Risk of colorectal advanced neoplasia in patients with acute diverticulitis with and without previous colonoscopy

Background and Aim

Guidelines recommend a colonoscopy after an episode of complicated diverticulitis and after a first episode of uncomplicated diverticulitis. The influence of a previous colonoscopy on postdiverticulitis colonoscopic findings has not been studied. The aim of this work was to examine the incidence of adenoma detection rate (ADR), advanced adenoma (AA) and colorectal cancer (CRC) in patients with diverticulitis with and without previous colonoscopy.

Method

This was a retrospective case–control study of subjects with acute diverticulitis. Subsequent and previous colonoscopies were abstracted for ADR, AA and CRC diagnoses. The incidence of neoplasia was compared between patients with and without previous colonoscopy and also with that of a screening population.

Results

Compared with a healthy control group (n = 975), diverticulitis patients without prior colonoscopy (n = 325) had a significantly higher ADR (26.8% vs. 20.5%, p = 0.019) and invasive CRC rate (0.9% vs. 0%, p = 0.016). Risk factors for advanced neoplasia included age ≥ 70 years and complicated diverticulitis. Among subjects with diverticulitis and previous colonoscopy (n = 124), only one patient developed AA and there were no cancer cases.

Conclusions

A previous normal colonoscopy within 5 years before diverticulitis probably overshadows other risk factors for findings of advanced neoplasia and should be considered in the decision to repeat a colonoscopy.     

Screening colonoscopy and detection of neoplasia in asymptomatic,average‐risk,solid organ transplant recipients: case–control study

The aim of this study was to evaluate the detection of colonic neoplasia in an average‐risk population of SOT recipients. Studies regarding colonic neoplasia in solid organ transplantation (SOT) recipients have demonstrated mixed results due to the inclusion of above average‐risk patients. We performed a case–control study of 102 average‐risk SOT recipients who underwent screening colonoscopy, compared with an average‐risk, age and sex‐matched control group (n = 287). Cancer rates were compared with an age‐matched cohort from the National Cancer Institute’s Survival, Epidemiology, and End Results (SEER) database. There was no difference in number of patients with adenomas (P = 1.00). There was no difference in polyps per patient (P = 0.31). Although the number of advanced lesions (excluding adenocarcinoma) between groups did not differ (P = 0.25), there were two adenocarcinomas identified in the SOT group and none in the control group (P = 0.068). Detection of colorectal cancer was an unexpected finding in the SOT cohort and was more likely when compared to age‐matched cancer incidence generated by the SEER database. These results suggest no increased adenoma detection in SOT recipients, but with more cases of colorectal cancer than anticipated. Given previous, larger, transplant database studies demonstrating increased colorectal cancer rates, more frequent screening may be justified.     

实体器官移植受者移植术后下消化道并发症流行病学及影响因素

实体器官移植(SOT)作为治疗终末期器官衰竭疾病的有效手段,临床开展越来越广泛。随着外科手术技术及术后管理水平的逐年提高及新型免疫抑制剂的应用,SOT受者术后生存率和生存质量不断提高。国外研究发现,SOT受者术后下消化道并发症(如憩室炎、结肠息肉和结直肠癌等)发生率随术后时间延长逐年增加,并成为影响受者生存时间和生存质量的重要因素。但目前国内这方面研究较少,且大多为个案报道。本文旨在对近年来SOT受者移植术后下消化道并发症流行病学及其影响因素相关研究进行综述,以期为临床预防及早期诊治提供依据,改善受者预后。     

Risk of lip cancer after solid organ transplantation in the United States

Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261 500 transplant recipients in the United States. Two hundred thirty‐one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2.01, 95% CI 1.44‐2.82), transplanted organ (0.33, 0.20‐0.57, for liver transplants and 3.07, 1.96‐4.81, for lung transplants, compared with kidney transplants), and racial/ethnic groups other than non‐Hispanic whites (0.09, 0.04‐0.2). In addition, incidence increased with age and during the first 3 years following transplant, and was higher in recipients prescribed cyclosporine/azathioprine maintenance therapy (aIRR 1.79, 95% CI 1.09‐2.93, compared with use of tacrolimus/mycophenolate mofetil) and following a diagnosis of cutaneous squamous cell carcinoma (4.21, 2.69‐0.94). The elevation in lip cancer incidence is consistent with an effect of immunosuppression. Notably, the very strong associations with white race and history of prior skin cancer point to an important role for ultraviolet radiation exposure, and cyclosporine and azathioprine may contribute as photosensitizing or DNA damaging agents.     

