Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer. © 2007 Taylor & Francis.
OBJECTIVE: A systematic review of the nonsurgical treatment of patients with appendiceal abscess or phlegmon, with emphasis on the success rate, need for drainage of abscesses, risk of undetected serious disease, and need for interval appendectomy to prevent recurrence. SUMMARY BACKGROUND DATA: Patients with appendiceal abscess or phlegmon are traditionally managed by nonsurgical treatment and interval appendectomy. This practice is controversial with proponents of immediate surgery and others questioning the need for interval appendectomy. METHODS: A Medline search identified 61 studies published between January 1964 and December 2005 reporting on the results of nonsurgical treatment of appendiceal abscess or phlegmon. The results were pooled taking the potential clustering on the study-level into account. A meta-analysis of the morbidity after immediate surgery compared with that after nonsurgical treatment was performed. RESULTS: Appendiceal abscess or phlegmon is found in 3.8% (95% confidence interval (CI), 2.6-4.9) of patients with appendicitis. Nonsurgical treatment fails in 7.2% (CI: 4.0-10.5). The need for drainage of an abscess is 19.7% (CI: 11.0-28.3). Immediate surgery is associated with a higher morbidity compared with nonsurgical treatment (odds ratio, 3.3, CI: 1.9-5.6, P < 0.001). After successful nonsurgical treatment, a malignant disease is detected in 1.2% (CI: 0.6-1.7) and an important benign disease in 0.7% (CI: 0.2-11.9) during follow-up. The risk of recurrence is 7.4% (CI: 3.7-11.1). CONCLUSIONS: The results of this review of mainly retrospective studies support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon. © 2007 Lippincott Williams & Wilkins, Inc.
Objective: To report prognostic factors and follow-up data for an unselected group of patients with carcinoma in situ (CIS) of the urinary bladder treated with bacille Calmette-Guérin (BCG). Material and Methods: The clinical records of patients with CIS treated with BCG were reviewed. All 173 patients treated between 1986 and 1997 in four hospitals in two Swedish cities were included. The median follow-up period was 72 months (range 6-154 months). The impact of 18 variables on the times to recurrence and progression was studied using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. Results: No pre-treatment variables, including type of CIS and T1G3 tumour, had prognostic value in terms of time to progression. The result of the first cystoscopy had a very strong prognostic importance: 44% of patients with a positive first cystoscopy progressed in stage, 59% were BCG failures and 35% died from urothelial cancer. The corresponding values for patients with a negative first cystoscopy were 11%, 18% and 8%. Fourteen patients (8%) were diagnosed with an upper urinary tract tumour but no variable had prognostic significance. The diagnoses of the upper urinary tract tumours were evenly distributed during follow-up. Conclusions: We were not able to predict which patients would respond favourably to BCG. Cystectomy should be strongly considered even after a positive first cystoscopy. The accumulated incidence of patients with bladder CIS and a subsequent upper urinary tract tumour is rather high but it is questionable whether the prognosis will improve if routine follow-up urographies are performed.
Background and aim: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. Patients and methods: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. Results: A total of 281 patients were enrolled and randomised, 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p = 0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p = 0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. Conclusion: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.
[No abstract available]
Objective: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. Background: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. Methods: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. Results: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. Conclusion: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids. Copyright © 2005 by Lippincott Williams & Wilkins.
Objectives: To examine the risk of developing adrenal carcinomas and clinically overt hypersecreting tumours during short-term follow-up in patients with adrenal incidentalomas. Design: 229 (98 males and 131 females) patients with adrenal incidentalomas were investigated in a prospective follow-up study (median time 25 months, range 3-108 months). The patients were registered between January 1996 and July 2001 and followed until December 2004. Twenty-seven Swedish hospitals contributed with follow-up results. Methods: Diagnostic procedures were undertaken according to a protocol including reinvestigation with computed tomography scans after 3-6 months, 15-18 months and 27-30 months, as well as hormonal evaluation at baseline and after 27-30 months of follow-up. Operation was recommended when the incidentaloma size increased or if there was a suspicion of a hypersecreting tumour. Results: The median age at diagnosis of the 229 patients included in the follow-up study was 64 years (range 28-84 years) and the median size of the adrenal incidentalomas when discovered was 2.5 cm (range 1-8 cm). During the follow-up period, an increase in incidentaloma size of ≥0.5 cm was reported in 17 (7.4%) and of ≥ 1.0 cm was reported in 12 (5.2%) of the 229 patients. A decrease in size was seen in 12 patients (5.2%). A hypersecreting tumour was found in 2% of the hormonally investigated patients: cushing's syndrome (n = 2) and phaeochromocytoma (n = 1). Eleven patients underwent adrenalectomy, but no cases of primary adrenal malignancy were observed. Conclusions: Patients with adrenal incidentaloma had a low risk of developing malignancy or hormonal hypersecretion during a short-term follow-up period. © 2006 Society of the European Journal of Endocrinology.
