Should we inform women about the recognised risks of childbirth?

BACKGROUND: At present in Australia women are not routinely, systematically informed of the risks of childbirth. AIMS: It is hoped this presentation of the perspective of some women who suffer unexpected obstetric complications will encourage change. MATERIALS AND METHODS: The experience of women involved in obstetric medicolegal reports prepared by a colorectal surgeon over ten years is analysed. RESULTS: Twenty women were identified. Sixteen had vaginal deliveries. All 16 suffered third or fourth-degree tears, six developed rectovaginal fistulae, six required stomas and 11 developed faecal incontinence. Of the four women who delivered by caesarean section, there were two post-operative caecal perforations, one unrecognised small bowel enterotomy, and one patient developed sepsis due to an infected haematoma. Seventeen of the 20 women were noted to suffer psychological sequalae. None of the women recollected being warned of the complication they suffered, and there was no record of such warnings in their medical records. CONCLUSION: Informed written 'consent' for natural vaginal delivery is, understandably, a contentious topic. Although learning from medicolegal cases may go against the grain, as medical professionals it is very difficult to ethically justify the status quo, where women are not routinely simply informed of the risks of childbirth. This is not fair. Even if informing women does not decrease the incidence of complications, the women who subsequently suffer these complications may well handle them much better, recognising they could occur.

Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions.

BACKGROUND: Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. METHODS: In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine staining for CD4(+) and CD8(+) antigen-specific T cells. RESULTS: Of 134 participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but not with any CD4(+) T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). CONCLUSIONS: Systemic HPV-16 E6- and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4(+) T-cell responses may be associated with recent HSIL regression. CLINICAL TRIALS REGISTRATION: NCT02007421.

Human papillomavirus (HPV) genotypes in an Australian sample of anal cancers.

Human papillomavirus (HPV) causes most cases of anal cancers. In this study, we analyzed biopsy material from 112 patients with anal cancers in Australia for the presence of HPV DNA by the INNO LiPA HPV genotyping assay. There were 82% (92) males and 18% (20) females. The mean age at diagnosis was significantly (p = 0.006) younger for males (52.5 years) than females (66 years). HIV-infected males were diagnosed at a much earlier mean age (48.2 years) than HIV negative (56.3 years) males (p = 0.05). HPV DNA was detected in 96.4% (108) of cases. HPV type 16 was the commonest, at 75% (81) of samples and being the sole genotype detected in 61% (66). Overall, 79% (85) of cases had at least one genotype targeted by the bivalent HPV (bHPV) vaccine, 90% (97) by the quadrivalent HPV (qHPV) vaccine and 96% (104) by the nonavalent HPV (nHPV) vaccine. The qHPV vaccine, which is now offered to all secondary school students in Australia, may prevent anal cancers in Australia. However, given the mean age of onset of this condition, the vaccine is unlikely to have a significant impact for several decades. Further research is necessary to prove additional protective effects of the nHPV vaccine.

Effectiveness of an Oral Gastrografin Regimen for Complete Distal Intestinal Obstruction Syndrome.

Objectives: To assess the effectiveness of oral Gastrografin treatment and outcomes in adult patients with complete distal intestinal obstruction syndrome (cDIOS). Background: DIOS is an important gastrointestinal complication of cystic fibrosis (CF). Conservative treatment options for cDIOS are largely empirical, and the optimal management remains unclear. Surgery should be reserved for patients who have failed nonoperative treatment or have immediate indications for surgery. Methods: A retrospective single-institution cohort study was undertaken of adults with CF who had undergone lung transplantation and were admitted with an episode of cDIOS between 2004 and 2020. The outcomes of treatment in a high-volume CF transplant center with routine oral Gastrografin-based therapy were assessed. Results: Forty-seven episodes of cDIOS were recorded in 29 (23.3%) of 124 patients who had undergone lung transplantation for CF, and mean age at cDIOS was 30.3 years (SD ±11.2). Mean follow-up post cDIOS was 75.6 months (SD ±45.5). Twelve patients had >1 cDIOS episode. One episode occurred during recovery after transplantation, and 5 patients were readmitted within 30 days posttransplant with cDIOS. A history of previous abdominal surgery was associated with the development of cDIOS (P < 0.001). Oral Gastrografin therapy was used in 95.7% of the episodes, at varying doses. Three patients (7.0%) were resistant to oral Gastrografin treatment, requiring laparotomy. There were no deaths due to DIOS. Conclusions: Oral Gastrografin is effective and safe for the treatment of cDIOS, with low treatment failure rates. It should be considered as a first-line treatment option for patients with CF presenting with complete distal intestinal obstruction.