Gynecologic cancers and solid organ transplantation

Solid organ transplant (SOT) recipients have an approximately 2‐fold greater risk of developing and dying from a malignancy compared to the general population. Among the gynecologic cancers, including uterine, cervical, vaginal, vulvar, and ovarian, the HPV‐related cancers are known to increase among women posttransplant compared to women in the general population, but less is known about the risk of uterine and ovarian cancers. This review provides an overview of the epidemiology of gynecologic cancers after solid organ transplantation, as well as the pathophysiology, management, and specific risk factors associated with these cancers. Closer surveillance for cervical cancers is warranted and larger studies are needed to assess whether and how uterine and ovarian cancers are associated with excess incidence and mortality. Such studies may lead to improvements in screening, prevention, and treatment before and after transplantation.     

Colonoscopy in adult patients: A review of its indications and its yield in detecting colorectal neoplasia

Objective: To review the yield and indications of colonoscopy in a surgical unit at the Prince of Wales Hospital, the result of which may help to select future patients for colonoscopy. Method: The records of 869 patients undergoing elective colonoscopy at the Prince of Wales Hospital within an 18‐month period were reviewed retrospectively. Exclusion criteria included the following: a personal history of colorectal malignancy or polyps, tumours or polyps detectable on rectal examination or rigid sigmoidoscopy, a positive physical examination suggestive of gastrointestinal malignancies, anaemia or positive faecal occult blood. Results: Per rectal bleeding was the most common indication for colonoscopy. Complete colonoscopy rate was 93.7% and abnormalities were reported in 338 patients. Forty‐three patients were found to have cancer whereby age, duration of symptoms, blood mixed with stool and abdominal pain were identified as independent predictive factors. Neoplastic polyps were confirmed in 200 patients. Old age and being male were the only factors predictive of neoplastic polyps. Conclusion: Although the majority of patients present with typical haemorrhoidal bleeding, colonoscopy should be considered seriously for elderly patients, especially those who are male. Chinese Abstract

Figure Chinese Abstract Open in figure viewer PowerPoint

Citing Literature

Volume 6 , Issue 2 May 2002

Pages 48-52     

Effectiveness of a colonoscopic screening programme in first‐degree relatives of patients with colorectal cancer

Aim The study aimed to assess the diagnostic yield of a colonoscopy screening programme in first‐degree relatives of colorectal cancer (CRC) patients and to identify factors associated with advanced neoplasia. Method We conducted a cross‐sectional study. Individual characteristics, family trees and colonoscopy findings of asymptomatic first‐degree relatives of CRC patients were collected. The findings were classified into cancer (invasive carcinoma and/or non‐invasive high‐grade neoplasia), high‐risk adenomas (≥ 10 mm and/or a villous component) and low‐risk adenomas (tubular < 10 mm). The dependent variable was the presence of advanced neoplasia, defined as cancer and/or high‐risk adenoma. Results Two hundred and sixty‐three relatives (147 females), 50.0 ± 11.5 (range, 25–75) years of age, agreed to participate out of a total of 618 who were invited (acceptance rate 42.5%). Index cases were diagnosed at 63.8 ± 12.4 (range, 37–88) years of age. The closest familial relationship was parent/offspring in 168 (63.9%) participants and sibling in 95 (36.1%) participants; 14.8% had three or more relatives with CRC/cancer associated with Lynch syndrome, and two or more affected generations were identified in 24.0%. Advanced neoplasia was found in 56 (21.3%) participants. Of these, invasive cancer, non‐invasive high‐grade neoplasia and high‐risk adenomas were detected in five (1.9%), six (2.3%) and 45 (17.1%) participants, respectively. Low‐risk adenomas were detected in 20 (7.6%) participants. Male sex (odds ratio, 2.59; P = 0.003) and sibling relationship (odds ratio, 2.74; P = 0.001) were independently associated with advanced neoplasia. Conclusion We detected advanced neoplasia in a considerable number of participants. Our data support colonoscopy screening in first‐degree relatives of patients with CRC at an earlier age than in the medium‐risk population. Male sex and sibling relationship were predictors of advanced neoplasia.     