Background: Iatrogenic nerve injury caused by heat from dissection instruments is a significant problem in many areas of surgery. The aim of the present study was to compare the risk of nerve injury for three different dissection instruments: monopolar and bipolar electrosurgery (ES) and an ultrasonically activated (US) instrument. Methods: The biceps femoris muscle was cut in a standard manner just adjacent to the sciatic nerve using monopolar ES, bipolar ES or US shears. A total of 73 functional experiments were conducted in which the nerve was isolated, divided proximally, and stimulated supramaximally in 37 anaesthetized rats. The electromyographic (EMG) potential was recorded distally before and after each experiment. Nerve dysfunction was defined as more than 10 per cent loss of the evoked EMG potential. Fifty-nine nerves were examined histologically after dissection with the different instruments. The extent of heat damage was determined in four nerves that were divided with ES bipolar scissors and five that were divided with US shears. Results: Reduction in the EMG potential was significantly more frequent in the monopolar ES group than in the US group. Morphological examination also showed significantly less nerve damage in the US group. Conclusion: US instruments may be safer than ES for dissection close to nerves. Copyright © 2005 British Journal of Surgery Society Ltd.
Background. Following a motorcycle accident, a 9-year-old boy experienced a complete right-sided ( dominant) arm and hand paralysis with total sensory loss, Horner syndrome and severe constant pain. This study assessed the long-term outcome of spinal cord surgery undertaken on the patient, focusing on the restored hand function and related cortical activity. The study follows on from previous reports on the same patient. Investigations. Clinical functional and electrophysiological examinations. Functional MRI of cortical activity. Diagnosis. Complete brachial plexus (C5-T1) avulsion from the spinal cord. Management. Spinal cord surgery to restore motor trajectories.
BACKGROUND. Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I-III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow-up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure. METHODS. Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin-6 (IL-6) production was measured with enzyme-linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months. RESULTS. A production of >5000 pg/mL of IL-6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL-6 died from cancer within the follow-up period, whereas no cancer-related deaths were recorded among 21 patients with 5000 pg/mL IL-6 or less. A multivariate Cox regression analysis, stratified for T- and N-stage, identified IL-6 production as an independent prognostic factor. CONCLUSIONS. IL-6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. © 2007 American Cancer Society.
We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1 046 operated women to postoperative RT or control between 1987 and 1999. The primary endpoint was ipsilateral local recurrence. Secondary endpoints were contralateral breast cancer, distant metastasis and death. After a median follow-up of 5.2 years (range 0.1-13.8) there were 44 recurrences in the RT group corresponding to a cumulative incidence of 0.07 (95% confidence interval (CI) 0.05-0.10). In the control group there were 117 recurrences giving a cumulative incidence of 0.22 (95% CI 0.18-0.26) giving an overall hazard ratio of 0.33 (95% CI 0.24-0.47, p <0.0001). Twenty two percent of the patients had microscopically unknown or involved margins. We found no evidence for different effects of RTon the relative risk of invasive or in situ recurrence. Secondary endpoints did not differ. Women undergoing sector resection for DCIS under conditions of population based screening mammography benefit from postoperative RT to the breast. Seven patients needed RT-treatment to prevent one recurrence. © 2006 Taylor & Francis.
Background: Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations. Patients and methods: We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing. Results: MSI (13% of 438 cases) was not associated with survival (rate ratio=0.97, 95% confidence interval =0.57-1.64, P=0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P=0.01) and negative/weak expression of hMLH1 (P=0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P=0.01), proximal tumour (P=0.01), stage B (P=0.01) and poor differentiation (P=0.047). Conclusions: MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.
Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r = 0.80; RBC concentration: r = 0.94). This correlation increases with longer occlusion durations (1, 5 and 10 min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2) = 0.59; RBC concentration: r(2) = 0.78) and the recovery times (perfusion: r(2) = 0.62; RBC concentration: r(2) = 0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.
Objective: To establish normal ranges for timed micturition, i.e. the time to void the first 100 ml, study its dependency on voided volume and age and compare it to maximum flow rate. Material and Methods: Randomly selected men from the National Register without voiding symptoms were investigated. These 58 men (aged 30-75 years) registered 1286 voidings (median 21 per person) at home with the aid of a portable uroflowmeter. Timed micturition and maximum flow rate were obtained from the same voidings. Results: An increase in timed micturition with an increase in age was confirmed. When estimating normal ranges it was sufficient to use the age groups ≤55 years and ≥56 years. Maximum flow rate is shown in nomograms with voided volume. Timed micturition had less dependency on voided volume than maximum flow rate. The normal ranges of timed micturition are ≤9 s for men aged ≤55 years and ≤15 s for those aged ≥56 years. The true median of timed micturition for men aged ≥56 years may be 6 s lower or 2.5 s higher than the value of a single measurement. Corresponding figures for maximum flow rate are 5 and 6 ml/s. Conclusions: Timed micturition has a low dependency on volume and values of ≤9 s and ≤15 s are normal for men aged ≤55 years and ≥56 years, respectively.
Objective: To compare and evaluate manually performed timed micturition in a domestic setting with registrations made using a home flowmeter. Material and Methods: Forty-six randomly selected men without voiding symptoms performed timed micturition at home both by hand and with a Da CapoTM home flowmeter. Statistical comparison using the Wilcoxon signed-rank test and regression analysis of the differences was performed to evaluate whether the two methods were comparable. Results: In two cases, there was a large discrepancy between the two methods. For the remaining 44 men, there were no statistically significant differences between the two methods. The median (range) timed micturition was 7 s (3-35 s) for manual measurements and 6.5 s (3.5-28 s) for electronic measurements. For each individual, the difference between the manually and electronically obtained medians was calculated. The average individual difference was 0.06 s (SD 1.6 s). Conclusion: Approximately 95% of men are able to measure timed micturition at home manually without statistically or clinically significant differences from electronically obtained measurements. One has to be aware that in a small proportion of cases timed micturition measured at home may be falsely long.
Object. The authors conducted a study to determine age- and time-dependent effects on the functional outcome after median nerve injury and repair and how such effects are related to changes in the pattern of cortical activation in response to tactile stimulation of the injured hand. Methods. The authors studied 11 patients with complete unilateral median nerve injury at the wrist repaired with epineural suture. In addition, 8 patients who were reported on in a previous study were included in the statistical analysis. In the entire study cohort, the mean age at injury was 23.3 +/- 13.4 years (range 7-57 years) and the time after injury ranged from 1 to 11 years. Sensory perception was measured with the static 2-point discrimination test and monofilaments. Functional MR imaging was conducted during tactile stimulation (brush strokes) of Digits II-III and IV-V of both hands, respectively. Results. Tactile sensation was diminished in the median territory in all patients. The strongest predictor of 2-point discrimination was age at injury (p less than 0.0048), and when this was accounted for in the regression analysis, the other age- and time-dependent predictors had no effect. The activation ratios (injured/healthy hand) for Digit II-III and Digit IV-V stimulation were positively correlated (rho 0.59, p less than 0.011). The activation ratio for Digit II-III stimulation correlated weakly with time after injury (p less than 0.041). The activation ratio of Digits IV-V correlated weakly with both age at injury (p less than 0.048) and time after injury (p less than 0.033), but no predictor reached significance in the regression model. The mean ratio of ipsi- and contralateral hemisphere activation after stimulation of the injured hand was 0.55, which was not significantly different from the corresponding ratio of the healthy hand (0.66). Conclusions. Following a median nerve injury (1-11 years after injury) there may be an initial increase in the volume of the cortical representation, which subsequently declines during the restoration phase. These dynamic changes may involve both median and ulnar nerve cortical representation, because both showed negative correlation with time after injury. These findings are in agreement with animal studies showing that cortical plasticity is an important mechanism for functional recovery after peripheral nerve injury and repair.
