| 1. |
- Andersson, M., et al.
(författare)
-
Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis
- 2023
-
Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 64:1, s. 32-41
-
Tidskriftsartikel (refereegranskat)abstract
- Background Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. Purpose To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. Material and Methods A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. Results The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). Conclusion DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.
|
|
| 2. |
- Ben-Shabat, Ilan, et al.
(författare)
-
Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma.
- 2015
-
Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :95
-
Tidskriftsartikel (refereegranskat)abstract
- Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.
|
|
| 3. |
- Fehrman-Ekholm, Ingela, 1947, et al.
(författare)
-
Incidence of end-stage renal disease among live kidney donors.
- 2006
-
Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 82:12, s. 1646-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The increasing use of living kidney donors requires knowledge about long-term effects, especially number and causes of donors with end-stage renal disease (ESRD). METHODS: A retrospective data analysis of 1,112 consecutive living kidney donors who underwent nephrectomy from 1965 until 2005 at Sahlgrenska University Hospital. Case reports were sought with help from nephrologists in the region and data from Swedish Registry of Active Uremic Treatment (SRAU). RESULTS: The number of cases with end stage kidney failure among living kidney donors was 6/1112, that is 0.5%. The donors had reached ESRD during the years 2001-2006, that means 36-41 years after start of the living donor program. The donors were 45-89 years old, median 77 years, and five of six were males. Time since donation was 14-27 years, median 20 years, for the donors developing ESRD. The diagnoses were nephrosclerosis (4 cases), postrenal failure (1 case), and renal carcinoma (1 case). The expected incidence for development of ESRD according to incidence in the general population would have been two donors but we found six. However, considering the high age of the donors in this follow up, the age-matched incidence is calculated to be closer to six donors due to higher incidence in the aged. CONCLUSION: In all 0.5% of the donors developed ESRD. Due to high age of the uremic donors, there seems to be no increased incidence.
|
|
| 4. |
|
|
| 5. |
- Fehrman-Ekholm, Ingela, 1947, et al.
(författare)
-
Post-nephrectomy development of renal function in living kidney donors: a cross-sectional retrospective study
- 2011
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 26:7, s. 2377-2381
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increasing numbers of living donor kidney transplantations calls for better knowledge about long-term donor outcomes and risks. METHODS: To explore long-term kidney donor outcomes and risks, we conducted a cross sectional retrospective study. To this end, we analysed renal function using measured glomerular filtration rate (mGFR) and estimated glomerular filtration rate (eGFR) as well as microalbuminuria, blood pressure (BP), body mass index, haemoglobin, albumin and parathyroid hormone in kidney donors nephrectomized between 1965 and 2005. RESULTS: A total number of 573 kidney donors agreed to undergo medical follow-up examinations. The mean age (standard deviation) at donation was 47 (11) years and the mean time since donation was 14 (9) years. Both mean mGFR [68 (15) mL/min/1.73m(2) body surface; P = 0.028] and mean eGFR [71 (16) mL/min/1.73m(2) body surface; P < 0.001], based on modified diet renal dysfunction and iohexol or Cr-EDTA clearance, respectively, were found to decrease with age and to increase with time since donation. Special multivariable regression analyses reveal that for 30-year old donors, the median eGFR typically increases during the first 17 years, then remains constant for ∼8 years and slowly declines thereafter. For 50-year-old donors, the median eGFR is expected to increase during the first 15 years or so and then to enter a phase of slight progressive decline. In total, 23% (126/546) of the donors were on antihypertensive medication. An additional 22% (117/543) of the donors were found to suffer from hitherto undiagnosed hypertension (BP >140/90 mm Hg). CONCLUSION: Renal function of the remaining kidney in living donors is expected to improve for many years but will show signs of slight deterioration in the longer run.
|
|
| 6. |
- Fistouris, Johan, et al.
(författare)
-
Pseudoaneurysm of the hepatic artery following liver transplantation
- 2006
-
Ingår i: Transplantation proceedings. - 0041-1345. ; 38:8, s. 2679-82
-
Tidskriftsartikel (refereegranskat)abstract
- We report 12 cases of pseudoaneurysm hepatic artery (PA) among 825 liver transplantations (OLT) performed between January 1985 and December 2005. In the early period (1985 to 1995), the incidence was 2.6% and in the later period (1996 to 2005), 0.9%. Median time to onset was 39.5 days post-OLT (range 14 days to 5 years). Six patients presented with rupture into the peritoneum (n = 4) or gastrointestinal tract (n = 2), while five patients presented with gastrointestinal bleed due arteriobiliary fistulation with hemobilia. The twelfth PA was found incidentally during retransplantation. PAs were detected with radiological imaging (n = 4), exploratory laparotomy (n = 6), at autopsy (n = 1) or at retransplantation (n = 1). We performed immediate revascularization, after surgical excision was performed in three and endovascular embolization in one patient. In six patients hepatic artery ligation without revascularization was inevitable with subsequent successful retransplantation in four patients. No PA-specific treatment was attempted in two cases due to the poor prognosis or diagnostic ambiguity. In 10 cases microbial pathogens were cultured in the blood, subhepatic abscesses, or from the wall of the hepatic artery. A hepaticojejunostomy was performed for biliary reconstruction in six patients and two had a hepaticojejunostomy conversion due to biliary leak. Survival in the early period (1985 to 1995) was 14%, whereas during the later period (1996 to 2005), the survival increased to 100% with a 4.2-year median follow-up (range 7.4 months to 6.9 years). Infrequently PA complicates OLT, becoming evident primarily after rupture with hemoperitoneum or a gastrointestinal bleed. Early recognition with angiography is important but acute hemorrhage often requires immediate exploration with ligation of the PA, although surgical or endovascular exclusion of the PA followed by revascularization provides a feasible treatment option.
|
|
| 7. |
- Flodén, Anne, 1957, et al.
(författare)
-
Attitudes to organ donation among Swedish ICU nurses.