Neurologic complications after solid organ transplantation

Neurologic complications are common after solid organ transplantation and are associated with significant morbidity. Approximately one-third of transplant recipients experiences neurologic alterations with incidence ranging from 10% to 59%. The complications can be divided into such of those common to all types of transplant and others of those specific to transplanted organ. The most common complication seen with all types of transplanted organ is neurotoxicity attributable to immunosuppressive drugs, followed by seizures, opportunistic central nervous system (CNS) infections, cardiovascular events, encephalopathy and de novo CNS neoplasms. Amongst immunosuppressants, calcineurin inhibitors are the main drugs involved in neurotoxicity, leading to complications which ranges from mild symptoms, such as tremors and paresthesia to severe symptoms, such as disabling pain syndrome and leukoencephalopathy. Neurologic complications of liver transplantation are more common than that of other solid organ transplants (13–47%); encephalopathy is the most common CNS complication, followed by seizures; however, central pontine myelinolysis can appear in 1–8% of the patients leading to permanent disabilities or death. In kidney transplanted patients, stroke is the most common neurologic complication, whereas cerebral infarction and bleeding are more typical after heart transplantation. Metabolic, electrolyte and infectious anomalies represent common risk factors; however, identification of specific causes and early diagnosis are still difficult, because of patient's poor clinical status and concomitant systemic and metabolic disorders, which may obscure symptoms.     

Ischemic preconditioning in solid organ transplantation: from experimental to clinics

This study reviews the current understanding of ischemic preconditioning (IP) in experimental and clinical setting, and the mechanisms that mediate the complex processes involved as a tool to protect against ischemia and reperfusion (I/R) injury, but is not intended as a complete literature review of preconditioning. IP has been mainly elucidated in cardiac ischemia. Recent reports confirm the efficacy of pre- and postconditioning in cardiac surgery and percutaneous coronary interventions in humans. IP utilizes endogenous as well as distant mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. Specifically, preconditioned tissues exhibit altered energy metabolism, better electrolyte homeostasis and genetic reorganization, as well as less oxygen-free radicals and activated neutrophils release, reduced apoptosis and better microcirculatory perfusion. To date, there are few human studies, but recent trials suggest that human liver, lung and skeletal muscle acquire protection after IP. Present data address the potential therapeutic application of IP in the prevention of I/R damage specially aimed at clinical transplantation. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena.     

Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study

The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. This retrospective study registered all cases of post‐transplant melanoma in kidney, heart, lung, and liver transplant recipients followed in our specialized post‐transplant Dermatology Clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age‐ and sex‐standardized incidence ratio (SIR) was calculated using a renal transplantation registry. In our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9‐fold increase in prevalence after 2000. Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow‐up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin cancer, the risk of post‐transplant melanoma has considerably increased over the last decade.     

