Aspects on diverticular disease

Objective: The aims of this thesis were to evaluate the influence of ethnicity and other sociodemographic factors on the rate of diverticular disease (DD) (Paper I), to compare findings specific for DD and acceptance of CT Colonography (CTC) and conventional Colonoscopy (CC) in patients examined after diverticulitis (AD) (Paper II), to evaluate the value of antibiotics in conservative treatment of patients with mild AD (Paper III) and to study patients with diverticular fistulas to the female genital tract (Paper IV). Methods: In paper I, Swedish national registers with information about health and socio-demographic indicators were used to study ethnicity and other socio-demographic factors and the risk of hospital admission due to DD in a national cohort (4.4 millions) followed prospectively over a period of ten years. Paper II was a prospective comparative study of 57 patients examined with CTC and CC respectively. Paper III was an observational study of 311 patients; all treated for AD and included mailed questionnaires. Paper IV reviewed evaluation, management, morbidity and outcome in 60 women treated for DD fistulas to the genital tract. Results: In all 25,123 patients were hospitalized because of DD during 1991-2000. The risk ratio (RR) of DD, after adjustment for age, sex and socio-economic indicators, was lower in non-western immigrants (RRs 0.5-0.7) compared with indigenous patients. The risk increased with time after settlement in Sweden. Women had a higher risk compared with men (R-R 1.50, CI 95% 1.46-1.54, p<0.001) and the difference increased with age. (Paper I) DD was found in 96 % of patients at CTC and in 90 % at colonoscopy. Eight suspected polyps sized ¡Ý5 mm were found in six patients. Patients experienced colonoscopy more discomforting (p<0.03), painful (p<0.001) and difficult (p<0.01) than CTC Seventyfour % of patients preferred CTC. (Paper II) During first hospitalisation, patients treated with antibiotics had a more pronounced inflammation compared with patients treated without antibiotics. If initially treated with antibiotics three patients (3 %) failed to respond to medical management and had surgery. Seven patients (4 %) treated without antibiotics failed to respond and antibiotics were then added. In all, 29 % of patients treated with antibiotics had further events (recurrent AD and/or subsequent surgery) during EU (mean 30 months, range 16-45), compared with 28 % (N.S.), if treated without antibiotics. In a multivariate analysis, antibiotics did not influence the risk for a further event (OR 1.03, Cl 95 % 0.61-1.74). (Paper III) The most common presenting symptoms in women with a DD fistula to the genital tract were vaginal discharge of faeces or gas (95 %) and 75 % of them had previously had a hysterectomy. 57/60 patients had surgery, sigmoid resection and anastomosis was performed in 51 and a Hartmann's procedure with colostomy in six patients. In all, 26 % of the patients experienced morbidity after surgery, including anastomotic dehiscence (n=4) and ureteric injury (n=3). All operated patients were cured from their fistulas and outcome was satisfactory in 86 %. (Paper IV) Conclusions: DD appears to be an acquired disorder and acculturation to a Western lifestyle has an impact on the risk for DD. Potential socio-demographic confounders, such as socio-economic status, residency and housing situation don't influence the risk. The diagnostic findings of CTC are comparable to colonoscopy in patients investigated after AD. CTC is less discomforting and preferred by a majority of patients. Thus, CTC seems to be a good alter-native in the follow-up of patients after AD. To omit antibiotics in the treatment of mild AD appears safe and does not influence the rate of further events. DD fistulas to the female genital tract mostly occur in elderly patients with a prior hysterectomy. Sigmoid resection and primary anastomosis is done safely in the majority of patients

High intake of dietary fibre from fruit and vegetables reduces the risk of hospitalisation for diverticular disease.

BACKGROUNDS AND AIMS: High intake of dietary fibres has been associated with a reduced risk of DD. However, reports on which type of dietary fibre intake that is most beneficial have been conflicting. The aim of this study was to investigate the association between different dietary fibres and hospitalisation due to diverticular disease (DD) of the colon. METHODS: This was a major cohort study. The Swedish Mammography Cohort and the Cohort of Swedish Men were linked to the Swedish Inpatient Register and the Causes of Death Register. Data on the intake of dietary fibre were collected through questionnaires. The effect of intake (in quartiles) of different types of dietary fibre on the incidence of hospitalisation due to DD was investigated using multivariable Cox regression. Estimates were adjusted according to age, BMI, physical activity, co-morbidity, intake of corticosteroids, smoking, alcohol intake and education level. RESULTS: Women with intake of fruit and vegetable fibres in the highest quartile (median 12.6 g/day) had a 30% decreased risk of hospitalisation compared to those with the lowest intake (4.1 g/day). Men within the highest quartile (10.3 g/day) had a 32% decreased risk compared to those with a low intake (2.9 g/day). High intake of fibres from cereals did not affect the risk. CONCLUSION: A high intake of fruits and vegetables may reduce the risk of hospitalisation due to DD. Intake of cereals did not influence the risk

Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III) : A multicentre, randomised, non-blinded, phase 3, non-inferiority trial

Background: Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. Methods: In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 × 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 × 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1·7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. Findings: Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33·4 months (range 18·2-62·2) in the short-course radiotherapy group and 19·3 months (8·5-39·5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33·3 months (range 17·8-114·3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1·44 [95% CI 0·41-5·11]; long-course radiotherapy with delay 2·24 [0·71-7·10]; p=0·48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (<1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0·59 [95% CI 0·36-0·97], long-course radiotherapy with delay 0·63 [0·38-1·04], p=0·075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0·61 [95% CI 0·45-0·83] p=0·001). Interpretation: Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery. Funding: Swedish Research Council, Swedish Cancer Society, Stockholm Cancer Society, and the Regional Agreement on Medical Training and Clinical Research in Stockholm

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10 -10), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10 -10) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10 -10) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.</p