Purpose: Interpretation of physical activity as energy expenditure requires adjustment for body size. This is usually accomplished by means of the MET system, which assumes a basal metabolic rate (BMR) of 4.184 kJ·kg -1·h-1 and, when the standard calculation is used, that the energy costs of different activities are proportional to BMR. These relationships may be altered by increases in percent total body fat (% TBF), and this paper examines relationships between % TBF and total energy expenditure (TEE) obtained using the standard and a proposed calculation. Methods: Published data regarding body composition, physical activity (heart rate recording), and BMR in 11 American women (before and after weight gain) and in 15 Swedish women (before and during pregnancy) were used to calculate TEE. Reference estimates of TEE were obtained using doubly labeled water. Results: In Swedish women, reference TEE minus standard TEE (MJ·24 h-1) was 1.37 ± 1.29 (P < 0.01) before and 1.03 ± 1.13 (P < 0.05) during pregnancy. For proposed TEE these differences were 0.43 ± 1.63 (P > 0.05) and 0.31 ± 1.28 (P > 0.05) (MJ·24 h-1), respectively. In American women before and after weight gain, reference TEE minus standard TEE (MJ·24 h-1) were 0.38 ± 1.79 (P > 0.05) and 1.39 ± 2.36 (P > 0.05), respectively, whereas the corresponding differences for proposed TEE (MJ·24 h-1) were -0.52 ± 2.20 (P > 0.05) and 0.21 ± 2.36 (P > 0.05), respectively. In Swedish women before pregnancy and American women after weight gain (N = 26, BMI = 18-39), significant (P < 0.001) relationships were found for standard TEE/proposed TEE (y) versus % TBF, (x, r = -0.65) and versus BMI (x, r = -0.70). Conclusions: In individuals with a TBF content typical for contemporary Western women, standard TEE is lower than proposed TEE. This bias increases as the TBF content of subjects increases. The results indicate that proposed TEE is more accurate than standard TEE, but this requires confirmation. Copyright © 2006 by the American College of Sports Medicine.
Objective. No long-term studies of laparoscopic and open fundoplication were available in 1994. The aim of this study was to compare reflux control and side effects after laparoscopic and open fundoplication. Material and methods. Adult patients with uncomplicated gastro-oesophageal reflux disease were included in this prospective randomized clinical trial between laparoscopic and open 360° fundoplication. Patients with uncomplicated gastro-oesophageal reflux disease were included with the exception of those with weak peristalsis or suspected short oesophagus. Two senior surgeons, well trained in laparoscopic antireflux surgery, performed the 45 laparoscopic operations. Forty-eight patients underwent open surgery performed or supervised by two other senior surgeons, also well trained in gastro-oesophageal surgery. One of the latter recruited all the patients. Manometry and 24-h oesophageal pH monitoring were performed before operation and 6 months postoperatively. Manometry also included a short-term reflux test, an acid clearing test and an acid perfusion test. Symptom evaluation was performed before surgery, 6 moths after and at long-term follow-up (33-79 months postoperatively) by the same surgeon. Long-term follow-up also included endoscopy. Results. Six months after laparoscopy 4 patients had disabling dysphagia. None of the patient had disabling dysphagia after laparotomy. Four patients had mild heartburn 6 months after laparoscopy and 2 patients after laparotomy. Between 6 months' follow-up and long-term follow-up, 6 patients were reoperated on in the laparoscopy group and 2 patients in the laparotomy group. Three patients operated on with laparotomy had died of intercurrent diseases. After laparoscopy, at long-term follow-up, 62% of patients (28/45) were satisfied compared with 91% (41/45) 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. © 2005 Taylor & Francis.
Objective. The inhibitory proteins, IκBs, regulate the activity of nuclear factor kappa-beta (NF-κB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IκBs may be involved in cancer development through the activation of NF-κB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3′ UTR of NFKBIA (encoding IκBα) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients. Material and methods. A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR-restriction fragment length polymorphism. Results. The frequency of the AG genotype was increased in the Chinese patients ≥50 years of age compared with the Chinese controls (odds ratio (OR) = 3.06, 95% confidence interval (CI) = 1.55-6.02, p=0.001), even when adjusted for age (OR = 3.20, 95% CI = 1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl = 1.28-7.60, p=0.01). Conclusions. Chinese individuals ≥50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients. © 2007 Taylor & Francis.