肝移植受者术后结直肠腺瘤性息肉发生情况及危险因素分析

目的  分析肝移植受者术后结直肠腺瘤性息肉（CAP）的发生情况及危险因素。方法  选取肝移植受者77例,并选取同期行结肠镜检查的体检者231例,分析结直肠息肉发生情况及病理检查结果。收集肝移植受者的临床资料,并根据CAP的发生情况,将肝移植受者分为CAP组（28例）和非CAP组（49例）,分析肝移植术后发生CAP的危险因素。结果  肝移植受者和体检者结直肠息肉的5年累积发生率分别为43%和34%,CAP的5年累积发生率分别为29%和23%,差异均无统计学意义（均为P > 0.05）。肝移植受者中,除1例因息肉较多未统计外,其余息肉共计65个,部分受者发现多个息肉。5个体积较小者未送病理,有病理结果的共60个,包括炎性息肉25个,CAP 33个（其中8个伴有低级别上皮内瘤变,3个伴有高级别上皮内瘤变）,高分化腺癌2个。Cox模型分析提示肝移植受者术后服用环孢素是发生CAP的独立危险因素。结论  肝移植术后CAP发生风险略有增高,服用环孢素是肝移植受者术后发生CAP的独立危险因素,应重视肝移植受者术后结肠镜检查。     

Stress and coping in caregivers of patients awaiting solid organ transplantation

Caregivers for patients undergoing solid organ transplantation play an essential role in the process of transplantation. However, little is known about stress and coping among these caregivers. Six hundred and twenty-one primary caregivers of potential candidates for lung (n = 317), liver (n = 147), heart (n = 115), and/or kidney (n = 42) transplantation completed a psychometric test battery at the time of the candidate's initial pre-transplant psychosocial evaluation. Caregivers were generally well adjusted, with only 17% exhibiting clinical symptoms of depression (Beck Depression Inventory-II score >13) and 13% reporting clinical levels of anxiety (State Trait Anxiety Inventory score >48). Greater caregiver burden and negative coping styles were associated with higher levels of depression. Greater objective burden and avoidant coping were associated with higher levels of anxiety. Caregivers evidenced a high degree of socially desirable (i.e., defensive) responding, which may reflect a deliberate effort to minimize fears or worries so as to not jeopardize patients' listing status.     

New directions for induction immunosuppression strategy in solid organ transplantation

Background

Solid organ transplant centers are increasingly using induction immunosuppression strategies. Induction immunosuppression involves the use of intense therapy at the time of transplantation with the goal of preventing acute rejection and ultimately inducing a tolerogenic state. The objective of this review is to examine specialized induction agents currently in clinical use and highlight novel therapeutics on the horizon for induction immunosuppression.

Methods

A literature search using the PubMed and MEDLINE databases identified salient basic science and clinical research articles on induction immunosuppression for solid organ transplantation.

Conclusions

While current induction immunosuppression agents have reduced the incidence of acute rejection, the goal of transplant tolerance has not been realized. Furthermore, the long-term allograft survival rate is not clearly influenced by the practice of induction immunosuppression. New approaches to tolerance induction, such as costimulatory-based therapy, mixed chimerism, and adoptive cellular transfer, hold promise for more effective induction immunosuppression in solid organ transplantation.     

Skin cancer screening after solid organ transplantation: Survey of practices in Canada

Guidelines recommend annual dermatology screening after solid organ transplantation to facilitate early detection of keratinocyte carcinoma (nonmelanoma skin cancer), the most common posttransplant malignancy. There are limited data on adherence levels and barriers to screening. We conducted a cross‐sectional survey of 477 physicians and nurses providing posttransplant care in Canada. The questionnaire asked about skin cancer screening and education practices, including the perceived importance and barriers. Whereas care providers viewed skin cancer screening as important for adult patients (median rating of 10/10, interquartile range 8‐10), only 53% ensured annual screening for white adult transplant recipients. Having a screening policy in place (adjusted odds ratio 6.78, 95% confidence interval 3.12‐14.74) and a dermatologist present at the transplant center (adjusted odds ratio 2.19, 95% confidence interval 1.03‐4.67) were independently associated with higher adherence. Long wait times, lack of specialized transplant dermatologists, long travel distances, and insufficient priority were cited as the most common barriers for access to dermatologic care. Skin cancer education was provided to patients by over three quarters of care providers. Given the self‐reported lack of adherence to annual skin cancer screening, there is need to develop, evaluate, and implement interventions that improve screening rates and skin cancer outcomes.     

