| 1. |
- Benoni, Henrik
(author)
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Cancer after solid organ transplantation : incidence, risk factors, and survival
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Solid organ transplant recipients (OTRs) are at increased risk of cancer compared with the general population, mainly due to post-transplant immunosuppressive treatment. Furthermore, once diagnosed with cancer, OTRs might experience worse cancerspecific and overall survival than non-transplanted cancer patients. Colorectal cancer (CRC), one of the most commonly occurring cancers in the general population, has often been associated with an even higher incidence after organ transplantation. Its relatively high posttransplantation frequency enables epidemiological research with comparatively high statistical power on e.g. differences in cancer characteristics and treatment associated with transplantation. The aims of the present thesis were to estimate relative and absolute (including excess) risks of a wide range of cancers among Nordic kidney transplant recipients (KTRs), compared with the general population (Study I); to investigate differences in cancerspecific survival among OTRs with cancer, compared with non-transplanted cancer patients, for different types of cancer (Study II); and to establish the influence of organ transplantation on various cancer characteristics, as well as on cancer treatment and outcomes, among Swedish CRC patients (Study III). Materials and methods: In Study I, Nordic national patient, cancer, cause of death, kidney, and transplantation registers were used to identify all recipients of a kidney transplant during 1995 through 2011, as well as corresponding patient and donor characteristics possibly associated with cancer risk. Standardized incidence ratios (SIR), cumulative incidence in the presence of competing events, and absolute excess risks of cancer were calculated. Risk factors for cancer were studied using Cox regression. In Study II, the Swedish national cancer register was used to identify all Swedish cancer patients with a first cancer diagnosis during 1992 through 2013. Data on patient, cancer, and cause of death characteristics were obtained through linkage with the national cancer and cause of death registers. Cox regression was used to estimate hazard ratios for cancer-specific and all-cause death, comparing cancer patients with a history of solid organ transplantation to those without. In Study III, the Swedish register linkage database CRCBaSe was used to identify all Swedish CRC patients with a history of solid organ transplantation prior to first CRC. Five non-transplanted CRC patients were matched to each OTR. Logistic and multinomial regression was used to evaluate the impact of transplantation on cancer characteristics and treatment, and Cox regression was used to estimate rates of cancer-specific and all-cause death depending on previous organ transplantation. Results: Among 12,984 Nordic KTRs included in Study I, increased incidence rates (compared with the general population) were found for a wide range of cancers, especially infection-related cancer types such as non-melanoma skin cancer (NMSC), lip, oral and nasal cancers, male and female external genital cancer, and non-Hodgkin lymphoma. However, excluding NMSC, absolute risks were generally higher for non-infection-related cancers (which were often associated with moderately increased rates), such as lung and kidney cancer. Accounting for the competing event of death, the five-year cumulative incidence of cancer was 8%. In Study II, the rate of cancer-specific death was 1.35-fold increased among 2,143 cancer patients with a history of organ transplantation, compared with 946,089 nontransplanted cancer patients. Specifically, lymphoma, malignant melanoma, and urothelial, breast, head/neck, and colorectal cancers were associated with increased cancer-specific death rates among OTRs, compared with non-OTRs. Study III included 99 OTRs and 491 matched non-OTR comparators with CRC. Transplantation history was associated with lower odds of receiving treatment with abdominal surgery, neoadjuvant radiation for rectal cancer, and adjuvant therapy for colon cancer. Cancer-specific and overall survival, as well as disease-free survival, was lower among the OTRs than among the non-OTRs. Conclusions: Nordic KTRs are at increased risk of developing a wide range of cancers posttransplant, both in relative and absolute terms. Once diagnosed with cancer, OTRs with cancer had worse cancer-specific prognosis, both overall and for several specific cancer types, than non-transplanted cancer patients. Among CRC patients, previous transplantation was associated with differences in both treatment and outcomes. These findings should be considered when evaluating Nordic post-transplant cancer screening protocols, and support holding multidisciplinary team conferences, including organ transplant specialists, for posttransplantation cancer care.
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| 2. |
- Benoni, Henrik, et al.
(author)
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Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study
- 2020
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In: Transplant International. - : WILEY. - 0934-0874 .- 1432-2277. ; 33:12, s. 1700-1710
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Journal article (peer-reviewed)abstract
- Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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| 3. |
- Benoni, Henrik, et al.
