Patient Delay in Colorectal Cancer Patients: Associations with Rectal Bleeding and Thoughts about Cancer

Rectal bleeding is considered to be an alarm symptom of colorectal cancer. However, the symptom is seldom reported to the general practitioner and it is often assumed that patients assign the rectal bleeding to benign conditions. The aims of this questionnaire study were to examine whether rectal bleeding was associated with longer patient delays in colorectal cancer patients and whether rectal bleeding was associated with cancer worries. All incident colorectal cancer patients during a 1-year period in the County of Aarhus, Denmark, received a questionnaire. 136 colorectal cancer patients returned the questionnaire (response rate: 42%). Patient delay was assessed as the interval from first symptom to help-seeking and was reported by the patient. Patients with rectal bleeding (N = 81) reported longer patient intervals than patients without rectal bleeding when adjusting for confounders including other symptoms such as pain and changes in bowel habits (HR = 0.43; p = 0.004). Thoughts about cancer were not associated with the patient interval (HR = 1.05; p = 0.887), but more patients with rectal bleeding reported to have been wondering if their symptom(s) could be due to cancer than patients without rectal bleeding (chi² = 15.29; p<0.001). Conclusively, rectal bleeding was associated with long patient delays in colorectal cancer patients although more patients with rectal bleeding reported to have been wondering if their symptom(s) could be due to cancer than patients without rectal bleeding. This suggests that assignment of symptoms to benign conditions is not the only explanation of long patient delays in this patient group and that barriers for timely help-seeking should be examined.     

Thermoluminescence dosimetry of the dose received by scrotum and testes in radiotherapy of rectal cancer,compared to the point doses calculated by 3D-planning software

PurposeRadiation received by the testes in the course of radiotherapy for rectal cancer may cause oligospermia and azospermia. We sought to determine the dose to the scrotum and testes with thermoluminescence dosimetry (TLD), and compare it to the dose calculated by 3D planning software.MethodsThe TLDs were fixed to the scrotum in six points anteriorly and posteriorly in two fractions of radiotherapy. All patients received a 50–50.4 Gy total dose in prone position with 3D-planning. The average dose of TLD measurements was compared to the average of 6 relevant point doses calculated by the planning software.ResultsThe mean scrotal dose of radiation in 33 patients as measured by TLD was 3.77 Gy (7.5% of the total prescribed dose), and the mean of point doses calculated by the planning software was 4.11 Gy (8.1% of the total dose), with no significant difference. A significant relationship was seen between the position of the inferior edge of the fields and the mean scrotal dose (P = .04). Also body mass index (BMI) was inversely related with the scrotal dose (P = .049).ConclusionWe found a dose of about 4 Gy received by the scrotum and testes from a total prescribed dose of 50 Gy in the radiotherapy of rectal carcinoma patients, with TLD measurements confirming testicular dose estimations by the planning software. This dose could be significantly harmful for spermatogenesis. Thus careful attention to the testicular dose in radiotherapy of rectal cancer for men desiring continued fertility is a necessity.     

Colonoscopy for unexplained rectal bleeding.

Two hundred and thirty-nine patients underwent colonoscopy for unexplained rectal bleeding. Local anorectal conditions were excluded by digital and proctosigmoidoscopic examinations and results of barium studies were negative for all patients. A cause for bleeding was found in 95 patients. Thirty-nine had adenomatous polyps, 24 had unrecognised inflammatory bowel disease, and most importantly 23 (10% of series) had carcinomas. Forty patients had diverticular disease, but nine of them were found to have an adenomatous polyp and four a carcinoma. Colonoscopy can contribute positively to the investigation and treatment of unexplained rectal bleeding and may prevent unnecessary laparotomy.     

Retrospective comparison of rectal toxicity between carbon-ion radiotherapy and intensity-modulated radiation therapy based on treatment plan,normal tissue complication probability model,and clinical outcomes in prostate cancer

This retrospective study assessed the treatment planning data and clinical outcomes for 152 prostate cancer patients: 76 consecutive patients treated by carbon-ion radiation therapy and 76 consequtive patients treated by moderate hypo-fractionated intensity-modulated photon radiation therapy. These two modalities were compared using linear quadratic model equivalent doses in 2 Gy per fraction for rectal or rectal wall dose–volume histogram, 3.6 Gy per fraction-converted rectal dose–volume histogram, normal tissue complication probability model, and actual clinical outcomes. Carbon-ion radiation therapy was predicted to have a lower probability of rectal adverse events than intensity-modulated photon radiation therapy based on dose–volume histograms and normal tissue complication probability model. There was no difference in the clinical outcome of rectal adverse events between the two modalities compared in this study.     

