| 1. |
- Abrahamsson, Johan, et al.
(författare)
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Complete metabolic response with [18F]fluorodeoxyglucose-positron emission tomography/computed tomography predicts survival following induction chemotherapy and radical cystectomy in clinically lymph node positive bladder cancer
- 2022
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 129:2, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether repeated [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET-CT) scans can predict increased cancer-specific survival (CSS) after induction chemotherapy followed by radical cystectomy (RC). Patients and Methods: Between 2007 and 2018, 86 patients with clinically lymph node (LN)-positive bladder cancer (T1–T4, N1–N3, M0–M1a) were included and underwent a repeated FDG-PET-CT during cisplatin-based induction chemotherapy. The 71 patients that had a response to chemotherapy underwent RC. Response to chemotherapy was evaluated in LNs through repeated FDG-PET-CT and stratified as partial response or complete response using three different methods: maximum standardised uptake value (SUVmax), adapted Deauville criteria, and total lesion glycolysis (TLG). Progression-free survival (PFS) and CSS were analysed for all three methods by Cox regression analysis. Results: After a median follow-up of 40 months, 15 of the 71 patients who underwent RC had died from bladder cancer. Using SUVmax and the adapted Deauville criteria, multivariable Cox regression analyses adjusting for age, clinical tumour stage and LN stage showed that complete response was associated with increased PFS (hazard ratio [HR] 3.42, 95% confidence interval [CI] 1.20–9.77) and CSS (HR 3.30, 95% CI 1.02–10.65). Using TLG, a complete response was also associated with increased PFS (HR 5.17, 95% CI 1.90–14.04) and CSS (HR 6.32, 95% CI 2.06–19.41). Conclusions: Complete metabolic response with FDG-PET-CT predicts survival after induction chemotherapy followed by RC in patients with LN-positive bladder cancer and comprises a novel tool in evaluating response to chemotherapy before surgery. This strategy has the potential to tailor treatment in individual patients by identifying significant response to chemotherapy, which motivates the administration of a full course of induction chemotherapy with a higher threshold for suspending treatment due to toxicity and side-effects.
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| 2. |
- Bobjer, Johannes, et al.
(författare)
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Location of retroperitoneal lymph node metastases in upper tract urothelial carcinoma : results from a prospective lymph node mapping study
- 2023
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 57, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND).Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node–positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates.Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.
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| 3. |
- Brändstedt, Johan, et al.
(författare)
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Urosymphyseal fistula after pelvic radiotherapy in a tertial referral centre : a rare entity with significant comorbidity requiring multidisciplinary management
- 2023
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 58, s. 4-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report population-based clinical presentation and outcomes in patients with urosymphyseal fistula (USF) after pelvic radiotherapy (RT).Patients and methods: A retrospective chart review was performed in 33 consecutive patients diagnosed with suspicion of USF in a tertial referral center from 2014–2022 to ascertain information about diagnostic delay, clinical presentation, precipitating causes, treatments received and outcomes during the median 22 months follow-up. Out of 33 consecutive patients with suspicion of USF, one female with vesicovaginal fistula, one patient developing RT-associated bladder angiosarcoma, four patients with short follow-up (<3 months), and three patients that during chart review not were considered to have a USF were excluded.Results: In all, 24 males with a median age of 77 years were diagnosed with USF. Local pain was the predominating symptom in 17/24 (71%) patients. Endourologic manipulations preceded the diagnosis of USF in 16 patients. Five patients had a diagnostic delay of more than 3 months. At diagnosis, 20/24 patients had radiological signs of osteomyelitis, and five had a concomitant rectourethral fistula. Due to comorbidity, five patients were not amenable to any other interventions than urinary catheter or suprapubic tube in conjunction with long-term antibiotics, of which three died from infections related to the USF. Out of the remaining 19 patients receiving some form of urinary diversion, five had recurrent osteomyelitis, of which four did not undergo cystectomy in conjunction with surgery for the USF.Conclusions: Urethral endourologic interventions in patients previously subjected to pelvic RT should be performed cautiously.