The aim of this study was to identify cell adhesion molecules that could serve as targets of the human follicle-associated epithelium (FAE) overlying Peyer's patches and to assess nanoparticle uptake levels across this epithelium. We first studied the expression of the mouse M-cell marker β1- integrin and used a model of human FAE derived from intestinal epithelial Caco-2 cells and Raji B-cells to identify additional potential targets by cDNA array. The protein expression of potential targets in the model FAE and in human ileal FAE tissues was quantified by immunofluorescence. Integrin targeting was studied by investigating the transport of Arg-Gly-Asp (RGD)-coated (integrin-binding), Arg-Gly-Glu (RGE)-coated (nonintegrin-binding), and uncoated nanoparticles across ileal specimens mounted in Ussing chambers. Both β1- integrin and the cell adhesion molecule CD9 were more abundantly expressed in the model and human FAE compared with the Caco-2 control cells or villus epithelium (VE). Uncoated nanoparticles were not taken up across either FAE or VE. General integrin targeting with RGD improved the nanoparticle transport dramatically across the FAE and to a lower extent across the VE. Compared with RGE, RGD improved transport 4-fold across the FAE. There was no difference in the transport of RGD- and RGE-coated nanoparticles across the VE. In conclusion, β1-integrin and CD9 were identified as targets in human FAE. The difference in RGD- and RGE-mediated transport across the FAE, but not the VE, suggests that a specific integrin interaction was the dominating mechanism for improved nanoparticle uptake across the FAE., whereas charge interaction contributed substantially to the improved VE uptake. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.
Providing cutaneous wounds with sufficient epidermis to prevent infections and fluid loss is one of the most challenging tasks associated with surgical treatment of burns. Recently, application of cultured keratinocytes in this context has allowed this challenge to be met without several of the limitations connected with the use of split-thickness skin grafts. The continuous development of this novel approach has now revealed that transplantation of cultured autologous keratinocytes as single-cell suspensions exhibits several advantages over the use of cultured epidermal grafts. However, a number of methodological problems remain to be solved, primarily with regards to the complexity of culturing these cells, loss of viability and other negative effects during their preparation and transportation, the relatively long period of time required following transplantation to obtain a sufficiently protective epidermis. In the present investigation we attempted to eliminate these limitations by culturing the keratinocytes on macroporous gelatin spheres. Accordingly, the efficacies of normal human keratinocytes in single-cell suspension or growing on macroporous gelatin spheres, as well as of split-thickness skin grafts in healing wounds on athymic rats were compared. Human keratinocytes were found to adhere and proliferate efficiently both on the surface and within the pores of such spheres. Transplantation of such cells adherent to the spheres resulted in significantly more rapid formation of a stratified epidermis than did transplantation of single-cell suspensions or spheres alone. Twenty-three days after transplantation, the epidermis formed from the cells bound to the spheres was not as thick as the epidermis on wounds covered with split-thickness skin grafts, but significantly thicker than on wounds to which single-cell suspensions, spheres alone or no transplant at all was applied. Furthermore, fluorescence in situ hybridisation revealed that the transplanted keratinocytes, both those adherent to gelatin spheres and those in single-cell suspension, were components of the newly formed epidermis. These findings indicate that application of biodegradable macroporous spheres may prove to be of considerable value in designing cell-based therapies for the treatment of acute and persistent wounds. © 2006 Elsevier Ltd and ISBI.
Tracer studies on motor axons after nerve crush injuries have indicated that misrouting may occur even when the endoneurium is intact. Misrouting of regenerated polymodal nociceptive C-fibres and low threshold mechanoreceptive axons have been studied functionally in 50 rats three months after unilateral crush lesions to the sciatic nerve. Two weeks before evaluation the tibial fascicle (or the peroneal fascicle) above the lesion was cut and tied off. In this way only functional regeneration of misrouted axons was tested. Misrouted low threshold mechanoreceptive axons and polymodal nociceptor C-fibres were found after regeneration in both glabrous and hairy skin. We conclude that functional misdirection of both myelinated and unmyelinated sensory axons innervating either glabrous or hairy skin can occur after a crush lesion to a peripheral nerve in rats. © 2005 Taylor & Francis.