Evaluating the predictive value of quantec rectum tolerance dose suggestions on acute rectal toxicity in prostate carcinoma patients treated with IMRT

AimTo investigate the predictive value of convenience of rectum dosimetry with Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) dose limits, maximum rectum dose (Dmax), total rectal volume (TVrectum), rectal volume included in PTV (VrectumPTV) on Grade 2–3 acute rectal toxicity for utilization in clinical practice.BackgroundNumerous previous data have reported frequent acute proctitis after external-beam RT of prostate cancer. Predicting toxicity limited with dose information is inadequate in clinical practice due to comorbidities and medications used.Materials and MethodSixty-four non-metastatic prostate cancer patients treated with IMRT were enrolled. Patients were treated to a total dose of 70–76 Gy. Rectal dose volume histograms (DVH) of all patients were evaluated retrospectively, and a QUANTEC Score between 0 and 5 was calculated for each patient. The correlation between the rectal DVH data, QUANTEC score, TVrectum, VrectumPTV, rectum Dmax and Grade 2–3 rectal toxicity was investigated.ResultsIn the whole group grade 1, 2 and 3 acute rectal toxicities were 25%, 18.8% and 3.1%, respectively. In the DVH data, rectum doses of all patients were under RTOG dose limits. Statistically significant correlation was found between grade 2–3 rectal toxicity and TVrectum (p = 0,043); however. It was not correlated with QUANTEC score, VrectumPTV and Dmax.ConclusionOur results were not able to show any significant correlation between increasing convenience with QUANTEC limits and lower rectal toxicity. Conclusively, new dosimetric definitions are warranted to predict acute rectal toxicity more accurately in prostate cancer patients during IMRT treatment.     

Predictive value of rectal bleeding in screening for rectal and sigmoid polyps.

Overt rectal bleeding is a common symptom of colorectal cancer and polyps but also occurs in apparently healthy people. It is not known how often this represents bleeding from an undiagnosed rectal or sigmoid polyp or cancer. Three hundred and nineteen apparently healthy men aged over 50, selected by random sampling, were interviewed and underwent flexible sigmoidoscopy to at least 30 cm. Polyps of 10 mm or more in diameter were diagnosed in 12, one of whom also had an adenocarcinoma. Rectal bleeding during the previous six months was reported by 48, four of whom were found to have polyps; seven polyps and one cancer were diagnosed among the 271 who reported no rectal bleeding. Rectal bleeding had a specificity of 86%, a sensitivity of 33%, and a positive predictive value of 8% for rectal or sigmoid polyps or cancer. Restricting the analysis to those subjects who regularly inspected their stools did not improve the predictive value. Sigmoidoscopy in apparently healthy subjects with rectal bleeding will not result in the diagnosis of appreciable numbers of rectal and sigmoid polyps or cancers.     

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study

Objectives

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants.

Background

Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood.

Methods

Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection.

Results

34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding.

Conclusions

Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.     

Long-term follow-up results of endorectal balloon-assisted helical tomotherapy for localized prostate cancer patients in the high-risk group of gastrointestinal adverse events

BackgroundEndorectal balloon (ERB) has been shown to reduce rectal radiation dose and late gastrointestinal toxicities in patients with prostate cancer. However, the usefulness of ERBs for patients with prostate cancer whose rectal shape or size is suboptimal has not been investigated. The purpose of this study was to present the long-term follow-up results of ERB-assisted helical tomotherapy for localized prostate cancer patients whose initial radiation treatment planning (RTP) was unacceptable due to suboptimal rectal shape or size.Materials and methodsOf 541 consecutive patients with localized prostate cancer, 10 were included in this study whose RTPs without ERBs did not meet dose constraints due to: 1) Intestinal intrusion, 2) Small rectum; or 3) Unstable rectal shape. We re-planned using ERBs and delivered 76 Gy in 38 fractions, and evaluated the long-term usefulness and safety of ERB-assisted helical tomotherapy.ResultsAt a median follow-up of 109 months, there were no local recurrences of prostate cancer. The overall, cause-specific, and progression-free survivals at 10 years were 90.0%, 100%, and 83%, respectively. Adverse events of grade 3 or higher were not observed during or after ERB-assisted helical tomotherapy.ConclusionsWhen intestinal intrusion, a small rectum, or an unstable rectal shape is an obstacle for administering helical tomotherapy, ERBs might be the solution.     

