<p>Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. </p><p>Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.</p><p>Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.</p><p>A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.</p><p>Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.</p>

<p>The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma.</p><p> In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties.</p><p> In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer.</p><p> The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively.</p><p> New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis.</p><p> Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.</p>

<p>Oral 111-Indium-DTPA colonic scintigraphy was used to assess segmental transit in 23 patients with slow transit constipation (STC) and 13 controls. The transit time did not differ between patients and controls in the right colon, whereas the patients had a consistent delay from the transverse colon and distally (<i>P</i><0.05–0.001). Two individual patients had a delay in the right colon.</p><p>Twenty-eight patients underwent a left- (n=26) or a right (n=2) hemicolectomy for STC, after evaluation including colonic scintigraphy. Twenty-three patients (80%) were satisfied with the outcome after a median of 50 months. The median stool frequency increased from one to seven per week (<i>P</i><0.001). The number of patients with bloating, excessive straining and painful defecation decreased (<i>P</i><0.05). The laxative use decreased (<i>P</i><0.01) and faecal continence was unchanged. A blunted rectal sensation correlated to a poor outcome.</p><p>Fifty constipated patients with slow colonic transit and 28 controls were investigated with anorectal manovolumetry. Anal resting pressure was lower (<i>P</i><0.05), and squeeze pressure tended to be lower (<i>P</i>=0.09) in patients. Rectal sensation was not different between groups, although ten patients had a threshold for filling sensation above the 95^th percentile of controls. The rectal compliance was increased in patients (<i>P</i><0.05–0.01).</p><p>Total and segmental colonic transit was assessed with radio-opaque marker study and scintigraphy in 35 constipated patients, and related to normal values. Twenty-seven of 31 female patients had a prolonged total transit time on marker study, and 26 on scintigraphy. Of those 31 patients, 29 had prolonged segmental transit only in one or two segments on marker study. The two methods gave a similar result, except in the descending colon (<i>P</i><0.05). However, the results varied considerably for individual patients.</p><p>In conclusion, patients with STC often benefit from a segmental colonic resection, following assessment including scintigraphy. Anorectal physiology testing may predict surgical results.</p>

<p>One of the main obstacles to maintaining patients with short bowel syndrome on parenteral nutrition, or successfully transplanting these patients with a small bowel graft, is the many severe infections that occur. Evidence is accumulating that translocating bacteria from the patient’s bowel causes a significant part of these infections. In this thesis bacterial translocation is studied in a Thiry-Vella loop of defunctionalised small bowel in the rat. </p><p>Bacterial translocation to the mesenteric lymph nodes (MLNs) occurs in almost 100% of the rats after three days. No systemic spread of bacteria is observed unless there is additional immunosupression with depletion of Kupffer cells in the liver. However, blocking the function of α/β T cells does not increase the translocation. Removal of MLNs does not either aggravate bacterial translocation in the Thiry-Vella loop model. Conversely, after small bowel transplantation translocating bacteria spread systemically if the MLNs are removed. </p><p>The Thiry-Vella loop should also be a suitable model for the testing of potentially translocation-inhibiting substances. Reinforcement of the intestinal barrier with glutamine or phosphatidylcholine proved insufficient in decreasing bacterial translocation. Even selective bowel decontamination with tobramycin failed to abolish bacterial translocation. Thus, it seems that the driving force for translocation in this model is strong regardless of the relatively small trauma of intestinal defunctionalisation.</p><p>Flow cytometric studies of the immune cells in the spleen MLNs showed a decrease in MHC class II positive T cells in the MLNs of the Thiry-Vella loop. Concurrently the number of macrophages increased with time as observed by immunohistochemistry. The fraction of MHC class II negative macrophages increased in the spleens of rats treated with glutamine. </p><p>In conclusion, the Thiry-Vella loop model offers possibilities of immunological as well as mechanistic studies on bacterial translocation from small intestine.</p>