- 2011
-
Ingår i: Journal of clinical nursing. - : Wiley. - 1365-2702 .- 0962-1067. ; 20:21-22, s. 3183-95
-
Tidskriftsartikel (refereegranskat)abstract
- To present data on Swedish ICU nurses' attitudes to brain death and organ donation and to test a questionnaire designed to explore these issues in terms of validity and reliability.
|
|
| 8. |
- Flodén, Anne, 1957, et al.
(författare)
-
Development and Psychometric Evaluation of the Instrument: Attitudes Towards Organ Donor Advocacy Scale (ATODAS).
- 2011
-
Ingår i: The open nursing journal. - : Bentham Science Publishers Ltd.. - 1874-4346. ; 5, s. 65-73
-
Tidskriftsartikel (refereegranskat)abstract
- The consequences of advocacy in nursing are critical when caring for a potential organ donor. No specific instrument has been available to measure attitudes toward organ donor advocacy. The aim of this study was to develop and psychometrically evaluate an instrument for measuring intensive and critical care (ICU) nurses' attitudes toward organ donor advocacy. The study was conducted in two stages: instrument development and instrument evaluation and refinement. A questionnaire was developed (Attitude Toward Organ Donor Advocacy Scale (ATODAS)), which was sent to half of all nurses working in ICUs (general-, neuro-, thoracic- or paediatric-) in Sweden (n=1180). The final response rate was 42.5% (n=502). In order to explore validity and reliability, the expected scale dimensionality of the questionnaire was examined both by explorative principal component analysis (with oblique, varimax rotation) and by confirmatory multi-trait analysis. The confirmatory factor analysis indicated that the ATODAS could best be explained by five factors; Attitudes toward championing organ donation at a structural hospital level; Attitudes toward championing organ donation at a political and research level; Attitudes toward actively and personally safeguarding the will and wishes of the potential organ donor, Attitudes toward safeguarding the potential donor's will and wishes by a professional approach and Attitudes toward safeguarding the will and wishes of the relatives. This initial testing indicated that the ATODAS has good psychometric properties and can be used in future research to explore if interventions may influence attitudes and behaviors related to organ donor advocacy.
|
|
| 9. |
- Forsberg, Anna, et al.
(författare)
-
Attitudes towards organ donor advocacy among Swedish intensive care nurses
- 2015
-
Ingår i: Nursing in Critical Care. - : Wiley. - 1362-1017 .- 1478-5153. ; 20:3, s. 126-133
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo explore the attitudes of Swedish intensive care nurses towards organ donor advocacy. BackgroundThe concept of organ donor advocacy is critical to nurses who care for potential donors in order to facilitate organ donation (OD). MethodsInclusion criteria in this survey were to be a registered nurse and to work in a Swedish intensive care unit (ICU). Participants were identified by the Swedish association of health professionals. A number of 502 Swedish ICU nurses answered the 32-item questionnaire Attitudes Towards Organ Donor Advocacy Scale (ATODAS), covering the five dimensions of organ donor advocacy: attitudes towards championing organ donation at a structural hospital level, or at a political and research level, attitudes towards actively and personally safeguarding the will and wishes of the potential organ donor, or by using a more professional approach and finally to safeguard the will and wishes of the relatives. Data were analysed with the SPSS version 180 and the results were assessed by using Student's t-test and post hoc test, analysis of variance (ANOVA), (2), Pearson's correlation and regression analysis. ResultsThe most favoured advocacy action was safeguarding the POD's will and wishes by a professional approach, closely followed by actively and personally safeguarding the POD's will and wishes. Nurses at local hospitals reported a more positive attitude towards organ donor advocacy overall compared with nurses at larger regional or university hospitals. Important factors leading to positive attitudes were seniority, working experience, participating in conversations with relatives, caring for brain-dead persons and private experiences from OD or organ transplantation. ConclusionsIntensive and critical care nurses with short working experience in university hospitals showed the least positive attitude towards organ donor advocacy. This is problematic because many ODs and all transplantations are performed in university hospitals. Relevance to clinical practiceThis study emphasizes the importance of organizing the care of PODs and their relatives in a way that promotes advocacy.
|
|
| 10. |
- Friman, Styrbjörn, 1948, et al.
(författare)
-
Kidney transplantation--a 46-year experience from the Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
- 2011
-
Ingår i: Clinical transplants. - 0890-9016. ; , s. 119-25
-
Tidskriftsartikel (refereegranskat)abstract
- The limiting factor in organ transplantation is the availability of organs. Ongoing work to improve donation rates both at the public and the organizational level in donating hospitals is essential. We also think that encouragement of live donation is important, and the possibility of ABO incompatible transplantation has increased the number of LD transplantations. The one-year graft survival rate is excellent and focus has shifted towards achieving long-term results to reduce the attrition rate. There is also an increasing interest in studying and working to reduce comorbidities on a long-term basis and thus, improve survival rates and recipient quality of life.
|
|
| 11. |
- Friman, Styrbjörn, 1948, et al.
(författare)
-
Liver transplantation for cholangiocarcinoma: Selection is essential for acceptable results.
- 2011
-
Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:3, s. 370-375
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Background and aims. Cholangiocarcinoma (CCA) is considered a contraindication for liver transplantation by most liver transplant centers. The aim of this study has been to report our results as well as to explore factors that influence patient survival after liver transplantation for CCA. Patients. All transplant patients with CCA in Norway, Sweden and Finland during 1984-2005 were included (n = 53). Thirty-three patients (62%) had intrahepatic CCA. Twenty-one patients (40%) had a more advanced tumor (>TNM stage 2). Thirty-four of the 53 recipients (64%) had primary sclerosing cholangitis (PSC). Results. Patients with TNM stage ≤2 transplanted after 1995 had a 5-year survival rate of 48%. The overall 5-year patient survival rate was 25%. There was no difference in survival between patients with extrahepatic and intrahepatic CCA. The 5-year survival rate among patients with TNM stage ≤2 was 36%. Patients with TNM stage >2 had a 10% 5-year survival rate; the difference was significant at p < 0.01. Patients transplanted after 1995 had a significantly better 5-year survival rate than pre-1995 patients (38% vs. 0%, p < 0.01). Patients transplanted after 1995 with TNM ≤2 and CA 19-9 ≤100 had the 5-year survival of 58%. Conclusion. By selecting CCA patients with TNM stage ≤2 and a CA 19-9 ≤100 a reasonable 5-year survival rate is possible. We think that CCA in selected cases can be an acceptable indication for liver transplantation.
|
|
| 12. |
- Gilg, Stefan, et al.