Anal cancer: a 20-year retrospective study from Australia.

BACKGROUNDS: Anal cancer is an uncommon condition, occurring at higher rates in specific subpopulations. Clinical experience is limited and substantial changes have recently occurred in our understanding of this condition. We, therefore, set out to characterize patients presenting with anal cancer and investigate whether there have been any changes over the past 20 years. METHODS: Retrospective audit of cases identified from pathology and clinical databases during the period 1 January 2000 to 31 December 2019. RESULTS: Two hundred and sixteen patients had anal squamous cell carcinomas, comprising 160 (74%) males and 56 (26%) females. Mean age at initial diagnosis was 55.1 ± 11.20 for males and 60.6 ± 15.18 for females (P = 0.02). At initial diagnosis, HIV-positive cases were significantly younger than HIV negative cases (mean 52.2 ± 9.35 vs. 62.8 ± 11.61, P < 0.001); 46% of cases were classified as intra-anal, 29% perianal and 25% both; 52% were > 2 cm at diagnosis. At presentation, intra-anal cases were larger and more advanced than perianal cases (P = 0.049). Compared with the period 2000-2009, anal cancers presented more commonly in 2010-2019 (148 vs. 76), were more likely to occur in HIV-negative people and to be diagnosed at a similar stage. CONCLUSION: The number of anal cancer cases almost doubled over the study period and people living with HIV presented 10 years younger than others. Perianal cases presented earlier than those originating in intra-anal locations. Together with the large size at diagnosis, this suggests the potential value of screening, particularly for intra-anal cancers in those at high risk.

Quantitative analysis of tissue folate using ultra high-performance liquid chromatography tandem mass spectrometry.

The tissue distribution of folate in its numerous coenzyme forms may influence the development of disease at different sites. For instance, the susceptibility of human colonic mucosa to localized folate deficiency may predispose to the development of colorectal cancer. We report a sensitive and robust ultra high-performance liquid chromatography (UHPLC) tandem mass spectrometry method for quantifying tissue H(4)folate, 5-CH(3)-H(4)folate, 5-CHO-H(4)folate, folic acid, and 5,10-CH(+)-H(4)folate concentration. Human colonic mucosa (20-100mg) was extracted using lipase and conjugase enzyme digestion. Rapid separation of analytes was achieved on a UHPLC 1.9-µm C18 column over 7 min. Accurate quantitation was performed using stable isotopically labeled ((13)C(5)) internal standards. The instrument response was linear over physiological concentrations of tissue folate (R(2)>0.99). Limits of detection and quantitation were less than 20 and 30 fmol on column, respectively, and within- and between-run imprecision values were 6-16%. In colonic mucosal samples from 73 individuals, the average molar distribution of folate coenzymes was 58% 5-CH(3)-H(4)folate, 20% H(4)folate, 18% formyl-H(4)folate (sum of 5-CHO-H(4)folate and 5,10-CH(+)-H(4)folate), and 4% folic acid. This assay would be useful in characterizing folate distribution in human and animal tissues as well as the role of deregulated folate homeostasis on disease pathogenesis.

How often are patients with clinically apparent inguinal hernias referred to a surgeon accompanied with an ultrasound? A prospective multicentre study.

