a single institution during two decades is presented.

101 consecutive patients operated with open partial2 70° fundoplication and crural repair during 1982-1989 were prospectively analysed. All stages ofpreoperative oesophagitis were represented. Reflux competence, symptomatology, and postoperative side-effects were evaluated six months and ten years postoperatively. Recurrence (8%) was more common in patients who had severe oesophagitis before operation. The operative method is effective for long-term reflux control, it does not cause dysphagia, and it has few side-effect. Some months prior to the introduction oflaparoscopic fundoplication our unit had changed from partial to total fundoplication as a standard operation for gastro-oesophageal reflux disease (GORD). It was then convenient to perform the total Nissen fundoplication laparoscopically. All 50 patients operated with laparoscopic technique during a 30-months period 1992-1994 were prospectively compared with 21 patients operated with open technique. Nine patients were converted and then analysed in the open group. We tried to select patients with uncomplicated disease for laparoscopy but 7 patients in this group had severe disease diagnosed at preoperative endoscopy or/and at operation. In the open group 9 patients had severe disease. The patients were investigated six months, two years, and five years postoperatively. Early postoperative manometry was prognostic for recurrence. At long term follow-up the reflux control was similar, 10% of the patients operated with laparoscopy had recurrence and 8% of the patients operated with open technique.

Summer 1994 to spring 1998 we included 93 patients with uncomplicated GORD in a randomised clinical trial between laparoscopic and open 360° floppy Nissen fundoplication with crural repair. 45 patients were operated on laparoscopically and 48 patients underwent laparotomy. Only one patient was converted and then analysed in the laparotomy group. The patients were investigated before operation, half a year after and at long-term follow-up (33-79 months postoperatively). Long-term follow up also included endoscopy. Operation time was significantly longer for laparoscopy compared to laparotomy, 155.6 (±36.5) minutes and 104.3 (±30.7) minutes respectively (p<0.05). Laparoscopy patients had significantly shorter hospital stay, 3.6 (±1.9) days, compared to 5.8 (±1. 7) days for laparotomy patients. Sick leaves were 20.7 (±9.9) days for laparoscopy patients and 28.3 (14.7) for laparotomy patients. The difference was significant (p<0.05). Early postoperative reflux control was similar for laparoscopic and conventional fundoplication. Early side-effects were more frequent after laparoscopy. Significantly less laparoscopy patients were satisfied at long-term follow-up; only 62% of the laparoscopy patients were satisfied compared to 91% of the laparotomy patients.

We have investigated the mechanisms and anatomical failures in twenty-one patients reoperated after laparoscopic total fundoplication. Recurrent heartburn occurs when wrong part of the stomach is used for the fundoplication. Dysphagia after failed laparoscopic total fundoplication is caused by hiatal fibrosis or other mechanical causes rather than a normal and tight fundoplication.

Also the reproducibility of an important diagnostic tool for GORD, the 24-hour pH monitoring, was evaluated. Twenty-two adult patients admitted to The Oesophageal Laboratory for 24-hour pH monitoring were investigated twice, six weeks apart, under identical conditions. The test was strictly standardised with the use of an antimony pH- probe and the patients hospitalised during 24 hours. We found that a normal 24-hour pH test should be assessed with caution because the biological variability of gastro-oesophageal reflux is not negligible from time to time.

OBJECTIVE:

To investigate the relationship between five-year control of reflux and early postoperative oesophageal function after total fundoplication done either laparoscopically or through a laparotomy in severe and mild reflux disease.

DESIGN:

Prospective open study.

SETTING:

University hospital, Sweden.

PATIENTS:

In the group with severe disease 9 patients had a laparotomy and 7 laparoscopy. The corresponding figures for the group with mild disease were 21 and 34 respectively.

RESULTS:

The increase in lower oesophageal sphincter pressure 6 months after operation in patients with recurrent disease was significantly less than that for patients with good reflux control (p < 0.01). In patients who had laparotomy, including 30% (9/30) with severe reflux disease, good long-term reflux control was found in 93% (27/29). In patients operated on laparoscopically including 17% (7/41) with severe reflux disease good long-term reflux control was found in 90% (35/39).