Retroauricular tissue for reconstruction of external nasal defects was described by Washio. We describe our recent experiences in elderly patients, in whom the risk of reconstruction after excision of a malignant growth is high. We present seven reconstructions, six after excision of malignant disease, together with our ideas about how to maximise its possibilities. © 2005 Taylor & Francis.
In Sweden, approximately 6% of all human transportation is made via buses. The Swedish Board of Accident Investigation and the Swedish Rescue Services Agency have pointed out repeatedly that buses are potential fire and burn hazards, not only when involved in collisions but also in other circumstances. The number of fire incidents is increasing, especially in newer buses. In conjunction with the Swedish Rescue Services Agency, we examined some of the recent bus fires in Sweden. We did not find any casualties, but the results of our study suggest that casualties as a result of bus fires are imminent unless preventive measures are taken. We also studied experiences from previous bus fires and suggest preventive measures.
Objective. To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. Material and methods. Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). Results. During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p andlt; 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p andlt; 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p andlt; 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). Conclusions. Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.
Objective. To study residual tumours at second-look resection in patients resected 4-8 weeks earlier for T1 tumours of the urinary bladder. Material and methods. All patients randomized in the ongoing Nordic T1G2-G3 Bladder Sparing Study with monitored data available were included in the study. Data on residual tumours at second-look resection were compared to basic patient and tumour characteristics. Results. There were 72 patients (56%) without and 57 with residual exophytic tumours. In the former group, 20 patients (28%) had carcinoma in situ, compared to 19 (33%) in the latter group. Potentially dangerous tumours (either carcinoma in situ, T1 or Ta grade 3) were observed in 55 patients (43%). Multiple tumours at primary resection were more prone to residual tumour at second-look resection than single tumours. No other tumour or patient characteristics could predict the occurrence of a residual tumour. Conclusions. Residual tumours are frequently observed at second-look resection 4-8 weeks after primary resection of T1 tumours. The majority of residual tumours detected at this stage are potentially dangerous, therefore, early second-look resection followed by intravesical instillation therapy is mandatory in patients with T1 tumours of the urinary bladder. © 2005 Taylor & Francis.
PUMA is a BH3-only member of the Bcl-2 family, up-regulated by p53 as a response to DNA damage. We have investigated the mRNA expression of PUMA with real-time PCR in 94 colorectal adenocarcinomas and the corresponding normal mucosa. Among them PUMA protein expression was investigated with immunohistochemistry in 23 tumours and 17 corresponding normal mucosa samples. The mRNA expression of PUMA decreased in 4% and increased in 4% of the tumours compared with the normal mucosa. The protein expression of PUMA decreased in 6% and increased in 29% of the tumours compared with the normal mucosa. Decreased PUMA expression in the tumour compared with the corresponding mucosa was correlated with the distal colon and rectum (P=0.02). We did not find any other relationship to clinical or pathological features. We suggest that the changes in PUMA expression may be of minor importance in the development of colorectal cancer.
The nature of pancreatic acinar metaplasia (PAM) in the gastro-oesophageal junction (GOJ) remains obscure. We aimed to estimate its prevalence and investigate into its risk factors in a population-based series of first-time endoscopy patients. We investigated consecutive patients, endoscoped for the first time, representing defined catchment area populations. Biopsies were taken immediately below the GOJ and from the distal oesophagus. Endoscopy room-based cross-sectional clinical data were supplemented with exposure data from 160 population controls. Associations, expressed as odds ratios (OR), were modelled with multivariable logistic regression. A subsample of 26 patients underwent oesophageal pH monitoring. Among 644 patients (mean age 53 years, 43% men), PAM was found in 121 patients (19%), exclusively above the GOJ in 40 (6%), below GOJ in 67 (10%), and both above and below GOJ in 14 (2%). PAM exclusively above the GOJ and PAM exclusively below the GOJ were both borderline associated with age (2% increase in prevalence per year). PAM exclusively above the GOJ was significantly associated with female gender (OR 2.8, 95% CI 1.3-6.3) and presence of Helicobacter pylori immediately below the GOJ (OR 2.6, 95% CI 1.3-5.4). Out of 21 patients with Barretts oesophagus (BO), 8 (38%) had PAM above the GOJ. The mean value for percentage time with oesophageal pH andlt; 4.0 was 7.3% (95% CI 4.3-10.2%) among patients who had PAM above the GOJ (reference value 3.4%). Pancreatic acinar metaplasia might be an age-dependent lesion, associated with H. pylori, female gender and gastro-oesophageal reflux if located above the GOJ.
