The rate of iatrogenic injuries in surgical patients appears resistant to multiple interventions: what can we learn from aviation safety?

BACKGROUND: This project analyses all iatrogenic injuries from our department over the last decade and tracks their rate against several interventions. METHODS: All patients who sustained an iatrogenic injury between 2012 and 2022 were reviewed. RESULTS: A total of 946 iatrogenic injuries occurred in 731 patients. Sixty per cent of these patients were male; the median age was 39 years. Of 946 injuries, 574 (60.7%) occurred during an operation, and 372 (39.3%) were not related to an operation. Of the operative injuries 412 (71.8%) were enteric injuries. Of the 372 non-operative iatrogenic injuries 304 (82%) were due to indwelling devices (ID), and 34 (10%) occurred during flexible endoscopy. Fifty-five per cent of the injuries due to ID were due to central venous catheters (CVC) and urinary catheters (UC). CVC contributed toward 31% of all non-operation related iatrogenic injuries. One in 54 admissions (946/51 178) and one in 47 (574 /27 342) patients undergoing an operation sustained an iatrogenic injury. The annual rate of iatrogenic injuries did not decrease over the decade despite a multifaceted approach to reduce them. Interventions included electronic database development, procedural standardisation, and checklist implementation. CONCLUSION: Despite multiple interventions over a decade, our rate of iatrogenic injury remains constant. Ongoing multifaceted efforts to reduce this rate must focus on engendering a culture of safety at all levels of healthcare if we hope to match the enviable safety record of the aeronautics industry.

Adverse events associated with the use of indwelling devices in surgical patients.

BACKGROUND: Indwelling devices (IDs) are ubiquitous in modern healthcare and may often be associated with morbidity. This paper investigates adverse events related to IDs in surgical patients, which are generally placed into patients either to administer therapy, manage outputs or for specific therapeutic benefit. METHODS: A retrospective electronic database-based assessment of all adverse events relating to IDs was undertaken from December 2012 to August 2021. All events were categorised by device type, event type, and event severity. RESULTS: A total of 11 130 morbidities were captured over the study period. Of those, 2 195 entries pertained to an ID with 2 402 reported adverse events affecting 1 592 patients. Two-thirds occurred in males and injuries occurred in patients age ranging from eight days to 93 years, with an average age of 36 years. The most frequently implicated devices were surgical drains (including intercostal chest drains), accounting for 491 (20.44%) of adverse events. Central venous catheters (CVCs) and intravenous cannulae were involved in 374 (15.57%) and 332 (13.83%) events, respectively. Unplanned removal (346, 13.91%), output not measured (319, 12.82%), injury (314, 12.62%), and blockage (279, 11.21%) were the most common error types. The majority of adverse events were considered minor, however 27 (1.1%) patients experienced organ dysfunction as a result of an ID-related adverse event, and seven (0.3%) died. CONCLUSIONS: Morbidity related to IDs in surgical patients is a relatively frequent occurrence. Standardisation of ID insertion and care, staff education, and improvements in communication have been identified as the most important strategies by which we can limit error-associated morbidity in patients with IDs.

Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging.

Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of the cancer. Since activated T lymphocytes may serve as a hallmark for anticancer responses, we targeted these cells using the radiotracer N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL-2) for positron emission tomography (PET) imaging. Thus, we noninvasively monitored the effects of local tumor irradiation and/or immunization on tumor-infiltrating and systemic activated lymphocytes in tumor-bearing mice. A 10- and 27-fold higher [18F]FB-IL-2 uptake was observed in tumors of mice receiving tumor irradiation alone or in combination with immunization, respectively. This increased uptake was extended to several non-target tissues. Administration of the CXCR4 antagonist AMD3100 reduced tracer uptake by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes upon cancer treatment. In conclusion, [18F]FB-IL-2 PET can serve as a clinical biomarker to monitor treatment-induced infiltration of activated T lymphocytes and, on that basis, may guide cancer immunotherapies.

Continuation of low-molecular-weight heparin treatment for cancer-related venous thromboembolism: a prospective cohort study in daily clinical practice.

