Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Impact of time interval between multidisciplinary team meeting and intended pancreatoduodenectomy on oncological outcomes.

BACKGROUND: Dutch guidelines indicate that treatment of pancreatic head and periampullary malignancies should be started within 3 weeks of the multidisciplinary team (MDT) meeting. This study aimed to assess the impact of time to surgery on oncological outcomes. METHODS: This was a retrospective population-based cohort study of patients with pancreatic head and periampullary malignancies included in the Netherlands Cancer Registry. Patients scheduled for pancreatoduodenectomy and who were discussed in an MDT meeting from May 2012 to December 2016 were eligible. Time to surgery was defined as days between the final preoperative MDT meeting and surgery, categorized in tertiles (short interval, 18 days or less; intermediate, 19-32 days; long, 33 days or more). Oncological outcomes included overall survival, resection rate and R0 resection rate. RESULTS: A total of 2027 patients were included, of whom 677, 665 and 685 had a short, intermediate and long time interval to surgery respectively. Median time to surgery was 25 (i.q.r. 14-36) days. Longer time to surgery was not associated with overall survival (hazard ratio 0·99, 95 per cent c.i. 0·87 to 1·13; P = 0·929), resection rate (relative risk (RR) 0·96, 95 per cent c.i. 0·91 to 1·01; P = 0·091) or R0 resection rate (RR 1·01, 0·94 to 1·09; P = 0·733). Patients with pancreatic ductal adenocarcinoma and a long time interval had a lower resection rate (RR 0·92, 0·85 to 0·99; P = 0·029). DISCUSSION: A longer time interval between the last MDT meeting and pancreatoduodenectomy did not decrease overall survival.

ANTECEDENTES: Las guías holandesas señalan que el inicio del tratamiento de los cánceres de cabeza de páncreas o periampulares se realice durante las tres semanas posteriores a la reunión del equipo multidisciplinar. Este estudio tuvo como objetivo evaluar la repercusión del tiempo transcurrido hasta la cirugía en los resultados oncológicos. MÉTODOS: Se trataba de un estudio de cohortes retrospectivo de base poblacional de pacientes con tumores pancreáticos de cabeza y periampulares a partir del registro de cáncer holandés. Se incluyeron los pacientes programados para duodenopancreatectomía cefálica discutidos en una reunión de equipo multidisciplinario entre mayo de 2012 y diciembre de 2016. El tiempo hasta la cirugía se definió como los días transcurridos entre la reunión final del equipo multidisciplinar y la cirugía, clasificándose en terciles (corto ≤ 18 días; intermedio 19-32 días; largo ≥ 33 días). Los resultados oncológicos analizados fueron la supervivencia global, la tasa de resección y la tasa de resección R0. RESULTADOS: Se incluyeron 2.027 pacientes, de los que 677, 665 y 685 correspondieron a los terciles de intervalo corto, intermedio y largo, respectivamente. La mediana del tiempo hasta la cirugía fue de 25 días (rango intercuartílico 14-36). La existencia de un intervalo de tiempo largo hasta la cirugía no se asociaba con la supervivencia global (cociente de riesgos instantáneos, hazard ratio, HR 0,99; i.c. del 95% 0,87-1,13; P = 0,93), la tasa de resección (riesgo relativo, RR 0,96; i.c. del 95% 0,91-1,01; P = 0,09) o la tasa de resección R0 (RR 1,01; i.c. del 95% 0,94-1,09; P = 0,73). Los pacientes con adenocarcinoma ductal pancreático y mayor intervalo tuvieron una tasa de resección más baja (RR 0,92; i.c. del 95%: 0,85-0,99; P = 0,03). CONCLUSIÓN: Un mayor intervalo de tiempo entre la última reunión del equipo multidisciplinar y la duodenopancreatectomía cefálica no disminuyó la supervivencia global.

Multicentre study of non-surgical management of diverticulitis with abscess formation.

This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short-term treatment failure and emergency surgery respectively. Initial non-surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short- and long-term outcomes. Most do not need drainage.

Long-term follow-up of a multicentre cohort study on laparoscopic peritoneal lavage for perforated diverticulitis.