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| 4. |
- Böös, Malin, et al.
(författare)
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Who should record surgical complications? : Results from a third-party assessment of complications after radical cystectomy
- 2019
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 339-343
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.
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| 7. |
- Jia, Xiaohui, et al.
(författare)
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Exendin-4 Increases the Expression of Hypoxia-InducibleFactor-1 in Rat Islets and Preserves the Endocrine CellVolume of Both Free and Macroencapsulated Islet Grafts
- 2012
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Ingår i: Cell Transplantation. - 0963-6897. ; 21:6, s. 1269-1283
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we evaluated the effects of exendin-4 on free and encapsulated islet grafts in a rodent model.We also investigated the role of a transcription factor, hypoxia-inducible factor-1 (HIF-1), in mediating thebeneficial effects of exendin-4. Diabetic athymic mice were transplanted with free rat islets under the kidneycapsule or with macroencapsulated rat islets SC with or without exendin-4, islet preculture (exendin-4 0.1nM for 20 h), and/or recipient treatment (IP 100 ng/day, day 0–7). The mice were followed for 4 weeks andthe graft function andβ-cell volume were evaluated. The effects of exendin-4 on islet HIF-1α mRNAand protein expression and on ATP content in a rat insulinoma cell line (INS-1E) were also examined.Preculture with exendin-4 followed by recipient treatment improved the outcome of both free (73% graftfunction vs. 26% in controls,p = 0.03) and macroencapsulated islet grafts (100% vs. 25% in controls, p =0.02). In macroencapsulated grafts, the exendin-4-treated group had significantly larger endocrine volume,less graft necrosis, and more blood vessels around the capsule. In rat islets cultured with exendin-4, HIF-1αmRNA and protein expression were significantly enhanced. ATP content was increased in exendin-4-treatedINS-1E cells under hypoxic conditions. The improved functional outcome after transplantation of a marginalislet mass with a brief initial treatment with exendin-4 is related to a larger surviving endocrine cell volume.Exendin-4 may improve islet graft resistance to hypoxia during the peritransplant period by increasing theexpression of HIF-1
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| 8. |
- Liedberg, Fredrik, et al.
(författare)
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Anorectal dysfunction after radical cystectomy for bladder cancer
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:2, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To prospectively assess anorectal dysfunction using patient-reported outcomes using validated questionnaires, manovolumetry and endoanal ultrasound before and 12 months after RC. Patients and methods: From 2014 to 2019, we prospectively included 44 patients scheduled for RC. Preoperatively and 12 months after surgery, 41 patients filled in a low anterior resection syndrome score (LARS-score) to assess fecal incontinence, increased frequency, urgency and emptying difficulties and a St Mark’s score to assess fecal incontinence in conjunction with manovolumetry and endoanal ultrasound examinations. Pre- and postoperative patient-reported anorectal dysfunction were assessed by LARS-score and St Marks’s score. At the same time-points, anorectal function was evaluated by measuring mean anal resting and maximal squeeze pressures, volumes and pressures at first desire, urgency to defecate and maximum toleration during manovolumetry. Wilcoxon's signed rank test was used to compare pre- and postoperative outcomes by questionnaires. Results: Postoperatively 6/41 (15%) patients reported flatus incontinence assessed by the LARS-questionnaire, and correspondingly the St Mark’s score increased postoperatively. The median anal resting pressure decreased from 57 mmHg preoperatively to 46 mmHg after RC, but without any postoperative anatomic defects detected by endoanal ultrasound. Volumes and pressures at first desire, urgency to defecate and maximum toleration during manovolumetry all increased after RC, indicating decreased postoperative rectal sensation, as rectal compliance was unaltered. Conclusions: Postoperative flatus incontinence is reported by one out of seven patients after RC, which corresponds to decreased anal resting pressures. The finding of decreased rectal sensation might also contribute to patient-reported symptoms and anorectal dysfunction after RC.
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| 9. |
- Liedberg, Fredrik, et al.