CONCLUSION:

The mechanism of recurrence differed between patients with severe disease who had a laparotomy and patients with mild disease operated on laparoscopically. Early postoperative manometry was prognostic for recurrence. Long-term reflux control seems to be similar after laparotomy and laparoscopy. Further randomised studies are needed.

Background: The study started in 1994 after over 50 laparoscopic 360^o fundoplications had been performed by the surgeons involved. Complete mobilization of the fundus with posterior crural repair was used where a short floppy total fundoplication was constructed using three non-absorbable sutures, two of them including the esophageal wall. Initial experience in the first 50 consecutive patients operated laparoscopically in this center demonstrated 90% good reflux control.

Methods: Adult patients with uncomplicated reflux disease during the years 1994-1998 were included in this prospective ranomized clincal trial between laparoscopic and open total fundoplication. Patients with long segment Barrett's esophagus, strictures, unhealed severe esophagitis or paraesophageal hernia were excluded, as were patients with previous esophagus or stomach operations, those with weak peristalsis or suspected short esophagus. Two senior surgeons well trained in laparoscopic antireflux surgery performed the 45 laparoscopic operations. Forty-eight patients underwent open surgery performed and supervised by two other senior surgeons well trained in gastroesophageal surgery. One of the latter recruited all patients. Manometry and 24-h esophageal pH monitoring were performed before operation and half a year postoperatively. Manometry also included a short-term reflux test, an acid clearing test and an acid perfusion test. Symptom evaluation (modified DeMeester score) was performed before operation, half a year after and at long-term follow-up (33-79 months postoperatively). Long-term follow-up also included endoscopy.

Results: Half a year after laparoscopy four patients had disabling dysphagia. No patient had disabling dysphagia after laparotomy. Four patients had mild heartburn six mouths after laparoscopy and two patients after laparotomy. Between six months follow-up and long-term follow up six patients were reoperated in the laparoscopy group and two patients in the laparotomy group. Three patients operated with laparotomy had died in intercurrent diseases. After laparoscopy, at long-term follow-up, 62% (28/45) were satisfied compared to 91% ( 41145) after laparotomy. The difference was significant (p<0.01).

Conclusions: Early postoperative reflux control was similar for laparoscopic and conventional fundoplication. At long-term follow-up significantly more patients were satisfied after laparotomy than after laparoscopy.

Background:

This was a prospective study of symptoms, and short-term and long-term reflux competence after partial fundoplication.

Methods:

Some 101 patients were operated consecutively with posterior partial (270°) fundoplication. Indications for surgery were reflux disease without erosive oesophagitis in 25 patients, moderate oesophagitis in 43, severe oesophagitis in 25 and paraoesophageal hernia in eight. Symptom score, manometry and pH tests were performed before operation, 6 months after operation and after 6–14 years.

Results:

All patients (n = 101) were free from heartburn and regurgitation at early follow-up. There was evidence of clinical recurrence at late follow-up (n = 87) in two of 22 patients without oesophagitis before operation, two of 39 with moderate oesophagitis before operation and three of 19 patients with severe oesophagitis before operation; 92 per cent had good reflux control at late follow-up.

Conclusion

Posterior partial fundoplication shows excellent reflux control at early follow-up. Ten years later fewer than 10 per cent of patients have recurrence, which is more common in patients who had severe oesophagitis before operation.

OBJECTIVE:

To investigate the mechanisms and anatomical failures after total laparoscopic fundoplication using the symptoms and findings at reoperation.

DESIGN:

Prospective open study.

SETTING:

University hospital, Sweden.

PATIENTS:

Twenty-one patients who were reoperated on a median of 33 (0.5-102) months after laparoscopic fundoplication.

INTERVENTIONS:

The patients were divided into three groups according to the mode of presentation. The first group presented with dysphagia and no gastro-oesophageal reflux (GOR) (n = 6). The second group (n = 11) had recurrent GOR and the third group (n = 4) complained of a sense of excessive fullness.

RESULTS:

In the dysphagia group the reason for it in 4 patients was severe fibrosis in the hiatal region including the right part of the fundoplication. One patient had correctly located fundoplication but it was too tight. In the last patient the part of the stomach used was too low down. All patients in the GOR group had a slippage and rupture of the fundoplication. Ten patients also had a recurrent hernia. In 6/11 patients the fundal mobilisation was incomplete. In the last group (excessive fullness) one patient had a postoperative leak from the fundal part, one patient a para-oesophageal hernia, and one patient an intact but herniated repair. One further patient had an intact abdominal oesophagus and crural repair, but a large portion of the stomach had herniated through the left part of the fundoplication and acted as a volvulus.