Surgical correction of spinal deformities after solid organ transplantation in childhood

A review of the current literature reveals no systematic analyses of the results of surgical correction of spinal deformity after pediatric organ transplantation. We therefore evaluated clinical and radiographic outcomes of spinal deformity correction after solid organ transplantation in childhood and adolescence. All 211 cases of heart, liver, and kidney transplantations performed in children in our country were reviewed. Six patients had undergone surgical correction of spinal deformity at a mean age 14.6 (range 12–17) years. Clinical data of the patients were evaluated. Radiographs of the whole spine were taken preoperatively, immediately after, at 2-year, and final follow-up visits. The Scoliosis Research Society (SRS) questionnaire was completed and a physical examination was performed at the final follow-up visit. The mean follow-up after spinal surgery was 4.9 years (range 2–7.6 years). Four patients developed scoliosis after organ transplantation without any evidence of scoliosis prior to organ transplantation. One patient with congenital scoliosis was operated on after kidney transplantation. One boy had osteoporosis and severe local kyphosis due to vertebral compression fractures. Four patients underwent anterior and posterior surgery, two posterior only. The mean preoperative Cobb angle of the thoracic curve was 54° (range 42–69°) in the patients with scoliosis. The postoperative values were 30° (26–38°) immediately after instrumentation and 39° (34–42°) at the final follow-up visit. The patient with vertebral compression fractures and progressive kyphosis had 70° curve before surgery, 23° immediately after the operation, and 60° at the final check up. The mean total score on the SRS questionnaire was 95.5 (range 90–101). There is a relatively high incidence (2.8%) of spinal deformities needing operative treatment after solid organ transplantation. Possible etiologies for spinal deformities are growth disturbance and muscle weakness due to the basic disease. The other important factors are related to immunosupressive medication, especially glucocorticoids needed after transplantation. Primary correction of these deformities was satisfactory, but during follow-up, a certain amount of recurrence of the curves was evident. Poor bone quality may explain some of the loss of correction.     

Etiology of increased cancer incidence after solid organ transplantation

Over the past decades, there has been an encouraging increase in survival after solid organ transplantation. However, with longer life spans, more transplant recipients are at risk of dying with functioning grafts from illnesses such as cancer and cardiovascular conditions. Malignancy has emerged as an important cause of death in transplant recipients and is expected to become the leading cause of death in transplanted patients within the next decade. While it is known that solid organ transplant recipients have a three to five-fold increased risk of developing cancer compared with the general population, the mechanisms that lead to the observed excess risk in transplant recipients are less clear. This review explores the etiology of the increased cancer incidence in solid organ transplant including the effect of immunosuppressants on immunosurveillance and activation of oncogenic viruses, and carcinogenic effects of these medications; the role of chronic stimulation of the immune system on the development of cancer; and the impact of pre-existing cancer risk factors and factors related to end-stage organ disease on the cancer excess incidence in solid organ transplant recipients.     

Caveats of mesenchymal stem cell therapy in solid organ transplantation

In the past decade, therapeutic use of mesenchymal stem cells (MSCs) has increased dramatically. The weight of existing evidence supports that the short‐term application of MSCs is safe and feasible; however, concerns remain over the possibility of unwanted long‐term effects. One fundamental difference between MSCs and pharmacotherapy is that, once applied, the effects of cell products cannot be easily reversed. Therefore, a carefully considered decision process is indispensable before cell infusion. In addition to unwanted interactions of MSCs with the host immune system, there are concerns that MSCs may promote tumor progression or even give rise to cancer themselves. As animal models and first‐in‐man clinical studies have provided conflicting results, it is challenging to estimate the long‐term risk of individual patients. In addition, most animal models, especially rodents, are ill‐suited to adequately address questions over long‐term side effects. Based on the available evidence, we address the potential pitfalls for the use of MSCs as a therapeutic agent to control alloimmune effects. The aim of this review was not to discourage investigators from clinical studies, but to raise awareness of the intrinsic risks of MSC therapy.     

Liver transplantation for colorectal liver metastases: revisiting the concept

Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1‐ and 5‐year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5‐year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.