Objectives This study estimated the frequency of ultrasounds ordered for clinically obvious inguinal hernias in patients referred to surgeons and evaluated the clinical value of ultrasonography for this patient population. Methods The present study was a prospective diagnostic and therapeutic impact study conducted in district, rural and tertiary referral hospitals in Sydney, Hawkesbury and Wagga Wagga, Australia. The study included adult patients (≥18 years of age) who had been referred to one of the participating surgeons for an elective inguinal hernia repair. The study determined the proportion of: (1) patients who underwent an inguinal hernia repair for a clinically obvious hernia and also had an ultrasound; (2) ultrasounds ordered by general practitioners (GPs); and (3) these ultrasounds that altered diagnosis and consequent surgical management from the surgeon's perspective. Results In all, 144 participants were included in this study. Of these patients, 134 had a clinically apparent inguinal hernia on physical examination, and 63 of 133 patients (47%; 95% confidence interval (CI) 39-56%) underwent an ultrasound (information was missing for one patient). Overall 68 ultrasounds were ordered, with 63 ordered by GPs. Following the ultrasound, surgeons reported that one patient (1%; 95% CI 0-8 patients) had an altered diagnosis, and five patients (8%; 95% CI 3-17 patients) had altered management. Conclusion This study found that almost one in two patients referred to a surgeon with a clinically obvious inguinal hernia also underwent a groin ultrasound. These studies represent an unnecessary waste of limited healthcare resources and low-value medical care because they rarely affect the final diagnosis or surgical management. What is known about the topic? Inguinal hernias are one of the most common presenting complaints to surgeons in Australia. Currently, there are no accepted Australian guidelines for the diagnosis of inguinal hernias. Ultrasound investigation has been shown to aid diagnosis when there is uncertainty after physical examination. There is increasing concern regarding low-value medical care that contributes to a significant waste of healthcare resources within Australia. The use of ultrasounds for the diagnosis of clinically apparent inguinal hernias is a potential area of concern. What does this paper add? This paper is the first to estimate the frequency of ultrasounds being ordered for clinically apparent inguinal hernias. The study shows that approximately one in two patients who present to surgeons with a clinically obvious inguinal hernia have an ultrasound. GPs were the major referral source for these ultrasounds. Finally, these ultrasounds rarely altered final diagnosis or management for patients who presented to surgeons for definitive management. What are the implications for practitioners? This study confirms that ultrasounds for clinically obvious inguinal hernias represent low-value medical care. Based on the results of this study, it is estimated that the cost to Medicare for unnecessary ultrasounds is approximately A$2.5 million per annum. Although it is beyond the scope of the present study to comment on the reasons for the apparent overinvestigation of ultrasounds for inguinal hernias, the findings suggest that clinical guidelines may help address this problem.

Abdominal wall closure with prophylactic mesh in colorectal operations.

BACKGROUND: Prospective studies demonstrate that over one-third of patients undergoing standard suture closure of laparotomy wounds will develop incisional hernias (IHs). Whilst prophylactic mesh has been demonstrated to decrease IH rates in clean laparotomy wounds, mesh has been associated with high rates of seroma formation (>30%), infection (>10%) and pain, discouraging many surgeons from using mesh, especially combined with intestinal surgery. The aim of this study is to review the experience of a single colorectal surgeon who, after noting high IH rates in his own patients, started placing prophylactic mesh routinely in patients judged to be at high risk of IH. METHODS: The records of all patients undergoing bowel resections and ileostomy closure by one surgeon from 2008 to 2018 were independently retrospectively analysed. RESULTS: Of the 935 procedures identified, 662 patients underwent midline laparotomy with bowel resection and 273 patients underwent closure of loop ileostomy. Mesh was placed prophylactically in 221 (23.6%) of 935 procedures. Comparing the mesh and non-mesh groups, wound infections occurred in nine (4.1%) versus 23 (3.2%) (P = 0.53), seromas occurred in nine (4.1%) versus six (0.8%) (P = 0.003) and chronic pain was noted in 12 (5.4%) versus 17 (2.4%) (P = 0.04). The mean follow-up was 33 months in both the mesh and non-mesh groups. IHs have occurred in three (1.3%) of the mesh group compared to 95 (13.3%) of the non-mesh group procedures (P = 0.0001). CONCLUSION: In colorectal operations, prophylactic mesh decreases the risk of IH without prohibitive complications.