(författare)
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Preventing Parastomal Hernia After Ileal Conduit by the Use of a Prophylactic Mesh : A Randomised Study
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 78:5, s. 757-763
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parastomal hernia (PSH) after urinary diversion with ileal conduit is frequently a clinical problem.OBJECTIVE: To investigate whether a prophylactic lightweight mesh in the sublay position can reduce the cumulative incidence of PSH after open cystectomy with ileal conduit.DESIGN, SETTING, AND PARTICIPANTS: From 2012 to 2017, we randomised 242 patients 1:1 to conventional stoma construction (n = 124) or prophylactic mesh (n = 118) at three Swedish hospitals (ISRCTN 95093825).OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was clinical PSH, and secondary endpoints were radiological PSH assessed in prone position with the stoma in the centre of a ring, parastomal bulging, and complications from the mesh.RESULTS AND LIMITATIONS: Within 24 mo, 20/89 (23%) patients in the control arm and 10/92 (11%) in the intervention arm had developed a clinical PSH (p = 0.06) after a median follow-up of 3 yr, corresponding to a hazard ratio of 0.45 (confidence interval 0.24-0.86, p = 0.02) in the intervention arm. The proportions of radiological PSHs within 24 mo were 22/89 (25%) and 17/92 (19%) in the two study arms. During follow-up, five patients in the control arm and two in the intervention arm were operated for PSH. The median operating time was 50 min longer in patients receiving a mesh. No differences were noted in proportions of Clavien-Dindo complications at 90 d postoperatively or in complications related to the mesh during follow-up.CONCLUSIONS: Prophylactic implantation of a lightweight mesh in the sublay position decreases the risk of PSH when constructing an ileal conduit without increasing the risk of complications related to the mesh. The median surgical time is prolonged by mesh implantation.PATIENT SUMMARY: In this randomised report, we looked at the risk of parastomal hernia after cystectomy and urinary diversion with ileal conduit with or without the use of a prophylactic mesh. We conclude that such a prophylactic measure decreased the occurrence of parastomal hernias, with only a slight increase in operating time and no added risk of complications related to the mesh.
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| 14. |
- Liedberg, Fredrik, et al.
(författare)
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Should we Refrain from Performing Oophorectomy in Conjunction with Radical Cystectomy for Bladder Cancer?
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 71:6, s. 851-853
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Tidskriftsartikel (refereegranskat)abstract
- Radical cystectomy with neoadjuvant chemotherapy is the gold standard for treating muscle-invasive bladder cancer. Women subjected to radical cystectomy are frequently postmenopausal, and the median age for bladder cancer diagnosis in women in Sweden is currently 73 yr (Swedish National Bladder Cancer Register). Traditionally, most women treated with radical cystectomy have undergone simultaneous bilateral oophorectomy and hysterosalpingectomy to diminish the risk of later ovarian disease and ovarian bladder cancer recurrence, but also the belief that there is no impact on health or health-related quality of life associated with oophorectomy and the fact that it might be easier surgery to take the ovarian pedicles, rather than sparing the ovaries. However, pelvic organ preservation is considered in some younger women to diminish postoperative functional impairment. Based on recent literature in several areas related to oophorectomy, we question the rationale and arguments for performing oophorectomy in women in conjunction with radical cystectomy for bladder cancer. It can be questioned whether routine bilateral oophorectomy during radical cystectomy is advisable in premenopausal women, and the same might also apply to selected postmenopausal women.
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| 15. |
- Sörenby, Anne, et al.