AIM: Laparoscopic peritoneal lavage has increasingly been investigated as a promising alternative to sigmoidectomy for perforated diverticulitis with purulent peritonitis. Most studies only reported outcomes up to 12 months. Therefore, the objective of this study was to evaluate long-term outcomes of patients treated with laparoscopic lavage. METHODS: Between 2008 and 2010, 38 patients treated with laparoscopic lavage for perforated diverticulitis in 10 Dutch teaching hospitals were included. Long-term follow-up data on patient outcomes, e.g. diverticulitis recurrence, reoperations and readmissions, were collected retrospectively. The characteristics of patients with recurrent diverticulitis or complications requiring surgery or leading to death, categorized as 'overall complicated outcome', were compared with patients who developed no complications or complications not requiring surgery. RESULTS: The median follow-up was 46 months (interquartile range 7-77), during which 17 episodes of recurrent diverticulitis (seven complicated) in 12 patients (32%) occurred. Twelve patients (32%) required additional surgery with a total of 29 procedures. Fifteen patients (39%) had a total of 50 readmissions. Of initially successfully treated patients (n = 31), 12 (31%) had recurrent diverticulitis or other complications. At 90 days, 32 (84%) patients were alive without undergoing a sigmoidectomy. However, seven (22%) of these patients eventually had a sigmoidectomy after 90 days. Diverticulitis-related events occurred up to 6 years after the index procedure. CONCLUSION: Long-term diverticulitis recurrence, re-intervention and readmission rates after laparoscopic lavage were high. A complicated outcome was also seen in patients who had initially been treated successfully with laparoscopic lavage with relevant events occurring up to 6 years after initial surgery.

Laparoscopic combined resection of liver metastases and colorectal cancer: a multicenter, case-matched study using propensity scores.

BACKGROUND: Combined laparoscopic resection of liver metastases and colorectal cancer (LLCR) may hold benefits for selected patients but could increase complication rates. Previous studies have compared LLCR with liver resection alone. Propensity score-matched studies comparing LLCR with laparoscopic colorectal cancer resection (LCR) alone have not been performed. METHODS: A multicenter, case-matched study was performed comparing LLCR (2009-2016, 4 centers) with LCR alone (2009-2016, 2 centers). Patients were matched based on propensity scores in a 1:1 ratio. Propensity scores were calculated with the following preoperative variables: age, sex, ASA grade, neoadjuvant radiotherapy, type of colorectal resection and T and N stage of the primary tumor. Outcomes were compared using paired tests. RESULTS: Out of 1020 LCR and 64 LLCR procedures, 122 (2 × 61) patients could be matched. All 61 laparoscopic liver resections were minor hepatectomies, mostly because of a solitary liver metastasis (n = 44, 69%) of small size (≤ 3 cm) (n = 50, 78%). LLCR was associated with a modest increase in operative time [206 (166-308) vs. 197 (148-231) min, p = 0.057] and blood loss [200 (100-700) vs. 75 (5-200) ml, p = 0.011]. The rate of Clavien-Dindo grade 3 or higher complications [9 (15%) vs. 13 (21%), p = 0.418], anastomotic leakage [5 (8%) vs. 4 (7%), p = 1.0], conversion rate [3 (5%) vs. 5 (8%), p = 0.687] and 30-day mortality [0 vs. 1 (2%), p = 1.0] did not differ between LLCR and LCR. CONCLUSION: In selected patients requiring minor hepatectomy, LLCR can be safely performed without increasing the risk of postoperative morbidity compared to LCR alone.

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

BACKGROUND: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. DISCUSSION: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. TRIAL REGISTRATION: ClincalTrials.gov: NCT02243735 .

Small bowel obstruction, incisional hernia and survival after laparoscopic and open colonic resection (LAFA study).

BACKGROUND: Short-term advantages to laparoscopic surgery are well described. This study compared medium- to long-term outcomes of a randomized clinical trial comparing laparoscopic and open colonic resection for cancer. METHODS: The case notes of patients included in the LAFA study (perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care) were reviewed 2-5 years after randomization for incisional hernia, adhesional small bowel obstruction (SBO), overall survival, cancer recurrence and quality of life (QoL). The laparoscopic and open groups were compared irrespective of fast-track or standard perioperative care. RESULTS: Data on incisional hernias, SBO, survival and recurrence were available for 399 of 400 patients: 208 laparoscopic and 191 open resections. These outcomes were corrected for duration of follow-up. Median follow-up was 3·4 (i.q.r. 2·6-4·4) years. Multivariable regression analysis showed that open resection was a risk factor for incisional hernia (odds ratio (OR) 2·44, 95 per cent confidence interval (c.i.) 1·12 to 5·26; P = 0·022) and SBO (OR 3·70, 1·07 to 12·50; P = 0·039). There were no differences in overall survival (hazard ratio 1·10, 95 per cent c.i. 0·67 to 1·80; P = 0·730) or in cumulative incidence of recurrence (P = 0·514) between the laparoscopic and open groups. There were no measured differences in QoL in 281 respondents (P > 0·350 for all scales). CONCLUSION: Laparoscopic colonic surgery led to fewer incisional hernia and adhesional SBO events. REGISTRATION NUMBER: NTR222 (http://www.trialregister.nl).