Multimedia article. An improved technique for end stoma creation in obese patients.

PURPOSE: The formation of an end colostomy in obese patients can be technically demanding and often requires the creation of a particularly large defect in the abdominal wall. This is because of the thickness of the subcutaneous fat and mesenteric fat, and increased resistance or friction while negotiating the bowel and mesentry through the abdominal wall. METHODS: The use of an Alexis Wound Protector to circumferentially retract the abdominal wall defect and, thus decrease resistance or friction during stoma formation, is described (see Video, Supplemental Digital Content 1 and 2, which demonstrates the technique, http://links.lww.com/A997 and http://links.lww.com/A998). RESULTS: This technique has been used in eight obese patients who have undergone end stoma formation. In each patient, the efficacy of the wound protector was immediately obvious, resulting in a smaller than usual defect in the abdominal wall and less trauma to the bowel. CONCLUSIONS: The use of a wound protector has decreased the size of the abdominal wall defect necessary for stoma creation in obese patients and hopefully will decrease the risk and rate of parastomal hernia formation.

The place of elective surgery following acute diverticulitis in young patients: when is surgery indicated? An analysis of the literature.

Diverticulitis in the young is often regarded as a specific entity. Resection after a single attack because of a more "virulent" course of the disease has been accepted as conventional wisdom. The evidence for such a recommendation and the place of elective surgery was reviewed by a search of Medline, PubMed, Embase, and the Cochrane library for articles published between January 1965 and March 2008 using the terms diverticular disease and diverticulitis. Publications had to give specific information on at least ten younger patients (age

Epigenetic inactivation of a cluster of genes flanking MLH1 in microsatellite-unstable colorectal cancer.

Biallelic promoter methylation and transcriptional silencing of the MLH1 gene occurs in the majority of sporadic colorectal cancers exhibiting microsatellite instability due to defective DNA mismatch repair. Long-range epigenetic silencing of contiguous genes has been found on chromosome 2q14 in colorectal cancer. We hypothesized that epigenetic silencing of MLH1 could occur on a regional scale affecting additional genes within 3p22, rather than as a focal event. We studied the levels of CpG island methylation and expression of multiple contiguous genes across a 4 Mb segment of 3p22 including MLH1 in microsatellite-unstable and -stable cancers, and their paired normal colonic mucosa. We found concordant CpG island hypermethylation, H3-K9 dimethylation and transcriptional silencing of MLH1 and multiple flanking genes spanning up to 2.4 Mb in microsatellite-unstable colorectal cancers. This region was interspersed with unmethylated genes, which were also transcriptionally repressed. Expression of both methylated and unmethylated genes was reactivated by methyltransferase and histone deacetylase inhibitors in a microsatellite-unstable colorectal carcinoma cell line. Two genes at the telomeric end of the region were also hypermethylated in microsatellite-stable cancers, adenomas, and at low levels in normal colonic mucosa from older individuals. Thus, the cluster of genes flanking MLH1 that was specifically methylated in the microsatellite-unstable group of cancers extended across 1.1 Mb. Our results show that coordinate epigenetic silencing extends across a large chromosomal region encompassing MLH1 in microsatellite-unstable colorectal cancers. Simultaneous epigenetic silencing of this cluster of 3p22 genes may contribute to the development or progression of this type of cancer.

Circumferentially oversewn inverted stapled anastomosis.