<p>In a prospective randomised double-blind study eighty patients with MRI verified lumbar disc herniation and corresponding clinical findings underwent microscopic disc removal. The patients were peroperatively given systemic and local corticosteroids or placebo, and followed for 2 years. The hospital stay and time to return to full-time work was significantly shorter in the treatment group. Pain measured as worst pain during the last week was also lower in the corticosteroid group. The results indicate that peroperative treatment with corticosteroids reduces pain and improves the functional outcome in patients operated for lumbar disc herniations.</p><p>To evaluate whether thermal quantitative sensory testing (QST) is applicable in the study of sensory dysfunction in lumbar disc herniations 66 patients with disc herniations underwent thermal QST. We found that thermal QST reflects sensory dysfunction in patients with lumbar disc herniations. However, thermal QST seems to have a poor predictive value for identifying the anatomic location of a herniated lumbar disc.</p><p>Quantitative sensory testing (QST) was used to detect damage to the myelinated A-delta fibres (cold sense) and the unmyelinated C-fibres (warmth sense). Corticosteroids combined with surgery in lumbar disc surgery improved the normalisation for the warmth disturbance compared to the control group. </p><p>A prospective analysis was performed on the predictive value of preoperatively determined lumbar lordosis and flexion for pain and disability in patients treated by microscopic lumbar disc surgery. Preoperative hyperlordosis correlated to more pain postoperatively (p=0.004). In patients with hypoflexion there was an association between hyperlordosis and moderate or severe pain postoperatively (p<0.001). The same outcomes were found for DRI. The stiff and straight back indicates a good outcome of lumbar disc surgery concerning pain and disability. </p>

The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma. In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties. In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer. The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively. New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis. Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.

The aim was to study pathophysiological mechanisms and risk factors for developing atrial fibrillation (AF) after coronary artery bypass grafting (CABG), and the effect of thoracic epidural anaesthesia (TEA). The study comprised 141 patients undergoing CABG, including 45 patients randomised for TEA intra- and postoperatively. All patients underwent 24-hour Holter monitoring pre- and postoperatively for the analysis of arrhythmias and heart rate variability (HRV). Catecholamines and neuropeptides (reflecting sympathetic and parasympathetic activity), atrial peptides and echocardiographically assessed atrial arias were obtained pre- and postoperatively. Logistic regression analysis identified body mass index (BMI), maximum supraventricular beats (SPB) per minute, and total amount of cardioplegia as independent predictors of postoperative AF. Patients developing AF showed limited diurnal variation of HRV preoperatively. All HRV parameters decreased significantly in all patients postoperatively. The significant postoperative increase in atrial areas and atrial peptides did not differ between patients developing AF and those who did not. TEA had no effect on the incidence of postoperative AF, but resulted in lower heart rate, less increase in adrenaline levels, and decreased neuropeptide levels (reflecting sympathetic and parasympathetic activity). AF was initiated by an SPB in 72.4% of non-TEA and 100% of TEA treated patients, whereas changes in heart rate only, before onset, were seen in 17.2% non-TEA patients. The observed risk factors, SPB and cardioplegia, may both induce electrophysiological changes known to increase the susceptibility to AF. The observed postoperative atrial dilatation and autonomic imbalance, indicated by HRV and neuropeptide levels, may further favour the development of AF. The observation that a majority of postoperative AF was initiated by a premature atrial contraction supports our hypothesis that latent atrial foci may be a major trigger mechanism of postoperative AF.

Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough. The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN. In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function. Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches. In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.

Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease. Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor. A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions. Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.

Oral 111-Indium-DTPA colonic scintigraphy was used to assess segmental transit in 23 patients with slow transit constipation (STC) and 13 controls. The transit time did not differ between patients and controls in the right colon, whereas the patients had a consistent delay from the transverse colon and distally (P&lt;0.05–0.001). Two individual patients had a delay in the right colon. Twenty-eight patients underwent a left- (n=26) or a right (n=2) hemicolectomy for STC, after evaluation including colonic scintigraphy. Twenty-three patients (80%) were satisfied with the outcome after a median of 50 months. The median stool frequency increased from one to seven per week (P&lt;0.001). The number of patients with bloating, excessive straining and painful defecation decreased (P&lt;0.05). The laxative use decreased (P&lt;0.01) and faecal continence was unchanged. A blunted rectal sensation correlated to a poor outcome. Fifty constipated patients with slow colonic transit and 28 controls were investigated with anorectal manovolumetry. Anal resting pressure was lower (P&lt;0.05), and squeeze pressure tended to be lower (P=0.09) in patients. Rectal sensation was not different between groups, although ten patients had a threshold for filling sensation above the 95th percentile of controls. The rectal compliance was increased in patients (P&lt;0.05–0.01). Total and segmental colonic transit was assessed with radio-opaque marker study and scintigraphy in 35 constipated patients, and related to normal values. Twenty-seven of 31 female patients had a prolonged total transit time on marker study, and 26 on scintigraphy. Of those 31 patients, 29 had prolonged segmental transit only in one or two segments on marker study. The two methods gave a similar result, except in the descending colon (P&lt;0.05). However, the results varied considerably for individual patients. In conclusion, patients with STC often benefit from a segmental colonic resection, following assessment including scintigraphy. Anorectal physiology testing may predict surgical results.