Essentials Low-molecular-weight heparin (LMWH) injections for venous thromboembolism (VTE) may be burdensome. Patients with active cancer and confirmed VTE were included to evaluate LMWH continuation. The cumulative incidence of discontinuation was 21% after a median period of 90 days. One out of five patients discontinued LMWH injections because of side effects. SUMMARY: Background Current guidelines recommend low-molecular-weight heparin (LMWH) monotherapy for 3-6 months as the first-line treatment for cancer-associated venous thromboembolism (VTE). However, although daily administration of LMWH injections over a course of several months may be burdensome, the number of patients who stop treatment because of LMWH side-effects is unknown. Objectives To evaluate the continuation rate and complications of daily LMWH injections in patients with cancer-associated VTE. Methods Consecutive patients with active cancer and objectively confirmed symptomatic proximal deep vein thrombosis and/or pulmonary embolism, treated at three Dutch hospitals and one Spanish hospital, were included to evaluate continuation LMWH therapy during LMWH treatment. Patients were excluded when they received other anticoagulants, were lost to follow-up, or experienced a venous catheter-associated thrombosis. Results A total of 372 patients were analyzed during LMWH treatment for a maximum of 180 days. The cumulative incidence of discontinuation was 21% (95% confidence interval [CI] 17-25) after a median period of 90 days (interquartile range 60-120 days). Only female sex was found to be significantly associated with premature LMWH discontinuation (odds ratio 1.6; 95% CI 1.03-2.5). Thirty patients (8.1%) developed recurrent VTE, 30 patients (8.3%) suffered a major bleed, and 106 patients (28%) died. Conclusion Our study reveals that one of five patients with cancer-associated VTE stopped LMWH injections because of side-effects. This finding provides relevant background information for current clinical trials investigating the efficacy and safety of direct oral anticoagulants as compared with LMWH.

Initial evaluation of a canine stifle arthrotomy post-operative pain model.

Most models of acute post-operative orthopedic pain involve the injection of a clinically irrelevant pro-inflammatory agent. The ideal model should, however, be clinically relevant and allow full functional recovery of enrolled animals after research is completed. This study explored the validity of a model employing arthrotomy and objectively measured limb use. Six purpose-bred Beagles underwent arthrotomies on each stifle with a washout period in between. Using a randomized crossover design, each dog received placebo and an extended-release buprenorphine (ER-Bup) preparation. Static and dynamic ground reaction forces (GRFs) were measured prior to and for 72 h following surgery using a pressure sensitive walkway (PSW). GRFs for each hind limb were compared using difference (delta), and symmetry indices (SI). The effects of surgery and of treatment were analyzed using repeated measures ANCOVA. The results indicated significantly decreased limb use compared to baseline for placebo, and significantly increased limb use in the ER-Bup group over placebo at all times for % bodyweight distribution (%BWdistrib), peak vertical force (PVF) and vertical impulse (VI). There was a significant treatment by time interaction for velocity (P = 0.03) and %BWdistrib (P = 0.01, 0.003). Overall, the data show that reduced limb use was present for at least 72 h following arthrotomy. In addition, the use of the ER-Bup analgesic decreased lameness, confirming the validity of this approach as a model of post-operative pain. Subjective assessments did not detect the pain-inducing effects of arthrotomy or pain-alleviating effects of treatment, and subjective measures of procedural pain in research dogs need to be developed.

Rac1 modification by an electrophilic 15-deoxy Δ(12,14)-prostaglandin J2 analog.

Vascular endothelial cells (ECs) are important for maintaining vascular homeostasis. Dysfunction of ECs contributes to cardiovascular diseases, including atherosclerosis, and can impair the healing process during vascular injury. An important mediator of EC response to stress is the GTPase Rac1. Rac1 responds to extracellular signals and is involved in cytoskeletal rearrangement, reactive oxygen species generation and cell cycle progression. Rac1 interacts with effector proteins to elicit EC spreading and formation of cell-to-cell junctions. Rac1 activity has recently been shown to be modulated by glutathiolation or S-nitrosation via an active site cysteine residue. However, it is not known whether other redox signaling compounds can modulate Rac1 activity. An important redox signaling mediator is the electrophilic lipid, 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2). This compound is a downstream product of cyclooxygenase and forms covalent adducts with specific cysteine residues, and induces cellular signaling in a pleiotropic manner. In this study, we demonstrate that a biotin-tagged analog of 15d-PGJ2 (bt-15d-PGJ2) forms an adduct with Rac1 in vitro at the C157 residue, and an additional adduct was detected on the tryptic peptide associated with C178. Rac1 modification in addition to modulation of Rac1 activity by bt-15d-PGJ2 was observed in cultured ECs. In addition, decreased EC migration and cell spreading were observed in response to the electrophile. These results demonstrate for the first time that Rac1 is a target for 15d-PGJ2 in ECs, and suggest that Rac1 modification by electrophiles such as 15d-PGJ2 may alter redox signaling and EC function.