BACKGROUND: Leak rates of over 5% following anastomoses between the ileum and colon continue to be reported in large series and are associated with substantial morbidity and with mortality rates of 10-20%. In 1994, we began performing circumferentially oversewn inverted stapled anastomoses in patients undergoing ileo-colic anastomoses or ileostomy closure. It has become increasingly apparent that this method is associated with a low risk of leakage, which we should report. METHODS: The anastomotic technique described was used in all patients undergoing ileo-colic anastomosis or closure of ileostomy by surgeon 1 (1994-2015) and in all ileo-colic anastomoses by surgeon 2 (2007-2015). All patients had a widely patent anastomosis constructed by two firings of a linear cutting stapler, as previously described. Additionally, the entire staple line was carefully oversewn with interrupted, inverting 4/0 polydioxanone sutures. Anastomotic leak was defined as a patient requiring re-operation or radiological drainage. RESULTS: One thousand and twelve patients underwent ileo-colic anastomosis and 685 patients underwent closure of ileostomy by surgeon 1, and 165 patients underwent ileo-colic anastomosis by surgeon 2. None of the 1862 patients required re-operation or radiological drainage for a leak (event rate 0%, 95% confidence interval 0-0.2%). However, there were three possible contained leaks treated successfully conservatively. The time taken to perform the actual anastomosis was measured in the last 30 ileo-colic resections. The median time was 42 min. CONCLUSION: While this method may well be too slow to gain widespread adoption, we hope this report encourages increased research into finding techniques with similar low leak rates.

Surgical and oncology trials for rectal cancer: who will participate?

BACKGROUND: The assessment of patients' and clinicians' willingness to participate in clinical trials is advisable as part of a feasibility exercise prior to the commencement of randomized controlled trials (RCTs) to ensure adequate support in terms of likely accrual to achieve the required sample size in a timely fashion. Furthermore, understanding why patients are unwilling to enter RCTs is imperative before the current trend of low participation can be reversed. METHODS: Patients, colorectal surgeons, and medical and radiation oncologists, were presented with 5 different, detailed treatments for locally advanced rectal cancer. They were asked whether they would be willing to enter an RCT comparing each treatment choice. Patients who would not participate were asked to indicate their reason for refusal. RESULTS: Patients' willingness to participate in each trial was consistently low (19% to 32%). Similar low levels of participation were indicated by each clinical subspecialty (15% to 38%). Of the scenarios, patients and clinicians were most willing to enter a trial investigating surgery plus preoperative radiotherapy. A dislike of randomization, a desire to be involved in decision-making, and quality of life considerations were the most commonly stated reasons for refusal. CONCLUSIONS: This study highlights the difficulties in performing RCTs in surgery and oncology. However, results suggest that improvements in communication regarding randomization and clinical trial processes and the actual, rather than perceived, side effects of treatments are strategies that may enhance patient participation.

Is it right to ignore learning-curve patients? Laparoscopic colorectal trials.

BACKGROUND: Increasingly complex, technically demanding surgical procedures utilizing emerging technologies have developed over recent decades and are recognized as having long 'learning curves'. This raises significant new issues. Ethically and scientifically, the outcome of a patient in the learning curve is as important as the outcome of a patient outside the learning curve. The aim of this study is to highlight just one aspect of our approach to learning-curve patients that should change. METHODS: The protocols of multicentre, prospective, randomized trials of patients undergoing either traditional open or laparoscopic surgery for colorectal cancer were reviewed. The number of patients excluded from the published trial results because they were in surgeons' learning curves was calculated. The seven editorials accompanying these publications were also examined for any mention of these patients. RESULTS: The eight studies identified had similar designs. All patients in the surgeons' laparoscopic learning curves, which were often several years long, were excluded from the actual trials. The total number of patients included in the trial publications was 5680. The number of patients excluded because they were in the surgeons' laparoscopic learning curves was >10 605. In none of the studies or accompanying editorials is there any mention of the total number of patients in the surgeons' learning curves, these patients' outcomes or how inclusion of their outcomes might have affected the overall results. CONCLUSION: Learning curves are inescapable in modern medicine. Our recognition of patients in these curves should evolve, with more data about them included in trial publications.

