Cancer after solid organ transplantation : incidence, risk factors, and survival

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

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study

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.Peer reviewe

Validating the PSOGI classification of peritoneal disease from non-carcinoid epithelial appendiceal neoplasms in the curative and palliative setting : an observational retrospective study

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

Defining Clinical Criteria for Clinical Remission and Disease Activity in Collagenous Colitis

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 or a mean of >= 1 watery stool

Is smoking a risk factor for collagenous colitis?

Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohn's disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking in microscopic 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 < 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 < 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 < 0.003). Although the proportion with active disease did not differ between smokers and non-smokers, 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