(författare)
-
The impact of post-hepatectomy liver failure on mortality : a population-based study
- 2018
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:10-11, s. 1335-1339
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers.Aim: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy.Method: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5.Results: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3.Conclusion: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.
|
|
| 13. |
- Hansdotter, P., et al.
(författare)
-
Patterns and resectability of colorectal cancer recurrences: outcome study within the COLOFOL trial
- 2021
-
Ingår i: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improvements in surgery, imaging, adjuvant treatment, and management of metastatic disease have led to modification of previous approaches regarding the risk of recurrence and prognosis in colorectal cancer. The aims of this study were to map patterns, risk factors, and the possibility of curative treatment of recurrent colorectal cancer in a multimodal setting. METHODS: This was a cohort study based on the COLOFOL trial population of patients who underwent radical resection of stage II or III colorectal cancer. The medical files of all patients with recurrence within 5years after resection of the primary tumour were scrutinized. Follow-up time was 5years after the first recurrence. Primary endpoints were cumulative incidence, site, timing, and risk factors for recurrence, and rate of potentially curative treatment. A secondary endpoint was survival. RESULTS: Of 2442 patients, 471 developed recurrences. The 5-year cumulative incidence was 21.4 (95 per cent c.i. 19.5 to 23.3) per cent. The median time to detection was 1.1years after surgery and 87.3 per cent were detected within 3years. Some 98.2 per cent of patients who had potentially curative treatment were assessed by a multidisciplinary tumour board. A total of 47.8 per cent of the recurrences were potentially curatively treated. The 5-year overall survival rate after detection was 32.0 (95 per cent c.i. 27.9 to 36.3) per cent for all patients with recurrence, 58.6 (51.9 to 64.7) per cent in the potentially curatively treated group and 7.7 (4.8 to 11.5) per cent in the palliatively treated group. CONCLUSION: Time to recurrence was similar to previous results, whereas the 21.4 per cent risk of recurrence was somewhat lower. The high proportion of patients who received potentially curative treatment, linked to a 5-year overall survival rate of 58.6 per cent, indicates that it is possible to achieve good results in recurrent colorectal cancer following multidisciplinary assessment.
|
|
| 14. |
- Hansdotter, Pernilla, et al.
(författare)
-
Treatment and survival of patients with metachronous colorectal lung metastases
- 2023
-
Ingår i: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 127:5, s. 806-814
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The lungs are the second most common site for metachronous metastases in colorectal cancer. No treatment algorithm is established, and the role of adjuvant chemotherapy is unclear. This study aimed to map pulmonary recurrences in a modern multimodal treated population, and to evaluate survival depending on management.Methods: Retrospective study based on the COLOFOL-trial population of 2442 patients, radically resected for colorectal cancer stage II-III. All recurrences within 5 years were identified and medical records were scrutinized.Results: Of 165 (6.8%) patients developing lung metastases as first recurrence, 89 (54%) were confined to the lungs. Potentially curative treatment was possible in 62 (37%) cases, of which 33 with surgery only and 29 with surgery and chemotherapy combined. The 5-year overall survival (5-year OS) for all lung recurrences was 28%. In patients treated with chemotherapy only the 5-year OS was 7.5%, compared with 55% in patients treated with surgery, and 72% when surgery was combined with chemotherapy. Hazard ratio for mortality was 2.9 (95% confidence interval 1.40-6.10) for chemotherapy only compared to surgery.Conclusion: A high proportion of metachronous lung metastases after colorectal surgery were possible to resect, yielding good survival. The combination of surgery and chemotherapy might be advantageous for survival.
|
|
| 15. |
- Hasselgren, K., et al.
(författare)
-
ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
- 2021
-
Ingår i: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
|
|
| 16. |
- Hasselgren, Kristina, et al.
(författare)
-
ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
- 2021
-
Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
|
|
| 17. |
- Hasselgren, Kristina, 1976-, et al.
(författare)
-
Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO
- 2019
-
Ingår i: Journal of Gastrointestinal Surgery. - : Springer Science and Business Media LLC. - 1091-255X .- 1873-4626. ; 23:3, s. 556-562
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPortal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.MethodsPatients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) <30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.ResultsForty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (4), compared to 1.5 (+/- 2) between the first and second CT (p<0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (+/- 4) the first week, compared to 4.3 (+/- 2) for patients who failed to reach a sufficient volume (p=0.4). During the interval between the first and second CT, the KGR was 2.2 (+/- 2), respectively (+/- 0.1) (p=0.017).Discussion p id=Par4 The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.
|
|
| 18. |
- Hasselgren, Kristina, et al.
(författare)
-
Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease
- 2020
-
Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95 % CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Hemmingsson, Jens, 1986, et al.
(författare)
-
Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities
- 2018
-
Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 3:3, s. 439-446
-
Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Purpose: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materials: A patient with hepatocellular carcinoma was treated with90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.
|
|
| 23. |
|
|
| 24. |
- Hemmingsson, Jens, 1986, et al.
(författare)
-
Simulation of 90Y microspheres in selective internal radiation therapy (SIRT) reveals different heterogeneity profiles for glass and resin microspheres.
