Fredrik Hjern

Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis

The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow‐up.

The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer Resection Results From an International Registry

BACKGROUND The ERAS (enhanced recovery after surgery) care has been shown in randomized clinical trials to improve outcome after colorectal surgery compared to traditional care. The impact of different levels of compliance and specific elements, particularly out with a trial setting, is poorly understood. OBJECTIVE This study evaluated the individual impact of specific patient factors and perioperative enhanced recovery protocol compliance on postoperative outcome after elective primary colorectal cancer resection. METHODS The international, multicenter ERAS registry data, collected between November 2008 and March 2013, was reviewed. Patient demographics, disease characteristics, and perioperative ERAS protocol compliance were assessed. Linear regression was undertaken for primary admission duration and logistic regression for the development of any postoperative complication. FINDINGS A total of 1509 colonic and 843 rectal resections were undertaken in 13 centers from 6 countries. Median length of stay for colorectal resections was 6 days, with readmissions in 216 (9.2%), complications in 948 (40%), and reoperation in 167 (7.1%) of 2352 patients. Laparoscopic surgery was associated with reduced complications [odds ratio (OR) = 0.68; P < 0.001] and length of stay (OR = 0.83, P < 0.001). Increasing ERAS compliance was correlated with fewer complications (OR = 0.69, P < 0.001) and shorter primary hospital admission (OR = 0.88, P < 0.001). Shorter hospital stay was associated with preoperative carbohydrate and fluid loading (OR = 0.89, P = 0.001), and totally intravenous anesthesia (OR = 0.86, P < 0.001); longer stay was associated with intraoperative epidural analgesia (OR = 1.07, P = 0.019). Reduced postoperative complications were associated with restrictive perioperative intravenous fluids (OR = 0.35, P < 0.001). CONCLUSIONS This analysis has demonstrated that in a large, international cohort of patients, increasing compliance with an ERAS program and the use of laparoscopic surgery independently improve outcome.

Conservative treatment of acute colonic diverticulitis: Are antibiotics always mandatory?

Objective. Most patients admitted for acute colonic diverticulitis (AD) are managed conservatively and receive antibiotics, although it is uncertain whether all patients with AD benefit from this treatment. The aim of this study was to evaluate the influence of antibiotic treatment on outcome in the conservative management of patients with mild AD. Material and methods. A retrospective audit of 311 patients (64% F, mean age 60 years) hospitalized for AD was carried out. All patients were initially treated conservatively with observation and restriction of oral intake. Patients receiving antibiotics (n=118) were compared with patients treated with observation and restriction of oral intake only (n=193). Mean follow-up time (FU) was 30 months. Results. Inflammation in patients treated with antibiotics was more pronounced (laboratory parameters (C-reactive protein, white blood cell count) were higher (p<0.01), fever was more common (p<0.01) and CT grading of inflammation was classified as severe in a higher proportion (p<0.01)) compared with patients treated without antibiotics. When initially treated with antibiotics, 3 patients (3%) failed to respond to treatment and had to undergo surgery. There were 7 (4%) failures in patients initially treated without antibiotics, and antibiotics were then added. During FU, 29% of patients treated with antibiotics had further events (recurrent AD and/or subsequent surgery) compared with 28% (NS) among those treated without antibiotics. In a multivariate analysis, the risk of a further event was not influenced by antibiotic treatment (OR 1.03, CI 95% 0.61–1.74). Conclusions. Our results indicate that antibiotics are not mandatory in mild AD. Treatment without antibiotics appears to be safe and seems not to change the rate of further events. These results warrant further randomized prospective studies.