Lotus petal perforator flap for reconstruction of an extended chronic presacral defect after radiotherapy and rectal cancer resection.

AIM: As a result of their extent and complexity, pelvic wounds after surgery for anorectal malignancy often require a multidisciplinary approach to accomplish closure. This report describes a successful reconstruction using the lotus petal perforator flap. METHOD: This flap is based on perforators of the internal pudendal artery and was partially depithelialized for plugging the defect. RESULTS: Wound healing was achieved after 12 days. CONCLUSION: The lotus petal flap is a relatively simple and successful choice for reconstruction of an extended chronic presacral defect after radiotherapy and rectal cancer resection.

Systematic review of perioperative selective decontamination of the digestive tract in elective gastrointestinal surgery.

BACKGROUND: Studies on selective decontamination of the digestive tract (SDD) in elective gastrointestinal surgery have shown decreased rates of postoperative infection and anastomotic leakage. However, the prophylactic use of perioperative SDD in elective gastrointestinal surgery is not generally accepted. METHODS: A systematic review of randomized clinical trials (RCTs) was conducted to compare the effect of perioperative SDD with systemic antibiotics (SDD group) with systemic antibiotic prophylaxis alone (control group), using MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Endpoints included postoperative infection, anastomotic leakage, and in-hospital or 30-day mortality. RESULTS: Eight RCTs published between 1988 and 2011, with a total of 1668 patients (828 in the SDD group and 840 in the control group), were included in the meta-analysis. The total number of patients with infection (reported in 5 trials) was 77 (19.2 per cent) of 401 in the SDD group, compared with 118 (28.2 per cent) of 418 in the control group (odds ratio 0.58, 95 per cent confidence interval 0.42 to 0.82; P = 0.002). The incidence of anastomotic leakage was significantly lower in the SDD group: 19 (3.3 per cent) of 582 patients versus 44 (7.4 per cent) of 595 patients in the control group (odds ratio 0.42, 0.24 to 0.73; P = 0.002). CONCLUSION: This systematic review and meta-analysis suggests that a combination of perioperative SDD and perioperative intravenous antibiotics in elective gastrointestinal surgery reduces the rate of postoperative infection including anastomotic leakage compared with use of intravenous antibiotics alone.

Influence of age on clinical outcome of acute diverticulitis.

BACKGROUND: The controversy about the treatment of acute colonic diverticulitis in young patients continues. The discussion is focused on whether younger age is a risk factor for recurrence or a complicated course, thereby subject to different treatment choices. AIM: In this study, we investigated whether an episode of acute diverticulitis at a younger age (≤50 years) has a higher recurrence rate or a more severe outcome. MATERIAL AND METHODS: A retrospective cohort study was conducted in four teaching hospitals using hospital registry codes for diverticulitis. All patients diagnosed with acute diverticulitis between January 2004 and January 2012, confirmed by imaging, were included. RESULTS: A total of 1,441 consecutive patients were identified as having primary acute diverticulitis of the sigmoid colon. Four hundred and sixty-three patients (32.1%) were ≤50 years (group 1) and 978 patients (67.9%) were older than 50 years (group 2). Twenty patients (4.3%) needed emergency surgery, due to perforated diverticulitis, within 72 h at first presentation in group 1 compared to 77 patients (7.8%) in group 2 (p = 0.029). Surgery within 30 days was needed for 29 of 463 patient (6.2%) in group 1 and 104 of 978 patients (10.6%) in group 2 (p = 0.02). Recurrence rate after a median follow-up of 22 months was comparable among groups (25.6% (111 patients) in group 1 versus 23.8% (208 patients) in group 2; p = 0.278). Also, cumulative recurrence was comparable among groups. CONCLUSION: Younger age is neither associated with a more severe presentation of diverticulitis nor with a higher incidence in recurrence.

Cost-effectiveness of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery.