The spectrum and outcome of pregnant trauma patients in a metropolitan trauma service in South Africa.

INTRODUCTION: Pregnant patients involved in trauma pose unique diagnostic and treatment challenges as the physiological and anatomical changes associated with pregnancy, and the need to preserve foetal well-being, result in a number of nuances in the standard resuscitation algorithms. This clinical audit within a busy developing world trauma service describes the spectrum and outcome of pregnant trauma patients. METHODS: All pregnant patients presenting to the Pietermaritzburg Metropolitan Hospital Complex following trauma were included in the study. Data were retrieved from the trauma registry and analyzed using descriptive statistics on a spreadsheet. The study ran from the 1st of July 2011 to the 31st of December 2013. RESULTS: During the study period, 1075 female trauma patients were admitted, with a 4% incidence of pregnant patients (42/1075). The mean age of the patients in the study was 24.9 years with an average age of gestation of 21.4 weeks. Blunt trauma accounted for the majority of injuries (57%). Trauma was by way of intentional assault in 52% of the cases. Of the cases of assault, 81% of the time, the assailant was known to the victim and in the majority of cases (55%) the assailant was the patient's intimate partner. Polytrauma predominated as the most common pattern of injury. Foetal death occurred in more than a third of cases (15/42). In 90% of the patients with an Injury Severity Score greater than fifteen, there was foetal death. Eighty-six percent (6/7) of the patients who required surgery had an unfavourable foetal outcome. In 73% of the cases of foetal death, the pregnancies were less than 28 weeks gestation. CONCLUSION: In an environment with high rates of interpersonal violence, trauma in pregnancy is not an uncommon occurrence. It is most commonly due to assault and the assailant is known to the victim in the majority of cases. Blunt trauma still predominates in this setting but there is a high incidence of penetrating trauma. Foetal mortality in this group is high and reflects the severity of the trauma experienced.

Dose rate calculations for a reconnaissance vehicle.

A Chemical Nuclear Reconnaissance System (CNRS) has been developed by the British Ministry of Defence to make chemical and radiation measurements on contaminated terrain using appropriate sensors and recording equipment installed in a land rover. A research programme is under way to develop and validate a predictive capability to calculate the build-up of contamination on the vehicle, radiation detector performance and dose rates to the occupants of the vehicle. This paper describes the geometric model of the vehicle and the methodology used for calculations of detector response. Calculated dose rates obtained using the MCBEND Monte Carlo radiation transport computer code in adjoint mode are presented. These address the transient response of the detectors as the vehicle passes through a contaminated area. Calculated dose rates were found to agree with the measured data to be within the experimental uncertainties, thus giving confidence in the shielding model of the vehicle and its application to other scenarios.

Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology.

The development of effective strategies against cervical cancer in Africa requires accurate type specific data on human papillomavirus (HPV) prevalence, including determination of DNA sequences in order to maximise local vaccine efficacy. We have investigated cervical HPV infection and squamous intraepithelial lesions (SIL) in an unselected cohort of 1061 women in a rural Gambian community. Squamous intraepithelial lesions was diagnosed using cytology and histology, HPV was typed by PCR-ELISA of DNA extracts, which were also DNA sequenced. The prevalence of cervical HPV infection was 13% and SIL were observed in 7% of subjects. Human papillomavirus-16 was most prevalent and most strongly associated with SIL. Also common were HPV-18, -33, -58 and, notably, -35. Human papillomavirus DNA sequencing revealed HPV-16 samples to be exclusively African type 1 (Af1). Subjects of the Wolof ethnic group had a lower prevalence of HPV infection while subjects aged 25-44 years had a higher prevalence of cervical precancer than older or younger subjects. This first report of HPV prevalence in an unselected, unscreened rural population confirms high rates of SIL and HPV infection in West Africa. This study has implications for the vaccination of Gambian and other African populations in the prevention of cervical cancer.