- 2016
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. 43 (Suppl 1): 1. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: Selective internal radiation therapy (SIRT) can supply normal tissue in the liver with radiation doses exceeding tolerance without causing toxicity, an effect possibly explained by microsphere clustering causing heterogeneity in the distribution. Using a simulation of microspheres transported through a simplified arterial structure, the aim of this study has been to evaluate how the number of injected microspheres affect the dose distribution. Materials and methods: The simulation was based on observations in biopsies and autoradiographies from resected liver tissue receiving 90YSIRT. Individual microspheres, with diameter and density from literature, were followed through a simplistic bifurcations model in which three parameters were introduced and optimised to obtain results consistent with observations: an artery coefficient of variation, a reduction parameter for the arterial diameter and a distribution volume parameter for the arterial tree. In the model the arterial diameter decreases for higher artery generations and the probability of microsphere clustering increases successively in the artery tree. After simulation a 90Y dose kernel was applied to the 940 cm3 sized 3D-matrix of microspheres and the dose distribution throughout the matrix was evaluated using varying resolutions and computing the coefficient of variation (CV). A smaller number of simulated microspheres (10^5) corresponds to the higher activity/sphere found in glass spheres while a larger number (10^7) resembles resin spheres. Results: As the number of microspheres increase from thousands to 106 the CV of the absorbed dose decrease from over 80 % to 32 % in a volume corresponding to a lobuli (2 mm^3) and at 106 microspheres a plateau was reached. The simulation was consistent with biopsy and autoradiography observations regarding the formation of clusters. A large majority of the clusters contain few microspheres and a minority of the clusters are significantly more numerous in microspheres. Conclusion: For the high microsphere concentrations used with resin microspheres the CVof the absorbed doses was constant (32 %) while for the lower microsphere concentrations used for glass spheres the CV varied between 90 % and 40 %. These results implies that small scale dosimetry for 90Y-SIRT differs between resin and glass spheres.
|
|
| 25. |
- Henriksson, Martin, et al.
(författare)
-
Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv
- 2020
-
Ingår i: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 4:1, s. 109-117
-
Tidskriftsartikel (refereegranskat)abstract
- Background Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. Methods Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. Results A total of 3376 patients with HCC were registered over 8 years, 246 (7 center dot 3 per cent) of whom underwent transplantation. Some 501 (14 center dot 8 per cent) and 390 patients (11 center dot 6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14 center dot 1 per cent) and 426 patients (12 center dot 6 per cent) respectively; the remaining 1337 (39 center dot 6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4 center dot 6 (i.q.r. 2 center dot 0 to not reached) years after resection and 3 center dot 1 (2 center dot 3-6 center dot 7) years following ablation. In patients referred for palliative treatment, median survival was 1 center dot 4 (0 center dot 8-2 center dot 9), 0 center dot 5 (0 center dot 3-1 center dot 2) and 0 center dot 3 (0 center dot 1-1 center dot 0) years for the TACE, sorafenib and BSC groups respectively (P amp;lt; 0 center dot 001). Median survival was 0 center dot 9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1 center dot 4 years in 2013-2016 (P amp;lt; 0 center dot 001). Conclusion The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.
|
|
| 26. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Bremsstrahlung imaging of 90Y microspheres shows poor resemblance with distributions of 99mTc-MAA in liver
- 2010
-
Ingår i: Journal of the European Society of Therapeutic Radiology and Oncology. - 0167-8140. ; 94:1, s. 25-26
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE To study the resemblance between the distributions of pre- therapeutic 99mTc-MAA and therapeutic 90Y-microspheres, used for ra- dioembolization of liver tumours, making use of gamma- and bremsstrahlung imaging. Furthermore, to establish the accuracy of this method by compar- isons of spatial resolution and radioactivity, performed on line source in water phantom and on resected tumour and normal liver from patients previously treated with 90Y-microspheres. MATERIALS 3 patients diagnosed with liver tumours and planned for surgery; 1 with hepatocellular carcinoma and 2 with cholangiocarcinoma, were treated with SIRTEX R © 90Y-microspheres after standard diagnostic SPECT/CT imag- ing with 99mTc-MAA. The images acquired with gamma camera were com- pared regarding distributions of radioactivity; gamma radiation from the 99mTc-MAA distributions and bremsstrahlung from the distributions of 90Y- microspheres (the latter with a wide bremsstrahlung energy window). Resec- tions of tumour- and some normal liver tissues were performed on all three patients; the resected tissues were sliced, smaller samples were punched out and the radioactivity was measured with a NaI-detector. Furthermore, autoradiography was performed on some slices. A line source with the in- ner diameter 1 mm was positioned in a cylindrical water phantom with the diameter 20 cm; first the line source was filled with 99mTc, then emptied and filled with 90Y. SPECT/CT imaging was performed on both line source se- tups. The spatial resolutions for both radionuclides were then compared. The results from the imaging comparisons performed on the patients were then evaluated with the complementary radiological methods described above. RESULTS The comparison of images from 99mTc-MAA and 90Y showed a considerable deviance in activity distribution for two of the patients. One ex- ample is shown in the figure, the upper image showing 99mTc-MAA and the lower showing 90Y-microspheres. The moderate difference in spatial resolu- tions for 99mTc and 90Y, (15 vs 18 mm FWHM) confirmed the accuracy of these findings. The other radiological methods did also confirm the macro- scopic activity distribution as shown with bremsstrahlung imaging. CONCLUSIONS Bremsstrahlung imaging is a satisfying and reliable method in showing the actual macroscopic distribution of therapeutic 90Y-microspheres used for radioembolization of liver tumours. The results further demonstrate the need for a better diagnostic method than the one currently used, with 99mTc-MAA, thereby providing a better pre-dosimetry; hopefully with a better selection of patients, regarding tumour regression and a lower risk of liver failure.