(author)
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Survival among solid organ transplant recipients diagnosed with cancer compared to nontransplanted cancer patients : A nationwide study
- 2020
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In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 146:3, s. 682-691
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Journal article (peer-reviewed)abstract
- Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer-specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992-2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow-up was 3.1 (range 0-22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24-1.47). Specifically, higher rates of cancer-specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56-40.6), high-grade non-Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90-3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74-4.52) and urothelial (HR: 2.56, 95% CI: 1.65-3.97), breast (HR: 2.12, 95% CI: 1.38-3.25), head/neck (HR: 1.55, 95% CI: 1.02- 2.36) and colorectal (HR: 1.42, 95% CI: 1.07-1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management.
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| 4. |
- Farrokhnia, Nina, et al.
(author)
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Validating the PSOGI classification of peritoneal disease from non-carcinoid epithelial appendiceal neoplasms in the curative and palliative setting : an observational retrospective study
- 2022
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In: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 13:2, s. 859-870
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Journal article (peer-reviewed)abstract
- Background: Few studies on long-term survival have been published since the new updated pseudomyxoma peritonei (PMP) classification was published in 2016. The aim was to investigate long-term survival according to the Peritoneal Surface Oncology Group International (PSOGI) classification and compare prognostic factors. Methods: From Uppsala University Hospital, consecutive patients referred for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from 2004 to 2017 with peritoneal disease from non-carcinoid mucinous epithelial appendiceal neoplasms were included in the study. The peritoneal disease was divided into four groups: mucin only, low-grade mucinous carcinoma peritonei (MCP-1), high-grade (MCP-2), and high-grade with signet ring cells (MCP-3). Survival curves were rendered, and prognostic factors were compared. Results: The study included 223 patients: 36 with mucin only, 112 with MCP-1, 70 with MCP-2, and 5 with MCP-3. Thirty-eight patients had a palliative debulking or open/close procedure. The 5-and 10-year overall survival was 97% and 97% for mucin only, 83% and 70% for MCP-1, 69% and 49% for MCP-2, with no patients still under follow-up after 5 years in the MCP-3 group. In a multivariable analysis, completeness of cytoreduction (CC) score 2-3 and PSOGI class MCP-3 were significantly associated with lower survival. The 5-year overall survival in the palliative setting was 40% vs. 44% (MCP-1 vs. MCP-2, P>0.05) with median survival 51 vs. 53 months, respectively. Conclusions: The PSOGI classification of PMP provides a solid differentiation of prognostic groups after CRS/HIPEC treatment, but not in the palliative setting.
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| 5. |
- Hjortswang, Henrik, et al.
(author)
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Defining Clinical Criteria for Clinical Remission and Disease Activity in Collagenous Colitis
- 2009
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In: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1536-4844 .- 1078-0998. ; 15:12, s. 1875-1881
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Journal article (peer-reviewed)abstract
- Background: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL. Methods: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day. Results: Severity of bowel symptoms had a deleterious impact on patients' HRQOL. Patients with a mean of >= 3 stools/day or a mean of >= 1 watery stool/day had a significantly impaired HRQOL compared to those with <3 stools/day and < 1 watery stool/day. Conclusions: We propose that clinical remission in collagenous colitis is defined as a mean of <3 stools/day and a mean of < 1 watery stool per clay and disease activity to be a daily mean of >= 3 stools or a mean of >= 1 watery stool.
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| 6. |
- Hjortswang, Henrik, et al.
(author)
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Health-related quality of life is impaired in active collagenous colitis
- 2011
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In: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 43:2, s. 102-109
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Journal article (peer-reviewed)abstract
- Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients' health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p < 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population. (C) 2010 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
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| 7. |
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| 8. |
- Vigren, Lina, et al.
(author)
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Celiac disease and other autoimmune diseases in patients with collagenous colitis
- 2013
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 48:8, s. 944-950
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Journal article (peer-reviewed)abstract
- Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjogren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.
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| 9. |
- Vigren, Lina, et al.
(author)
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Is smoking a risk factor for collagenous colitis?
- 2011
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In: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 46:11, s. 1334-1339
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Journal article (peer-reviewed)abstract
- Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohns disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking inmicroscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. Materials and methods. 116 patients (92 women) with median age of 62 years (interquartile range 55-73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. Results. Of the 116 CC patients, 37% were smokers compared with 17% of controls (p andlt; 0.001, odds ratio (OR) 2.95). In the age group 16-44 years, 75% of CC patients were smokers compared with 15% of controls (p andlt; 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers - at 42 years of age (median) compared with 56 years in non-smokers (p andlt; 0.003). Although the proportion with active disease did not differ between smokers and nonsmokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). Conclusions. Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers.
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