Mechanisms of NH4+ and NH3 transport during hypokalemia.

Along the collecting duct, secretion of ammonium (NH) is thought to occur through active H+ secretion in parallel with the non-ionic diffusion of ammonia (NH3). Thus NH3 is secreted into the collecting duct lumen down its concentration gradient. Moreover, the low NH permeability and high NH3 permeability observed in collecting duct epithelia minimizes back diffusion of NH. In general, an increase in the NH3 concentration gradient between the interstitium and the collecting duct lumen correlates with increased NH secretion. However, our laboratory and others have shown an important role of direct NH transport by the Na,K-ATPase. As K+ and NH compete for a common extracellular binding site on the Na,K-ATPase, reduced interstitial K+ concentration, such as during hypokalemia, augments NH uptake. Na,K-ATPase-mediated NH uptake provides an important source of H+ for net acid secretion during hypokalemia and contributes to the increase in NH excretion and metabolic alkalosis observed in this treatment model.

Nithsdale Schizophrenia Surveys 24: sexual dysfunction. Case-control study.

BACKGROUND: That sexual dysfunction occurs in schizophrenia is not in doubt. Previous studies have had weaknesses such as the use of selected populations or the absence of a control group. AIMS: To measure rates of sexual dysfunction in people with schizophrenia compared with the general population. METHOD: Sexual dysfunction was assessed by a self-completed gender-specific questionnaire. Ninety-eight (73%) of 135 persons with schizophrenia and 81 (71%) of 114 persons recruited as controls returned the questionnaire. RESULTS: At least one sexual dysfunction was reported by 82% of men and 96% of women with schizophrenia. Male patients reported less desire for sex, were less likely to achieve and maintain an erection, were more likely to ejaculate more quickly and were less satisfied with the intensity of their orgasms. Female patients reported less enjoyment than the control group. Sexual dysfunction in female patients was associated with negative schizophrenic symptoms and general psychopathology. There was no association between sexual dysfunction and type of antipsychotic medication. CONCLUSIONS: People with schizophrenia report much higher rates of sexual dysfunction than do the general population. Men and women with schizophrenia have a different pattern of sexual dysfunction.

De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models.

Acrocallosal syndrome (ACS) is characterised by postaxial polydactyly, hallux duplication, macrocephaly, and absence of the corpus callosum, usually with severe developmental delay. The condition overlaps with Greig cephalopolysyndactyly syndrome (GCPS), an autosomal dominant disorder that results from mutations in the GLI3 gene. Here we report a child with agenesis of the corpus callosum and severe retardation, both cardinal features of ACS and rare in GCPS, who has a mutation in GLI3. Since others have excluded GLI3 in ACS, we suggest that ACS may represent a heterogeneous group of disorders that, in some cases, may result from a mutation in GLI3 and represent a severe, allelic form of GCPS. The finding is important for counselling families with suspected ACS.

Familial external angular dermoid: evidence for a genetic link?

Congenital craniofacial dermoid cysts are hamartomas of ectodermal and mesodermal origin, made up of keratinizing epithelium lining a cavity containing dermal skin appendages. They usually present as an asymptomatic, firm, round mass, usually noticed at birth or in the first year. They are thought to occur as a result of ectodermal sequestration at lines of fusion during embryological development. Although nasal and epibulbar dermoid cysts have occurred in families and have been associated with inheritable gene defects, there has previously been no evidence for a similar etiology in external angular cases. We present the first description of external angular dermoids occurring in siblings suggesting that this subgroup may, in some instances, also have a genetic origin.

A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals.