|
|
| 27. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy
- 2014
-
Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:48
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Selective arterial radioembolisation of liver tumours has increased, because of encouraging efficacy reports; however, therapeutic parameters used in external beam therapy are not applicable for understanding and predicting potential toxicity and efficacy, necessitating further studies of the physical and biological characteristics of radioembolisation. The aim was to characterise heterogeneity in the distribution of microspheres on a therapeutically relevant geometric scale considering the range of yttrium-90 (90Y) β-particles. METHODS Two patients with intrahepatic cholangiocarcinoma, marginally resectable, were treated by selective arterial embolisation with 90Y resin microspheres (SIRTEX®), followed 9 days post-infusion by resection, including macroscopic tumour tissue and surrounding normal liver parenchyma. Formalin-fixed, sectioned resected tissues were exposed to autoradiographic films, or tissue biopsies of various dimensions were punched out for activity measurements and microscopy. RESULTS Autoradiography and activity measurements revealed a higher activity in tumour tissue compared to normal liver parenchyma. Heterogeneity in activity distribution was evident in both normal liver and tumour tissue. Activity measurements were analysed in relation to the sample mass (5 to 422 mg), and heterogeneities were detected by statistical means; the larger the tissue biopsies, the smaller was the coefficient of variation. The skewness of the activity distributions increased with decreasing biopsy mass. CONCLUSIONS The tissue activity distributions in normal tissue were heterogeneous on a relevant geometric scale considering the range of the ionising electrons. Given the similar and repetitive structure of the liver parenchyma, this finding could partly explain the tolerance of a relatively high mean absorbed dose to the liver parenchyma from β-particles. Keywords: Radioembolisation; Y-90; SIR; Surgery; Activity heterogeneity
|
|
| 28. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity
- 2015
-
Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused 90Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. Methods A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-μm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a 90Y-dose point kernel to the microsphere distributions. Results A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5–1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. Conclusions Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.
|
|
| 29. |
- Högberg, Jonas, 1976, et al.
(författare)
-
On the dose heterogeneity in normal liver tissue due to treatment of liver tumors with yttrium-90 microspheres
- 2012
-
Ingår i: 25th Annual Congress on European Association of Nuclear Medicine, Milano, Italy, October 27-31, 2012. European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:suppl 2
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: When treating patients with primary or metastatic liver cancer, applying external radiotherapy, an absorbed dose of 30 - 35 Gy to the whole normal liver tissue volume is associated with a 5 % risk of radiation-induced hepatitis. If less than half of the normal liver volume is being exposed, the threshold for a 5 % risk of hepatitis is increased to above 60 Gy for both primary and metastatic liver cancer. Experience with patients treated with SIR-Spheres® (Sirtex Medical Ltd.), resin microspheres aggregated with yttrium-90, has shown that most patients tolerate an average absorbed dose to normal liver tissue higher than 60 Gy. The high tolerance for this treatment procedure can probably be explained by the resulting heterogenic distribution of radioactivity. It is of interest to study the degree of heterogeneity in the distribution of radioactivity in normal liver tissue, in order to explain or even predict the tolerance to radiation. The aim of this study was to describe the degree of heterogeneity by comparing the relative standard deviations of the radioactivity concentration for different sample mass categories. Materials and Methods: Two patients with cholangiocarcinoma were planned for a combined treatment with yttrium-90-aggregated SIR-Spheres followed by surgery 9 days after radiotherapy. According to standard protocol for treatments with SIR-Spheres, the therapies were preceded by Tc-99m-labled Macro aggregated albumin (Tc-99m-MAA) distribution studies for pre-therapeutic dosimetry and lung shunting evaluations. After surgery the resected tissue, containing both tumour and normal tissue, was studied regarding the distribution of radioactivity. Several small circular samples of normal liver tissue were punched out from 2 mm thick slices of resected tissue, deliberately varying the sizes, and thus the masses of the tissue samples (from 6 to 102 mg). The samples were weighed and categorized in two (first patient) and three (second patient) groups, depending on sample mass. After this the radioactivity was measured with a NaI(Tl) detector. The relative standard deviations (SD/Median) for the radioactivity concentration for each sample mass group were determined and compared. Results: The relative standard deviation for the radioactivity concentration was decreasing rapidly with increasing sample mass. Conclusion: The results indicate a considerable degree of heterogeneity in the distribution of microspheres. One probable explanation for this heterogeneity is clustering of microspheres in the blood vessels.
|
|
| 30. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Radiation exposure during liver surgery after treatment with (90)Y microspheres, evaluated with computer simulations and dosimeter measurements.
- 2012
-
Ingår i: Journal of radiological protection : official journal of the Society for Radiological Protection. - : IOP Publishing. - 1361-6498. ; 32:4, s. 439-46
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose. Two patients with liver tumours were planned for a combined treatment, including surgery with preceding injections of β(-) radiation emitting (90)Y microspheres (SIRTEX(®)). The aim of this paper is to present a method of pre-surgical computer simulations of the absorbed dose rate on the surface of tumour tissue, combined with measurements of the actual absorbed dose rate on resected tissue, in order to estimate the absorbed dose to a surgeon's fingers during such surgery procedures. Methods and Materials. The dose rates from β(-) radiation on the surface of tumour tissue were simulated with the software VARSKIN(®)Mod2. The activity concentrations in tumours were estimated, based on SPECT/CT distribution studies of (99m)Tc-MAA and confirmed by SPECT/CT bremsstrahlung studies of (90)Y microspheres. The activity distributions were considered as homogeneous within the tumour regions. The absorbed dose rates at different tumour tissue spots were calculated based on measurements with thermo-luminescent dosimeters (TLD) fastened on resected tissue. Results. The simulations showed a good agreement with the averaged absorbed dose rates based on TLD measurements performed on resected tissue, differing by 13% and 4% respectively. The absorbed dose rates at the measured maximum hotspots were twice as high as the average dose rates for both patients. Conclusion. The data is not sufficient in order to draw any general conclusions about dose rates on tumour tissue during similar surgeries, neither about the influence of dose rate heterogeneities nor about average dose rates. However, the agreement between simulations and measurements on these limited data indicate that this approach is a promising method for estimations of the radiation exposure to the surgeons' fingers during this kind of surgery procedure. More data from similar surgeries are necessary in order to validate the method.
|
|
| 31. |
- Klintö, Kristina, et al.