CONCLUSIONS:

Dysphagia was caused by hiatal fibrosis or other technical failures rather than a normal tight fundoplication. Using the wrong part of the stomach causes recurrent heartburn. The laparoscopic suturing technique must be improved.

BACKGROUND:

Twenty-four-hour pH monitoring is an investigation technique that can give both false-positive and false-negative results, depending on patient factors such as diet and different activities. The aim was to study the reproducibility of 24-h oesophageal pH monitoring under as standardized conditions as possible in patients with symptoms of gastro-oesophageal reflux disease.

METHODS:

Antimony pH electrodes were used in 22 adult patients who were investigated twice, 6 weeks apart, under identical conditions. They were hospitalized and were served a standardized diet which had been tested to contain no lower than pH 5.0. Neither coffee nor smoking was allowed. The patients had to refrain from proton-pump inhibitors for 10 days and H2 blockers for 2 days prior to the investigation. The paired t test was used.

RESULTS:

There was no significant difference in total reflux time, upright or supine reflux time, or longest reflux periods between the two test occasions. However, there were discordant results in six patients who had normal total reflux time on one test occasion but pathological results on the other.

CONCLUSION:

Since the biological variability of gastro-oesophageal reflux is not negligible from time to time, a normal 24-h oesophageal pH test should be assessed with caution.

In a population-based cohort of 4694 women with invasive breast cancer, operated upon with breast conserving surgery (BCS) in 1981-1990 and followed through to 1997, we studied how this technique had been adopted into clinical practice, especially with reference to the use of radiotherapy (RT). Our main aim was to see whether there was a drift in the risk of local recurrence and breast cancer death over time. During the 30 151 person-years of observation in the cohort, there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to other causes. Postoperative RT was given to 70.2%, but usage increased over the period. The women not receiving RT were mostly elderly, but also in women <70 years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6 and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local recurrence at 10 years. Thus, the choice not to irradiate failed to target women at a low risk. In a multivariate Cox analysis taking tumour size, nodal status, age at operation and RT into account, there was a trend for a higher risk of local recurrence in the later time period, relative hazard 1.5 (95% confidence interval (CI) 1.0-2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years, respectively. ⌐ 2001 Elsevier Science Ltd. All rights reserved.

Background: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. Methods: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. Results: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. Conclusion: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.

In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (=2 years) recurrence in the same quadrant as the primary tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and 56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in the probability of breast cancer-specific survival, as measured from the recurrence, between women who initially did or did not receive radiotherapy (P=0.0123). However, when measured from primary treatment, there was no significant difference, indicating that the difference in prognosis could be due to a lead-time bias. Independent prognostic factors for breast cancer-specific survival in women with local recurrences were time to local recurrence and the Nottingham Prognostic Index (NPI). ⌐ 2002 Elsevier Science Ltd. All rights reserved.

Background: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. Method: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. Results: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. Conclusion: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.

The gastrointestinal hormone cholecystokinin (CCK) is known to be oneof the most potent stimulators of pancreatic growth. CCK is alsosuggested to be an initiator and/or promotor of pancreatic carcinogenesis. This study was undertaken to elucidate the effects oflong-term stimulation with exogenous and endogenous CCK andexogenous secretin on exocrtne and endocrine pancreatic cell proliferation (in rats and mice) and on . endocrine (B-cell) function (inrats). Cell kinetics were studied autoradiographically by means of 3H-thymidine labeling of DNA synthesizing cells and endogenous increasein plasma CCK level was induced by surgical pancreatico-biliary diversion (PBD).