Obesity, Physical Inactivity, and Colonic Diverticular Disease Requiring Hospitalization in Women: A Prospective Cohort Study

OBJECTIVES:Lifestyle factors other than dietary fiber intake and risk for colonic diverticular disease have only been examined in few studies. The objective of this study was to investigate the association between obesity and physical inactivity and diverticular disease in a population-based cohort of women.METHODS:This was a prospective population-based cohort study. In all, 36,592 women, born 1914–1948, in the Swedish Mammography Cohort were followed 1997–2009. Body mass index (BMI; kg/m2), physical activity, diet, smoking, and other lifestyle factors were collected at baseline through questionnaires. Cases of diverticular disease were identified from the Swedish Patient and Death Registers. Relative risks (RRs) of diverticular disease requiring hospitalization (or being the cause of death) according to BMI and physical activity were estimated using Cox proportional hazards models. The multivariable models were adjusted for age; intake of dietary fiber; diabetes; hypertension; use of acetylsalicylate acid, non-steroid anti-inflammatory drug, or steroid medication; alcohol consumption; smoking; and educational level.RESULTS:During 12 years, 626 cases of incident diverticular disease requiring hospitalization were found. Two women were registered in the National Death Register only. In multivariable analysis, women with BMI 25–29.99 had 29% increased risk (RR=1.29; 95% confidence interval (CI): 1.08, 1.54) and obese women (BMI≥30) had 33% (1.33; 95% CI: 1.03–1.72) increased risk of diverticular disease compared to women with BMI 20–24.99. Exercise ≤30 min/day increased the risk for disease with 42% (1.42; 95% CI: 1.18–1.69) compared with exercise >30 min/day in multivariable analysis. Ninety-eight subjects were hospitalized due to complications; perforation or abscess. Women with BMI≥30 had a twofold (RR=2.00; 95% CI: 1.08–3.73; P=0.028) increased risk for complicated disease.CONCLUSIONS:Overweight, obesity, and physical inactivity among women increase diverticular disease requiring hospitalization.

Diverticular disease and migration – the influence of acculturation to a Western lifestyle on diverticular disease

Diverticular disease of the colon is more common in the Western world, compared with non‐Western countries.

Outcome of younger patients with acute diverticulitis

There is controversy over whether patients presenting with a primary attack of acute diverticulitis at a younger age are more prone to complications and recurrence than older patients.

Smoking and the risk of diverticular disease in women

The relationship between smoking and the risk of diverticular disease is unclear. An observational cohort study was undertaken to investigate the association between smoking and diverticular disease.

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.

Functional and Anatomic Outcome After Transvaginal Rectocele Repair Using Collagen Mesh: A Prospective Study

PURPOSEThis study was designed to evaluate rectocele repair using collagen mesh.METHODS32 female patients underwent surgical repair using collagen mesh. Outcome was assessed in 29 patients and preoperative assessment included standardized questionnaire, clinical examination, and defecography. At the six-month follow-up, patients answered a standardized questionnaire and underwent clinical examination. At the 12-month follow-up, patients answered a standardized questionnaire, underwent clinical examination, and defecography.RESULTSPreoperatively, 26 patients had a Stage II and 3 patients had a Stage III rectocele. At the 6-month follow-up, five patients had rectocele ≥ Stage II (P < 0.001) and at the 12-month follow-up, seven patients had rectocele ≥ Stage II (P < 0.001) at clinical examination. At the preoperative defecography, all patients presented a rectocele. At the 12-month defecography, 14 patients had no rectocele (P < 0.001) and 15 had a rectocele. At the six-month follow-up, there was a significant decrease in rectal emptying difficulties, need of digital support of the posterior vaginal wall at defecation, and defecation frequency. At the 12-month follow-up, symptom improvement remained, but was less pronounced.CONCLUSIONSRectocele repair using collagen mesh improved anatomic support, but there is a substantial risk for recurrence with unsatisfactory anatomic and functional outcome one year after surgery. Rectocele repair using mesh was not associated with an increased risk of dyspareunia. Rectocele repair using biomaterial mesh reinforcement needs further evaluation before adopted into clinical practice.

Diverticular disease and the risk of colon cancer – a population-based case–control study

Aliment Pharmacol Ther 2011; 34: 675–681