(författare)
-
Coverage, reporting degree and design of the Swedish quality registry for patients born with cleft lip and/or palate
- 2020
-
Ingår i: BMC Health Services Research. - : BMJ Publishing Group Ltd. - 1472-6963. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The objective of the Swedish cleft lip and palate (CLP) registry is to promote quality control, research and improvement of treatment, by comparison of the long-term results of surgery, orthodontics and speech from all six Swedish CLP centres. The purpose of the study was to investigate the coverage and reporting degree of the Swedish CLP registry, and to describe the design of the registry and discuss questions of reliability and validity of the data included.Methods: All six Swedish CLP centres participate in the registry. All children in Sweden with cleft lip and/or cleft palate, born from 2009 onwards, are included in the registry. Baseline data such as cleft type (ICD-10 diagnosis), heredity, birth weight and additional deformities and/or syndromes, as well as pre-surgical treatment, are recorded at first visit. Data on surgical treatment are recorded continuously. Treatment outcome regarding dentofacial development and speech are recorded at follow-ups at 5, 10, 16 and 19 years of age. Data on dentofacial development are also recorded 1 year after orthognathic surgery. In addition, data on babbling and speech are recorded at 18 months of age. Coverage degree and reporting degree of surgery was assessed by comparison with registrations in the Swedish Central patient registry. Reporting degree of orthodontic and speech registrations at 5 years of age was assessed by comparison with registrations at baseline.Results: The average coverage degree for children born 2009 to 2018 was 95.1%. For cleft-related surgeries, the average reporting degree was 92.4%. Average reporting degree of orthodontic registrations and speech registrations at age 5 years was 92 and 97.5% respectively.Conclusion: In order to achieve valid and reliable data in a healthcare quality registry, the degree of coverage and reporting needs to be high, the variables included should be limited and checked for reliability, and the professionals must calibrate themselves regularly. The Swedish CLP registry fulfils these requirements.
|
|
| 32. |
- Lindner, P., et al.
(författare)
-
Combined treatment with histamine dihydrochloride, interleukin-2 and interferon-alpha in patients with metastatic melanoma
- 2004
-
Ingår i: Anticancer Res. - 0250-7005. ; 24:3b, s. 1837-42
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Histamine inhibits phagocyte-derived production of reactive oxygen species and improves the anti-tumour efficiency of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) in vitro and in tumour-bearing animals. PATIENTS AND METHODS: In a phase-II study, twenty-seven patients with stage IV melanoma received subcutanous injections of histamine dihydrochloride (histamine) 1.0 mg and IL-2 2.4 MIU/m2 twice daily (BID) days 1-5 and 8-12. IFN-alpha 3 MIU once daily was administered throughout a cycle (days 1-28; n=14). Alternatively, bolus doses of IL-2 10 MIU/m2 BID days 1 and 2 and histamine days 1-28 (n=13) were administered. The aim was to study efficiency (survival and tumour response), toxicity and histamine pharmacokinetics. RESULTS: The median survival time was 11.3 (2.5-45) months. One patient achieved a complete response and 3 patients had partial responses. The compounds were safely self-administered with low toxicity. Plasma histamine concentrations significantly increased after an injection of histamine over 10 minutes (3 +/- 1 vs. 63 +/- 27 nmol/l). CONCLUSION: Histamine, IL-2 and IFN-alpha treatment is safe, well-tolerated and tumour responses were observed. The putative efficiency of histamine as an adjunct to cytokine therapy in metastatic melanoma needs to be confirmed in later randomized trials.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Lindnér, Per, 1956, et al.
(författare)
-
The impact of changed strategies for patients with cholangiocarcinoma in this millenium.
- 2015
-
Ingår i: HPB surgery : a world journal of hepatic, pancreatic and biliary surgery. - : Hindawi Limited. - 0894-8569. ; 2015
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Cholangiocarcinoma is a cancer with a poor prognosis. In this millennium there are new diagnostic and therapeutic strategies for these patients. Aim. The aim of this study was to find if these changes influenced survival of individuals with proximal cholangiocarcinoma. Material. 627 individuals with a diagnosis of cholangiocarcinoma (not including distal common duct cancer) during the period from 2000 to 2011 were registered in Sweden's Western Region. The material was divided into three consecutive time periods. Results. The overall survival curves for individuals with cholangiocarcinoma improved over the three time periods (n = 627)(P = 0.0013). Median survival increased from 2.6 months in the first period (2000-2003) to 3.6 months in the final four years (2008-2011). Patients with perihilar cholangiocarcinoma (PHC) had longer median survival than those with intrahepatic cholangiocarcinoma (IHC): 6.8 versus 3.2 months (P = 0.0003). An improvement in the survival curves over time was seen for those with IHC (P = 0.034) but not for patients with PHC (P = 0.38). Nine percent of the patients with IHC had potential curative surgical therapy. The three-year survival rate after liver resection for patients with IHC was 35% and 60% after liver transplantation. Among patients with PHC, 15.3% had potential curative bile duct resection with a concomitant liver resection and 6.1% bile duct resection alone. The three-year survival rate for these two groups was 32% and 20%, respectively. Conclusion. Overall survival for individuals with PHC was better than for those with IHC. Over time survival in IHC patients improved but not in those with PHC.
|
|
| 36. |
|
|
| 37. |
- Olofsson Bagge, Roger, et al.
(författare)
-
Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases : A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)
- 2023
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 41:16, s. 3042-3050
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.METHODS: In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.RESULTS: Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.CONCLUSION: IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
|
|
| 38. |
- Olofsson Bagge, Roger, 1978, et al.
(författare)
-
Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)
- 2023
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 41:16, s. 3042-50
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSEAbout half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.METHODSIn this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.RESULTSNinety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.CONCLUSIONIHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
|
|
| 39. |
- Olofsson, Roger, 1978, et al.
(författare)
-
Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
- 2014
-
Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 317-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.
|
|
| 40. |
- Olofsson, Roger, 1978, et al.