Adverse prognostic effect of methylation in colorectal cancer is reversed by microsatellite instability.

PURPOSE: DNA methylation is an important biologic event in colorectal cancer and in some cases is associated with the development of microsatellite instability (MSI). In this study, we sought to determine the prognostic significance of DNA methylation, both in univariate analysis and in concert with other clinicopathologic factors known to influence outcome. PATIENTS AND METHODS: Fresh tissue (625 cancers) was obtained from 605 individuals (age range, 29 to 99 years) undergoing curative surgery for colorectal cancer at one institution during a period of 8 years. Clinicopathologic details were recorded for all tumors, including stage, grade, type, vascular space invasion, and clinical follow-up to 5 years. Microsatellite status was assessed using standard markers. Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at methylated-in-tumor loci (MINT)1, MINT2, MINT12, and MINT31 loci were assessed by bisulfite-PCR. RESULTS: Patients with microsatellite unstable tumors (12%) had better disease-specific survival than those with microsatellite stable (MSS) tumors (univariate analysis: hazard ratio [HR], 0.53; 95% CI, 0.27 to 1.0). Overall survival of individuals with MSS tumors was influenced by three independently significant factors: tumor stage (HR, 7.3; 95% CI, 5.1 to 10.4), heavy tumor methylation (HR, 2.1; 95% CI, 1.1 to 4.0), and vascular space invasion (HR, 1.9; 95% CI, 1.3 to 2.9). In MSS tumors, methylation at any single site was not independently predictive of survival. Neither methylation nor microsatellite status predicted a favorable response to chemotherapy. CONCLUSION: DNA methylation is associated with a worse outcome in colorectal cancer, but this adverse prognostic influence is lost in those methylated tumors showing MSI. The mechanisms of these events warrant additional investigation.

Severe diverticulitis after heart, lung, and heart-lung transplantation.

BACKGROUND: In this study, we reviewed our experience with severe diverticulitis in patients who have undergone heart and/or lung transplantation to assess whether transplant recipients are at increased risk of having severe diverticulitis compared with the general population. METHODS: We reviewed the records of patients who underwent heart and/or lung transplantation from 1984 to 2000, inclusive, and identified patients with severe diverticulitis that required surgery or that resulted in death. We compared this incidence with the incidence of such complications in the general population, served by the same institution during a 2-year period, 1999 to 2000. RESULTS: A total of 953 patients underwent transplantation in the study period. The mean follow-up was 57 months, a total follow-up of 4528 patient-years. Nine patients (mean age, 54 years) had severe diverticulitis that required surgical intervention (8 patients) or that resulted in death (1 patient died without surgical intervention). During 1999 to 2000, 16 patients (mean age, 66 years) from the general population were treated for severe diverticulitis that required surgical intervention, 3 of whom died. From census and area health data, we found that the study institution serves approximately 90000 people older than 40 years, with a total follow-up of 180000 patient-years. The incidence rate ratio for severe diverticulitis when comparing the transplant with the non-transplant groups was 22.2 (95% confidence interval; 9.9-50.0; p < 0.001). CONCLUSIONS: Patients with severe diverticulitis who have undergone heart and/or lung transplantation can be treated surgically with a small mortality rate. Transplant recipients probably are at substantially increased risk of experiencing severe diverticulitis.

Current evidence does not support routine adjuvant radiotherapy for rectal cancer.