Objective. The epidemiology of Barrett's oesophagus (BO) is characterized by divergent results. The aim of this study was to estimate the prevalence of BO and intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ) in a population-based series of patients referred for first-time gastroscopy. Material and methods. Consecutive patients who underwent endoscopy for the first time at endoscopy units exclusively serving defined catchment areas were invited to take part in the study. Biopsies were taken immediately below the GOJ and from the distal oesophagus, and clinical data were recorded. Results. A total of 769 patients (mean age 53 years, 43% M) were examined. Overall IM prevalence was 14%. BO was noted in 4%. Overall, the prevalence of IM increased by 8% (95% CI 6-10%) per year of age. BO patients were predominately women (69%). Presence of cardia-type mucosa in the cardia increased with age from 25% among the youngest to 59% among the oldest patients. Pancreatic acinar metaplasia (PAM) was found in 18%. Conclusions. While BO is not common among Swedish gastroscopy patients, IM and PAM are found in every 7th and 6th patient, respectively. Age-dependent increments in prevalence suggest that not only BO and IM, but also cardia-type mucosa are acquired and/or progressive lesions. © 2005 Taylor & Francis.
Background: The relationship between appendectomy and Crohn's disease is controversial. A Swedish-Danish cohort study was conducted to assess the risk of developing Crohn's disease after an appendectomy. Methods: 709 353 appendectomy patients in Sweden (since 1964) and Denmark (since 1977) were followed for first hospitalisations for Crohn's disease to 2004. Standardised incidence ratios (SIR) served as relative risks. Results: Overall, 1655 Crohn's disease cases were observed during 11.1 million person-years of follow-up. Whereas appendectomy before the age of 10 years was not associated with the risk of Crohn's disease (SIR 1.00, 95% CI 0.80-1.25), the overall SIR of developing Crohn's disease was 1.52 (95% CI 1.45-1.59), being highest in the first 6 months (SIR 8.69, 95% CI 7.68-9.84). SIR diminished rapidly thereafter, with the risk of Crohn's disease reaching background levels after 5-10 years for Crohn's disease overall, as well as for Crohn's ileitis, ileocolonic Crohn's disease, Crohn's colitis and other/unspecified Crohn's disease. A long-term increased risk of Crohn's disease up to 20 years after the appendectomy was seen only in appendectomy patients without appendicitis or mesenteric lymphadenitis. Conclusion: The transient increased risk of Crohn's disease after an appendectomy is probably explained by diagnostic bias.
Studies using a contusion trauma model have shown that the femoral artery of the rat remains patent in 85% despite a severe vessel injury. A significant increase in tissue oxygenation (PtO2) has been found despite only a minor effect on blood flow (<20% decrease) on the muscle surface distal to the injury indicating a disturbed relationship between microvascular blood flow and metabolism. The aim of the present study was to further study the interplay between microvascular blood flow and metabolism within the distal muscle using an ethanol clearance technique (blood flow) in conjunction to the determination of an ischemia marker (lactate) by use of microdialysis. Although skeletal muscle blood flow remained unaltered as assessed by ethanol clearance, skeletal muscle lactate levels increased significantly (P < 0.001) post-trauma in both legs. The increase was initially higher, faster and the increase over time larger in the trauma leg as compared to the control leg (P < 0.001). These findings indicate a systemic effect of the trauma. Further, it suggests a functional impairment of the relationship between microvascular blood flow and/or muscle metabolic processes when the trauma is directed towards the supplying blood vessel. The reason for this anaerobic insult as found in this study compared to the presence of a local increase in PtO2 in the trauma leg as shown in our previous study is suggestive of an microvascular blood flow and tissue metabolism uncoupling. © 2005 Elsevier Inc. All rights reserved.