(författare)
-
Isolated Hepatic Perfusion for Ocular Melanoma Metastasis: Registry Data Suggests a Survival Benefit.
- 2014
-
Ingår i: Annals of surgical oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 21:2, s. 466-472
-
Tidskriftsartikel (refereegranskat)abstract
- Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 35% of the patients, with the liver being the most common site for metastases. These metastases are generally refractory to systemic chemotherapy, and the median survival for patients with liver metastases is about 6months. This phase II trial reports the experience of isolated hepatic perfusion (IHP) as a treatment option.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Pereira, Maria J, et al.
(författare)
-
mTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes
- 2012
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 355:1, s. 96-105
-
Tidskriftsartikel (refereegranskat)abstract
- Rapamycin is an immunosuppressive agent used after organ transplantation, but its molecular effects on glucose metabolism needs further evaluation. We explored rapamycin effects on glucose uptake and insulin signalling proteins in adipocytes obtained via subcutaneous (n=62) and omental (n=10) fat biopsies in human donors. At therapeutic concentration (0.01 μM) rapamycin reduced basal and insulin-stimulated glucose uptake by 20-30%, after short-term (15 min) or long-term (20 h) culture of subcutaneous (n=23 and n=10) and omental adipocytes (n=6 and n=7). Rapamycin reduced PKB Ser473 and AS160 Thr642 phosphorylation, and IRS2 protein levels in subcutaneous adipocytes. Additionally, it reduced mTOR-raptor, mTOR-rictor and mTOR-Sin1 interactions, suggesting decreased mTORC1 and mTORC2 formation. Rapamycin also reduced IR Tyr1146 and IRS1 Ser307/Ser616/Ser636 phosphorylation, whereas no effects were observed on the insulin stimulated IRS1-Tyr and TSC2 Thr1462 phosphorylation. This is the first study to show that rapamycin reduces glucose uptake in human adipocytes through impaired insulin signalling and this may contribute to the development of insulin resistance associated with rapamycin therapy.
|
|
| 44. |
- Pereira, Maria J, 1981, et al.
(författare)
-
The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue.
- 2013
-
Ingår i: Molecular and cellular endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 365:2, s. 260-9
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclosporin A (CsA), tacrolimus and rapamycin are immunosuppressive agents (IAs) associated with insulin resistance and dyslipidemia, although their molecular effects on lipid metabolism in adipose tissue are unknown. We explored IAs effects on lipolysis, lipid storage and expression of genes involved on lipid metabolism in isolated human adipocytes and/or adipose tissue obtained via subcutaneous and omental fat biopsies. CsA, tacrolimus and rapamycin increased isoproterenol-stimulated lipolysis and inhibited lipid storage by 20-35% and enhanced isoproterenol-stimulated hormone-sensitive lipase Ser552 phosphorylation. Rapamycin also increased basal lipolysis (∼20%) and impaired insulin's antilipolytic effect. Rapamycin, down-regulated the gene expression of perilipin, sterol regulatory element-binding protein 1 (SREBP1) and lipin 1, while tacrolimus down-regulated CD36 and aP2 gene expression. All three IAs increased IL-6 gene expression and secretion, but not expression and secretion of TNF-α or adiponectin. These findings suggest that CsA, tacrolimus and rapamycin enhance lipolysis, inhibit lipid storage and expression of lipogenic genes in adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.
|
|
| 45. |
- Rizell, Magnus, 1963, et al.
(författare)
-
Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer.
- 2008
-
Ingår i: International journal of clinical oncology / Japan Society of Clinical Oncology. - : Springer Science and Business Media LLC. - 1341-9625. ; 13:1, s. 66-70
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hepatocellular cancer (HCC), as well as cholangiocellular cancer (CCC), has an extremely poor prognosis due to the extent of tumor at diagnosis and the underlying liver disease. Sirolimus is used in the transplantation setting as an immunosuppressive agent, but it also possesses antiproliferative and antiangiogenic properties. The objective of the study was to evaluate the effect of sirolimus on HCC and CCC. METHODS: In a prospective single-arm protocol, the tumor response to sirolimus as the primary endpoint was studied in 21 patients with advanced HCC and nine with CCC. Sirolimus was administered once daily by mouth, with the dose adjusted to a serum trough level between 4 and 15 mug/ml. Tumor response was evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), according to the Response Evaluation Criteria in Solid Tumors (RECIST), every third month. Secondary measures were overall survival, time to tumor progression, tumor markers, and side effects. RESULTS: Of the patients with HCC, one had partial remission (PR) and fi ve patients had stable disease (SD) at 3 months. Of the patients with CCC, three had SD. The median survival for patients with HCC was 6.5 months (range, 0.2-36 months) and that for patients with CCC was 7 months (range, 2.6-35 months). CONCLUSION: Treatment of HCC and CCC with sirolimus can induce temporary PD or SD. This pilot study indicates that sirolimus might be a promising drug for this treatment, but further clinical studies elucidating the biological effects are advocated.
|
|
| 46. |
- Rizell, Magnus, 1963, et al.
(författare)
-
Isolated hepatic perfusion for liver metastases of malignant melanoma.
- 2008
-
Ingår i: Melanoma research. - 0960-8931. ; 18:2, s. 120-6
-
Tidskriftsartikel (refereegranskat)abstract
- The objective was to analyze the outcome of three treatment strategies using isolated hyperthermic liver perfusion (IHP) with melphalan for liver metastases of malignant melanoma. It was designed as an exploratory study. The setting was a single-center study in a university hospital. The study was carried out on 27 patients. IHP was used with modifications during three different time periods (IHP I, IHP II and IHP III), in technique and temperature (amount of melphalan: 0.5, 1.0 and 2 mg/kg body weight in the perfusate; 41, 40 and 40 degrees C). Tumor response was estimated according to WHO criteria with computed tomography or MRI. Mortality and morbidity were secondary measures. Six of 11 patients in the IHP I cohort experienced a partial response (PR). In the IHP II cohort, two patients of 11 experienced a complete response and five a PR. In the IHP III cohort, five of five patients experienced a PR. Six postoperative deaths were reported (27%) (three in the IHP I and three in the IHP II series), secondary to liver insufficiency and multiorgan failure. Treatment of liver metastases of malignant melanoma with isolated hyperthermic melphalan perfusion has shown an impressive tumor response rate, which seems to be higher than the response rates reported for other systemic chemotherapy regimens. The maximum tolerated dose for melphalan in the perfusate was surpassed with a 2 mg/kg body weight. By modifying the technique and restricting the allowed tumor burden, the response rate remained high and the mortality was reduced.
|
|
| 47. |
- Rizell, Magnus, 1963, et al.