Association of CYP2C9 gene polymorphism with bleeding as a complication of warfarin therapy

The aim of this study was to determine the association of bleeding as a complication of warfarin therapy with polymorphism of CYP2C9 gene (alleles 1, 2 and 3). The CYP2C9 is the main enzyme for warfarin metabolism. Study included 181 patients receiving warfarin for at least one month. Allele 1 of CYP2C9 gene (in 94.5%) and genotype *1/*1 (57.5%) prevailed. Allele 3 was found in 12.7% patients. Bleeding side-effects occurred in 18 patients (10%). Patients with allele *1 needed significantly higher maintenance warfarin dose (p=0.011). Those with allele *3 had significantly lower maintenance warfarin dose (p=0.005) and higher prothrombin time (PT) at induction (p=0.034). Bleeding occurred significantly more often in those with lower maintenance warfarin dose (p=0.017). Patients with allele *3 had increased risk of bleeding, with marginal significance (p=0.05). Polymorphism of CYP2C9 could determine dose of warfarin therapy and thus it could be related to the risk of bleeding complications. Allele *3 carriers need lower warfarin dose. Therefore, initially reduced warfarin induction dose in allele *3 carriers could avoid more prolonged PT and decrease the risk of bleeding complication.     

Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.     

膀胱及小肠受量对直肠癌术后放疗副反应的影响

目的:探讨直肠癌术后放疗患者膀胱平均受量及直肠受量对放射性膀胱炎及放射性肠炎的影响。方法:收集我院2005年7月至2010年12月收治的直肠癌根治术后给予放疗的患者130例,收集临床因素、病理因素、放疗因素资料,统计放疗后6个月内放射性肠炎、放射性膀胱炎发生情况。结果:放疗因素中,膀胱壁平均照射剂量对放射性肠炎及膀胱炎的发生有显著影响(P0.05),即膀胱壁剂量越高,副反应发生率越大;当膀胱壁平均剂量达到49.12 Gy时,放射性膀胱炎的发生率显著升高。小肠平均剂量控制在50 Gy以下,其值与放射性肠炎的发生无相关性。结论:直肠癌术后放疗患者膀胱壁平均受量控制在49.12 Gy以下,对减少放射性膀胱炎的发生率有意义。     

Bleeding Risk during Treatment of Acute Thrombotic Events with Subcutaneous LMWH Compared to Intravenous Unfractionated Heparin; A Systematic Review

Background

Low Molecular Weight Heparins (LMWH) are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute coronary syndromes (ACS). Major bleeding was the primary end point.

Methods

Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients’ characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model.

Results

Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60–1.04). In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47–1.00).

Conclusion

The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings.     

Association between EBRT dose volume histograms and quality of life in prostate cancer patients

Aim

To evaluate the association between dose–volume histogram (DVH) values in organs at risk (OAR) and patient-reported HRQoL outcomes.

Colonoscopic polypectomy in children.

Five children presenting with chronic and intermittent rectal bleeding were diagnosed as having colorectal polyps by fibreoptic colonoscopy performed under sedation. Three of the children had had barium-enema films reported on as normal. Eight polyps were seen, of which six were proximal to the sigmoid colon. All were removed endoscopically (one by proctoscopy, one by snare-intussusception) without complication. Colonoscopic polypectomy is a safe and efficient procedure in children, and colonoscopy may be regarded as first-line management in those with rectal bleeding.     

Prostaglandin synthesis inhibitors in ulcerative colitis: Flurbiprofen compared with conventional treatment

It has been suggested that prostaglandins (PGs) play a pathogenetic role in ulcerative colitis (UC) and that treatment with inhibitors of PG synthesis might be of therapeutic benefit. We therefore performed a one-week open trial to compare the effects of oral flurbiprofen with those of conventional therapy with corticosteroids and sulphasalazine, in two groups of patients with active UC. Mean rectal mucosal release of PGE₂, measured by in vivo rectal dialysis, fell by 44% (P< 0.05) after one week's conventional treatment, and the effect of flurbiprofen was not significantly different. However, the patients given flurbiprofen fared significantly worse than those given conventional therapy in respect of rectal mucosal appearance at sigmoidoscopy (P=0.01), rectal electrical potential difference (P< 0.01), rectal mucosal sodium absorption (P=0.01) and rectal bleeding (P< 0.05). Furthermore, flurbiprofen-treated patients showed significant deteriorations in rectal potential difference (P< 0.05) and sodium absorption (P< 0.05). These results do not support the hypothesis that increased mucosal PG production is of major pathogenetic importance in active UC, and suggest that flurbiprofen is unlikely to prove a useful alternative to conventional therapy.     

Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study

BackgroundThe diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD).Methods and findingsUsing data from The Health Improvement Network (THIN) in the United Kingdom (2000–2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age–sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes.ConclusionsBased on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.

Annie Herbert and co-workers study possible relevance of common abdominal symptoms for specialist referral in UK primary care.     

Heightened NTPDase-1/CD39 expression and angiogenesis in radiation proctitis

Radiation proctitis is an inflammatory process associated with persistent and refractory lower gastrointestinal bleeding. Purinergic signaling regulates hemostasis, inflammation, and angiogenesis. For example, CD39, the vascular ectonucleotidase, blocks platelet activation and is required for angiogenesis. Whether CD39 expression is affected by radiation injury is unknown. The aim of this work was to study CD39 expression patterns after clinical radiation injury to the rectum. We prospectively enrolled eight patients with radiation proctitis and five gender-matched controls. Biopsies were taken from normal-appearing rectal mucosa of controls and from the normal sigmoid and abnormal rectum of patients. Expression patterns of CD39, P2Y2 receptor, CD31, CD61 integrin, and vascular endothelial growth factor receptor 2 were examined by immunostaining; levels of CD39 were further evaluated by Western blots. Chronic inflammatory lesions of radiation proctitis were associated with heightened levels of angiogenesis. Immunohistochemical stains showed increased vascular expression of CD39, as confirmed by Western blots. CD39 was co-localized with vascular endothelial markers CD31 and CD61 integrin, as well as expressed by stromal tissues. Development of neovasculature and associated CD39 expression in radiation proctitis may be associated with the chronic, refractory bleeding observed in this condition.     

Lack of Prophylactic Efficacy of Oral Maraviroc in Macaques despite High Drug Concentrations in Rectal Tissues

Maraviroc (MVC) is a potent CCR5 coreceptor antagonist that is in clinical testing for daily oral pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model consisting of weekly SHIV_162p3 exposures to evaluate the efficacy of oral MVC in preventing rectal SHIV transmission. MVC dosing was informed by the pharmacokinetic profile seen in blood and rectal tissues and consisted of a human-equivalent dose given 24 h before virus exposure, followed by a booster postexposure dose. In rectal secretions, MVC peaked at 24 h (10,242 ng/ml) with concentrations at 48 h that were about 40 times those required to block SHIV infection of peripheral blood mononuclear cells (PBMCs) in vitro. Median MVC concentrations in rectal tissues at 24 h (1,404 ng/g) were 30 and 10 times those achieved in vaginal or lymphoid tissues, respectively. MVC significantly reduced macrophage inflammatory protein 1β-induced CCR5 internalization in rectal mononuclear cells, an indication of efficient binding to CCR5 in rectal lymphocytes. The half-life of CCR5-bound MVC in PBMCs was 2.6 days. Despite this favorable profile, 5/6 treated macaques were infected during five rectal SHIV exposures as were 3/4 controls. MVC treatment was associated with a significant increase in the percentage of CD3⁺/CCR5⁺ cells in blood. We show that high and durable MVC concentrations in rectal tissues are not sufficient to prevent SHIV infection in macaques. The increases in CD3⁺/CCR5⁺ cells seen during MVC treatment point to unique immunological effects of CCR5 inhibition by MVC. The implications of these immunological effects on PrEP with MVC require further evaluation.     

Benoxaprofen in the treatment of active ulcerative colitis

We have conducted an open pilot trial to assess the therapeutic effect of the lipoxygenase inhibitor, benoxaprofen, in 10 patients with active ulcerative proctocolitis. After 18 days treatment with benoxaprofen (600 mg daily) there was no significant change in bowel habit, rectal bleeding, constitutional upset, sigmoidoscopic appearance, mucosal histology, haemoglobin, ESR, serum albumin or serumorosomucoid. Benoxaprofen itself seems unlikely to prove useful in ulcerative colitis, but evaluation of the therapeutic potential of other lipoxygenase inhibitors in inflammatory bowel disease may be worthwhile.