The human TWIST gene encodes a 202 amino acid transcription factor characterized by a highly conserved basic-helix-loop-helix motif in the C-terminal half, and a less conserved N-terminal half that has binding activity toward the histone acetyltransferase p300. Between these domains is a repeat region of unknown function that encodes the glycine-rich sequence (Gly)5Ala(Gly)5. Heterozygous mutations of TWIST were previously described in Saethre-Chotzen craniosynostosis syndrome [El Ghouzzi et al., 1997; Howard et al., 1997]. During a search for TWIST mutations in patients with craniosynostosis, we identified, in addition to 11 novel and one previously described bona fide mutations, several individuals with rearrangements of the glycine-rich region, involving either deletion of 18 nucleotides or insertion of three, 15, or 21 nucleotides. None of these rearrangements was consistently associated with clinical disease and we conclude that they are at most weakly pathogenic. The glycine stretch may serve as a flexible linker between the functional domains of the TWIST protein, and as such may be subject to reduced evolutionary constraint.

Surgical options for aesthetic enhancement of the neck.

A slender neckline is recognized as an attractive feature of youth. With aging, laxity develops in the skin and subcutaneous tissues that results in blunting of the cervicomental angle. Many surgical options are available to restore definition to the neck region. This article reviews the methods used to evaluate the appearance of the mentocervical area and also outlines the algorithm used by the senior author to surgically enhance its appearance.

Different outcomes for different interventions with different focus!--A cross-country comparison of community interventions in rural Swedish and US populations.

OBJECTIVES: There is a need among healthcare providers to acquire more knowledge about small-scale and low budget community intervention programmes. This paper compares risk factor outcomes in Swedish and US intervention programmes for the prevention of cardiovascular disease (CVD). The aim was to explore how different intervention programme profiles affect outcome. METHODS: Using a quasi-experimental design, trends in risk factors and estimated CVD risk in two intervention areas (Norsjö. Sweden and Otsego-Schoharie County, New York state) are compared with those in reference areas (Northern Sweden region and Herkimer County, New York state) using serial cross-sectional studies and panel studies. RESULTS: The programmes were able to achieve significant changes in CVD risk factors that the local communities recognized as major concerns: changing eating habits in the Swedish population and reducing smoking in the US population. For the Swedish cross-sectional follow-up study cholesterol reduction was 12%, compared to 5% in the reference population (p for trend differences <0.000). The significantly higher estimated CVD risk (as assessed by risk scores) at baseline in the intervention population was below that of the Swedish reference population after 5 years of intervention. The Swedish panel study provided the same results. In the US, both the serial cross-sectional and panel studies showed a > 10% decline in smoking prevalence in the intervention population, while it increased slightly in the reference population. When pooling the serial cross-sectional studies the estimated risk reduction (using the Framingham risk equation) was significantly greater in the intervention populations compared to the reference populations. CONCLUSIONS: The overall pattern of risk reduction is consistent and suggests that the two different models of rural county intervention can contribute to significant risk reduction. The Swedish programme had its greatest effect on reduction of serum cholesterol levels whereas the US programme had its greatest effect on smoking prevention and cessation. These outcomes are consistent with programmatic emphases. Socially less privileged groups in these rural areas benefited as much or more from the interventions as those with greater social resources.

Endoleak after endovascular repair of abdominal aortic aneurysm.

PURPOSE: We sought to assess the role of endovascular techniques in the management of perigraft flow (endoleak) after endovascular repair of an abdominal aortic aneurysm. METHOD: We performed endovascular repair of abdominal aortic aneurysm in 114 patients, using a variety of Gianturco Z-stent-based prostheses. Results were evaluated with contrast-enhanced computed tomography (CT) at 3 days, 3 months, 6 months, 12 months, and every year after the operation. An endoleak that occurred 3 days after operation led to repeat CT scanning at 2 weeks, followed by angiography and attempted endovascular treatment. RESULTS: Endoleak was seen on the first postoperative CT scan in 21 (18%) patients and was still present at 2 weeks in 14 (12%). On the basis of angiographic localization of the inflow, the endoleak was pure type I in 3 cases, pure type II in 9, and mixed-pattern in 2. Of the 5 type I endoleaks, 3 were proximal and 2 were distal. All five resolved after endovascular implantation of additional stent-grafts, stents, and embolization coils. Although inferior mesenteric artery embolization was successful in 6 of 7 cases and lumbar embolization was successful in 4 of 7, only 1 of 11 primary type II endoleaks was shown to be resolved on CT scanning. There were no type III or type IV endoleaks (through the stent-graft). Endoleak was associated with aneurysm dilation two cases. In both cases, the aneurysm diameter stabilized after coil embolization of the inferior mesenteric artery. There were two secondary (delayed) endoleaks; one type I and one type II. The secondary type I endoleak and the associated aneurysm rupture were treated by use of an additional stent-graft. The secondary type II endoleak was not treated. CONCLUSIONS: Type I endoleaks represent a persistent risk of aneurysm rupture and should be treated promptly by endovascular means. Type II leaks are less dangerous and more difficult to treat, but coil embolization of feeding arteries may be warranted when leakage is associated with aneurysm enlargement.