The study showed that long-term stimulation with the CCK analogue cerulein (in mice) as well as endogenously induced hyperCCKemia (in rats) induced pancreatic hyperplasia. The proliferative response was as high, or even higher, in the ductal and centroacinar cell populations than in the acinar one, which traditionally is regarded as the target forCCK. The cells adapt to the continuous CCK stimulation with a decrease in proliferative activity to control level after 14-20 days. Cerulein seems to induce early changes in the centroacinar cell region with signs of transition of cells from acinar to centroacinar position. Secretin, which has the ductal cells as its main target cell, had no growth stimulating effect on any of the studied cell types. Long-term endogenous CCK stimulation does not affect the proliferation of cells in the islands of Langerhans, nor affect the insulin secretory response or the glucose elimination following intravenous glucose loading. The results of the study are of special interest as human pancreatic carcinoma is considered to be ductal and as there are suggestions of early changes in the centroacinar · region in experimental pancreatic carcinogenesis. Funhermore, the PBD model was found to be suitable for studies on longterm CCK effects, as the pancreatic growth response following PBD was exclusively caused by the increased plasma CCK level.

Estrogens play a crucial role in the development of breast cancer. Estradiol can be produced in the breast tissue in situ, and one of the enzymes involved in this process is 17β-hydroxysteriod dehydrogenase (17β-HSD) type 1 that catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17β-HSD type 1 (HSD17B1) is located at 17q12-21, close to the more studied ERBB2 and BRCA1. The aim of this study was to investigate if HSD17B1 shows an altered gene copy number in breast cancer. We used real-time PCR and examined 221 postmenopausal breast tumors for amplification of HSD17B1 and ERBB2. In all, 32 tumors (14.5%) showed amplification of HSD17B1 and 21% were amplified for ERBB2. Amplification of the two genes was correlated (P = 0.00078) and in 14 tumors (44%) with amplification of HSD17B1, ERBB2 was co amplified. The patients with amplification in at least one of the genes had a significantly worse outcome than patients without (P = 0.0059). For estrogen receptor (ER)-positive patients who received adjuvant tamoxifen, amplification of HSD17B1 was related to decreased breast cancer survival (P = 0.017), whereas amplification of ERRB2 was not. Amplification of HSD17B1 might be an indicator of adverse prognosis among ER-positive patients, and possibly a mechanism for decreased benefit from tamoxifen treatment.

Background: To assess the effects of treatment with nebulized corticosteroids immediately after chlorine gas injury. Methods: Eighteen anesthetized and mechanically ventilated pigs were exposed to chlorine gas (140 ppm for 10 minutes) and observed for 6 hours. Nine pigs were treated with nebulized beclomethasone-dipropionate 20 ╡g/kg (BDP group), and nine pigs were given no treatment (control group). Results: All animals developed severe pulmonary dysfunction. The initial decrease in PaO2 was similar in both groups, but BDP-treated animals improved whereas control animals deteriorated (p < 0.005, analysis of variance). Pulmonary vascular resistance increased in both groups but less in the BDP group (p < 0.01). Lung-thorax compliance was better preserved in the BDP group (p < 0.01), and oxygen delivery was significantly better in the BDP group (p < 0.01). One animal died in the BDP group, as did three animals in the control group. Conclusion: Immediate treatment with nebulized BDP improved pulmonary and cardiovascular function after experimental chlorine gas injury.

Objective: To analyze reoperation rates for recurrent and primary groin hernia repair documented in the Swedish Hernia Register from 1996 to 1998, and to study variables associated with increased or decreased relative risks for reoperation after recurrent hernia.

Methods: Data were retrieved for all groin hernia repairs prospectively recorded in the Swedish Hernia register from 1996 to 1998. Actuarial analysis adjusted for patients' death was used for calculating the cumulative incidence of reoperation. Relative risk for reoperation was estimated using the Cox proportional hazards model.

Results: From 1996 to 1998, 17,985 groin hernia operations were recorded in the Swedish Hernia Register, 15% for recurrent hernia and 85% for primary hernia. At 24 months the risk for having had a reoperation was 4.6% after recurrent hernia repair and 1.7% after primary hernia repair. The relative risk for reoperation was significantly lower for laparoscopic methods and for anterior tension-free repair than for other techniques. Postoperative complications and direct hernia were associated with an increased relative risk for reoperation. Day-case surgery and local infiltration anesthesia were used less frequently for recurrent hernia than for primary hernia.

Conclusions: Recurrent groin hernia still constitutes a significant quantitative problem for the surgical community. This study supports the use of mesh by laparoscopy or anterior tension-free repair for recurrent hernia operations.