(författare)
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Reducing recurrence in non-muscle-invasive bladder cancer by systematically implementing guideline-based recommendations : effect of a prospective intervention in primary bladder cancer patients
- 2019
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:2-3, s. 109-115
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In non-muscle-invasive bladder cancer (NMIBC), local recurrence after transurethral resection of the bladder (TURB) is common. Outcomes vary between urological centres, partly due to the sub-optimal surgical technique and insufficient application of measures recommended in the guidelines. This study evaluated early recurrence rates after primary TURB for NMIBC before and after introducing a standardized treatment protocol. Methods: Medical records of all patients undergoing primary TURB for NMIBC in 2010 at Skåne University Hospital, Malmö, Sweden, were reviewed. A new treatment protocol for NMIBC was defined and introduced in 2013, and results documented during the first year thereafter were compared with those recorded in 2010 prior to the intervention. The primary endpoint was early recurrence at first control cystoscopy. Comparisons were made by Chi-square analysis and Fisher’s exact test. Recurrence-free survival (RFS) in the two cohorts was also investigated. Results: TURB was performed on 116 and 159 patients before and after the intervention, respectively. The early recurrence rate decreased from 22% to 9.6% (p = 0.005) at the first control cystoscopy after treatment. Residual/Recurrent tumour at the first control cystoscopy after the primary TURB (i.e. at second-look resection or first control cystoscopy) decreased from 31% to 20% (p = 0.038). The proportion of specimens containing muscle in T1 tumours increased from 55% to 94% (p < 0.001). RFS was improved in the intervention group (HR = 0.65, CI = 0.43–1.0; p = 0.05). Conclusions: Introduction of a standardized protocol and reducing the number of surgeons for primary treatment of NMIBC decreased the early recurrence rate from 22% to 9.6% and lowered the recurrence incidence by 35%.
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| 16. |
- Sörenby, Anne
(författare)
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Strategies to improve macroencapsulated islet graft survival
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic immunosuppressive therapy may have severe side-effects. In cell transplantation, the graft can be encapsulated within a membrane chamber, providing a physical barrier against the immune system. The cell graft then becomes dependent on the diffusion of nutrients and oxygen from the surrounding microcirculation. A major drawback has been the formation of avascular fibrotic tissue around the chamber. The immunoprotective device studied (TheraCyte ) has an outer membrane inducing neovascularization. However, major parts of the encapsulated graft are still lost soon after transplantation, probably because of relative hypoxia and malnutrition. The overall aim of this thesis was to assess various strategies to improve islet graft survival in the device, using rodent models. The purpose of the first paper was to improve the method for histological evaluation of the vascularization around the device. Vascular profiles within various distances from the membrane surface were counted at different times and then correlated with glucose kinetics. We found that the vascular profiles within 100 ìm had the highest correlations with glucose kinetics and concluded that vessels within this distance are important for the exchange of small molecules between the circulation and the device s lumen. Therefore, we recommend that 100 ìm should be used in histological evaluations of the membrane vascularization. In the second paper we hypothesized that preimplantation of the device should improve encapsulated islet graft survival. Previous studies have indicated that it takes up to 3 months for recovery of the microcirculation after membrane implantation. Therefore, we implanted empty devices and transplanted islets 3 months later in these chambers. This approach significantly improved the cure rates of diabetic animals, and the islet dose required for cure was reduced by about 10 times. Morphometry evaluations confirmed increased graft survival in preimplanted devices. The third paper aimed at evaluating the effects of exendin-4 treatment on the metabolic outcome after islet transplantation. Exendin-4 inhibits islet apoptosis, stimulates islet differentiation and regeneration and has beneficial effects on peripheral tissues. We found that exendin-4 treatment significantly improved the metabolic outcome after free islet transplantation to the renal subcapsular site. The benefit lasted longer than the treatment, suggesting that exendin-4 had long-standing effects on the islet graft. This substance seems to be an interesting new approach to improve the survival also of encapsulated islet grafts. In the last paper we evaluated the risk of recipient sensitization using macroencapsulated islets. A heterotopic heart graft was transplanted one month after free or encapsulated islet transplantation. The time-to-rejection was significantly shorter in the free islet group, while it did not differ between encapsulated islet graft recipients and naive animals. We therefore conclude that the device protects against sensitization, at least during the first month after transplantation. Today, side-effects of the immunosuppressive therapy are one of the main limiting factors for the use of islet transplantation. If immunoprotection could be achieved by encapsulation of the islet graft, it should be possible to widen the indications. This thesis describes promising strategies to improve the survival of macroencapsulated islet grafts, which might contribute to make macroencapsulation a clinical reality.
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