Alkali metal cation-pi interactions observed by using a lariat ether model system.

The Na(+) or K(+) cation-pi interaction has been experimentally probed by using synthetic receptors that comprise diaza-18-crown-6 lariat ethers having ethylene sidearms attached to aromatic pi-donors. The side chains are 2-(3-indolyl)ethyl (7), 2-(3-(1-methyl)indolyl)ethyl (8), 2-(3-(5-methoxy)indolyl)ethyl (9), 2-(4-hydroxyphenyl)ethyl (10), 2-phenylethyl (11), 2-pentafluorophenylethyl (12), and 2-(1-naphthyl)ethyl (13). Solid-state structures are reported for six examples of alkali metal complexes in which the cation is pi-coordinated by phenyl, phenol, or indole. Indole-containing crown, 7, adopts a similar conformation when bound by NaI, KI, KSCN, or KPF(6). In each case, the macroring and both arenes coordinate the cation; the counteranion is excluded from the solvation sphere. NMR measurements in acetone-d(6) solution confirm the observed solid-state conformations of unbound 7 and 7.NaI. In 7.Na(+) and 7.K(+), the pyrrolo, rather than benzo, subunit of indole is the pi-donor for the alkali metal cation. Cation-pi complexes were also observed for 10.KI and11.KI. In these cases, the orientation of the cation on the aromatic ring is in accord with the binding site predicted by computational studies. In contrast to the phenyl case (11) the pentafluorophenyl group of 12 failed to coordinate K(+). Solid-state structures are also reported for 7.NaPF(6), 10.NaI, 11.NaI, 13.KI, 13.KPF(6), and 9.NaI, in which cation-pi complexation is not observed. Steric and electrostatic considerations in the pi-complexation of alkali metal cations by these lariat ethers are thought to account for the observed complexation behavior or lack thereof.

Colorectal neoplasia: performance characteristics of CT colonography for detection in 300 patients.

PURPOSE: To determine the sensitivity and specificity of computed tomographic (CT) colonography for colorectal polyp and cancer detection by using colonoscopy as the reference standard. MATERIALS AND METHODS: Three hundred patients underwent CT colonography followed by standard colonoscopy. Bowel preparation consisted of magnesium citrate and polyethylene glycol. After colonic air insufflation, patients underwent scanning in the supine and prone positions with 3-mm collimation during a single breath hold. The transverse CT images, sagittal and coronal reformations, and three-dimensional endoluminal images were interpreted by two radiologists independently, and then a consensus reading was performed. CT colonographic findings were correlated with standard colonoscopic and histologic findings. RESULTS: The overall sensitivity and specificity of CT colonography for polyp detection were 90.1% (164 of 182) and 72.0% (85 of 118), respectively. By using direct polyp matching, the overall sensitivity was 69.7% (365 of 524). The sensitivity was 90% (74 of 82) for the detection of polyps 10 mm or larger, 80.1% (113 of 141) for polyps 5.0-9.9 mm, and 59.1% (178 of 301) for polyps smaller than 5 mm. The sensitivity was 94% (64 of 68) for the detection of adenomas 10 mm or larger, 82% (72 of 88) for adenomas 5.0-9.9 mm, and 66.9% (95 of 142) for adenomas smaller than 5 mm. CT colonography was used to identify all eight carcinomas. CONCLUSION: CT colonography has excellent sensitivity for the detection of clinically important colorectal polyps and cancer.