BACKGROUND: There is widespread support in the published literature for routine adjuvant radiotherapy for rectal cancer. METHODS: In the present paper, the current evidence regarding adjuvant radiotherapy is reviewed, particularly the most recent studies of preoperative radiotherapy (usually including patients with Stage I, II and III disease) and postoperative radiotherapy (usually for Stage II and III disease), and meta-analyses. Two questions in particular are addressed: Does radiotherapy improve survival when surgeons are able to achieve low local recurrence rates with surgery alone? Does radiotherapy improve patients' quality of life? RESULTS: Radiotherapy has only been demonstrated to significantly improve survival in one individual study and one recent meta-analysis. The local recurrence rates in the no-radiotherapy arm of these studies were 27% and 21-36.5%, respectively. In more recent studies, with lower local recurrence rates reflecting modern surgical standards, no survival advantage has been found. It is currently unknown whether radiotherapy improves patients' quality of life. Studies have demonstrated that radiotherapy has acute and long-term detrimental effects on quality of life. While local recurrence can be very debilitating, it can also be asymptomatic, and the overall effect of the local recurrence statistics found in adjuvant therapy studies on quality of life has not been systematically investigated. The most recent studies demonstrate that 17-20 patients need to undergo adjuvant radiotherapy to prevent one local recurrence. CONCLUSION: Current evidence does not support the widespread advocacy for routine adjuvant radiotherapy as used in the treatment arms of recent trials.

Multicenter randomized trial of centralized nurse-led telephone-based care coordination to improve outcomes after surgical resection for colorectal cancer: the CONNECT intervention.

PURPOSE: To investigate the effectiveness of a centralized, nurse-delivered telephone-based service to improve care coordination and patient-reported outcomes after surgery for colorectal cancer. PATIENTS AND METHODS: Patients with a newly diagnosed colorectal cancer were randomly assigned to the CONNECT intervention or usual care. Intervention-group patients received standardized calls from the centrally based nurse 3 and 10 days and 1, 3, and 6 months after discharge from hospital. Unmet supportive care needs, experience of care coordination, unplanned readmissions, emergency department presentations, distress, and quality of life (QOL) were assessed by questionnaire at 1, 3, and 6 months. RESULTS: Of 775 patients treated at 23 public and private hospitals in Australia, 387 were randomly assigned to the intervention group and 369 to the control group. There were no significant differences between groups in unmet supportive care needs, but these were consistently low in both groups at both follow-up time points. There were no differences between the groups in emergency department presentations (10.8% v 13.8%; P = .2) or unplanned hospital readmissions (8.6% v 10.5%; P = .4) at 1 month. By 6 months, 25.6% of intervention-group patients had reported an unplanned readmission compared with 27.9% of controls (P = .5). There were no significant differences in experience of care coordination, distress, or QOL between groups at any follow-up time point. CONCLUSION: This trial failed to demonstrate substantial benefit of a centralized system to provide standardized, telephone follow-up for postoperative patients with colorectal cancer. Future interventions could investigate a more tailored approach.

Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa.

Folate exists as functionally diverse species within cells. Although folate deficiency may contribute to DNA hypomethylation in colorectal cancer, findings on the association between total folate concentration and global DNA methylation have been inconsistent. This study determined global, LINE-1, and Alu DNA methylation in blood and colon of healthy and colorectal cancer patients and their relationship to folate distribution. Blood and normal mucosa from 112 colorectal cancer patients and 114 healthy people were analyzed for global DNA methylation and folate species distribution using liquid chromatography tandem mass spectrometry. Repeat element methylation was determined using end-specific PCR. Colorectal mucosa had lower global and repeat element DNA methylation compared with peripheral blood (P < 0.0001). After adjusting for age, sex and smoking history, global but not repeat element methylation was marginally higher in normal mucosa from colorectal cancer patients compared with healthy individuals. Colorectal mucosa from colorectal cancer subjects had lower 5-methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate levels than blood from the same individual. Blood folate levels should not be used as a surrogate for the levels in colorectal mucosa because there are marked differences in folate species distribution between the two tissues. Similarly, repeat element methylation is not a good surrogate measure of global DNA methylation in both blood and colonic mucosa. There was no evidence that mucosal global DNA methylation or folate distribution was related to the presence of cancer per se, suggesting that if abnormalities exist, they are confined to individual cells rather than the entire colon.