(författare)
-
Monotherapy with histamine dihydrochloride suppresses in vivo growth of a rat sarcoma in liver and subcutis.
- 2002
-
Ingår i: Anticancer research. - 0250-7005. ; 22:4, s. 1943-8
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of parenterally-administered histamine dihydrochloride (histamine), the role of the histamine H2-receptor and the importance of histamine administration routes on the in vivo growth of a rat Leydig cell sarcoma (LTW) were explored. MATERIALS AND METHODS: Wistar/Furth rats with LTW tumours transplanted into subcutaneous and liver tissue received treatment by daily subcutaneous injections or by an osmotic pump for 10 days. RESULTS: Subcutaneous injections of histamine (0.5 mg/kg) reduced the liver tumour weight by 46+/-8% (p=0.0002) and subcutaneous tumour weight by 41+/-12% (p=0.026) versus animals receiving subcutaneous saline injections. Histamine continuously administered by osmotic pumps at doses of 0.5, 2 and 20 mg/kg/24 hour, did not reduce tumour growth. Ranitidine (50 mg/kg s.c.), inhibited the anti-tumour effect observed by subcutaneous histamine injections. In conclusion, H2-receptor-mediated tumour growth inhibition was accomplished by bolus injections of histamine.
|
|
| 48. |
- Rizell, Magnus, et al.
(författare)
-
Phase 1 Trial With the Cell-Based Immune Primer Ilixadencel, Alone, and Combined With Sorafenib, in Advanced Hepatocellular Carcinoma
- 2019
-
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 9, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence support immunotherapy in hepatocellular carcinoma (HCC). We have shown that intratumoral injections of the immune primer ilixadencel (pro-inflammatory allogeneic dendritic cells) are safe in renal-cell carcinoma. Here, we assessed ilixadencel as a single agent and combined with sorafenib in advanced HCC. Of 17 HCC patients enrolled, 12 patients received ilixadencel at the dose of 10 x 106 cells (six as monotherapy and six in combination with sorafenib), and five received ilixadencel at the dose of 20 x 106 cells as monotherapy. The primary objective was to evaluate tolerability. All patients had at least one adverse event, with 30% of such events considered as treatment-related, with one single treatment-related grade three event. The most common toxicity was grade 1 and 2 fever and chills. Eleven of 15 evaluable patients (73%) showed increased frequency of tumor-specific CD8(+) T cells in peripheral blood. Overall one patient had a partial response (with ilixadencel as monotherapy), and five had stable disease as overall best response per mRECIST. The median time to progression was 5.5 months, and overall survival ranged from 1.6 to 21.4 months. Our study confirms the safety of ilixadencel as single agent or in combination with sorafenib and indicates tumor-specific immunological responses in advanced HCC.
|
|
| 49. |
- Rizell, Magnus, 1963
(författare)
-
Treatment of malignant tumors with histamine. Clinical and experimental studies
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For metastatic melanoma there is no treatment to prolong life. Histamine has in experimental tumors shown tumor inhibiting effects. In vitro, histamine inhibit phagocyte-derived radical oxygen species to protect natural killer and cytotoxic T-lymphocytes. By exposing the tumor milieu to sufficient concentrations of histamine dihydrochloride, tumor rejection might be facilitated. Methods: Microdialysis was used to estimate interstitial histamine concentrations in tumor as well as normal tissues. The Internal Reference Technique was validated for histamine concentration estimates in the rat, and used to study the pharmacokinetics of histamine in tumor and normal tissue. In a rat Leydig cell sarcoma model, the effect of a subcutaneous bolus dose (0.5mg/kg), or continuous (0.5-20 mg/kg/24h) administration of histamine dihydrochloride was explored. Toxicity and efficiency of combined treatment with histamine dihydrochloride, IL-2 and IFN-a was investigated in patients with metastatic melanoma. Pharmacokinetics of subcutaneously administered histamine was explored.Results: Interstitial histamine concentrations in rat liver, subcutis and tumor could be estimated by microdialysis, using the Internal Reference Technique. A bolus dose of histamine dihydrochloride yielded significant differences in interstitial pharmacokinetic parameters. Maximum concentration and AUC were lower in subcutaneous tumor than in liver tumor.Histamine as monotherapy inhibited rat Leydig cell sarcoma growth in liver and subcutis, if administered subcutaneously as a bolus injection, but not as continuous infusion. The antitumor effect was H2-receptor mediated. In melanoma patients, histamine dihydrochloride, IL-2 and IFN-a was safely administered with moderate adverse events and tumor responses were observed. Histamine dihydrochloride injected over ten minutes significantly increased plasma histamine concentration.Conclusions: Interstitial changes in histamine concentration could be followed by microdialysis, with significantly lower exposure to tumors in subcutis than in liver after a histamine bolus injection. In rat, tumor growth was inhibited by a subcutaneous bolus injection but not continuous infusion of histamine. Histamine dihydrochloride could be administered safely to patients with metastatic melanoma.
|
|
| 50. |
- Sand Bown, Lena, et al.
(författare)
-
Vasopressin-induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection.
- 2016
-
Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 60:5, s. 607-615
-
Tidskriftsartikel (refereegranskat)abstract
- To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery.
|
|