OBJECTIVE: We compared the routine use of perioperative selective decontamination of the digestive tract (SDD) for elective gastrointestinal surgery with placebo in a randomized controlled trial. Alongside this trial, a cost-effectiveness analysis from a provider perspective was performed. METHODS AND RESULTS: A total of 289 patients undergoing elective surgery of the digestive tract were randomized to either SDD (143 patients) or placebo (146 patients). Routine use of SDD led to less patients with an infectious complication compared with placebo (p = 0.028). Mean total costs per patient were slightly less (EUR 2,604; 95% CI -6,292 to 1,084) in patients randomized to SDD (EUR 12,031) compared to patients randomized to placebo (EUR 14,635). Costs of hospitalization were the main determinant of the cost difference between the groups. The incremental cost-effectiveness ratio per prevented occurrence of ≥1 infectious complications per patient was -EUR 23,164, indicating the superiority of SDD over placebo. CONCLUSION: This study shows that in patients undergoing elective gastrointestinal surgery, the routine use of SDD is less expensive and economically more efficient than placebo in reducing the number of patients with infectious complications.

Predictors of recurrence of prolapse after procedure for prolapse and haemorrhoids.

AIM: The procedure for prolapse and haemorrhoids (PPH) is an effective surgical therapy for symptomatic haemorrhoids. Compared with haemorrhoidectomy, meta-analysis has shown PPH to be less painful, with higher patient satisfaction and a quicker return to work, but at the cost of higher prolapse recurrence rates. This is the first report describing predictors of prolapse recurrence after PPH. METHOD: A cohort of patients with symptomatic haemorrhoids, treated with PPH in our hospital between 2002 and 2009, was retrospectively analysed. Multivariate analysis was performed to identify patient-related and perioperative predictors associated with persisting prolapse and prolapse recurrence. RESULTS: In total, 159 consecutively enrolled patients were analysed. Persistence and recurrence of prolapse was observed in 16% of the patients. Increased surgical experience showed a trend towards lower recurrence rates. Multivariate analysis identified female gender, long duration of PPH surgery and the absence of muscle tissue in the resected specimen as independent predictors of postoperative persistence of prolapse of haemorrhoids. The absence of prior treatment with rubber band ligation (RBL) as well as increased PPH experience at the hospital showed a trend towards a higher rate of prolapse recurrence. CONCLUSION: In order to reduce recurrence of prolapse, PPH should be performed by a surgeon with adequate PPH experience, patients should be treated with RBL prior to PPH and a resection of mucosa with underlying muscle fibres should be strived for.

J-pouch vs side-to-end coloanal anastomosis after preoperative radiotherapy and total mesorectal excision for rectal cancer: a multicentre randomized trial.

AIM: Comparison of functional and surgical outcome of the J-pouch with the side-to-end coloanal anastomosis after preoperative radiotherapy and total mesorectal excision in rectal cancer patients. METHOD: In a multicentre study, patients with a carcinoma of the lower two-thirds of the rectum were randomized to either a J-pouch or a side-to-end reconstruction. Primary outcome was function of the neorectum 1 year after surgery. A functional outcome [COloREctal Functional Outcome (COREFO)] questionnaire, and two quality of life questionnaires (EORTC-QLQ-CR38 and SF-36) were to be completed by all participants preoperatively, and 4 and 12 months postoperatively. Independent data managers recorded surgical outcome. A group size of 30 patients in each group was calculated based on a 15-point difference of the COREFO scale. RESULTS: In total, 107 patients were randomized, 55 in the J-pouch group and 52 in the side-to-end anastomosis group. The COREFO incontinence scale at 4 months and the total functional outcome at 4 and 12 months showed better results for the J-pouch group in comparison with the side-to-end anastomosis group. The remaining COREFO scales (frequency, social impact, stool-related aspects and bowel medication), surgical outcome (complications, reoperations, length of hospital stay, readmissions and mortality) and quality of life did not show significant differences between treatment groups. CONCLUSION: The overall results of a coloanal J-pouch and a side-to-end anastomosis are comparable, although functional results are slightly better with a J-pouch. The side-to-end anastomosis is technically less demanding and therefore a justified alternative in sphincter-saving surgery.

Current application of selective decontamination of the digestive tract, perioperative antibiotics and mechanical bowel preparation in surgical departments in the Netherlands.

OBJECTIVE: To study the current application of selective decontamination of the digestive tract (SDD), the use of preoperative antibiotics and mechanical bowel preparation (MBP) in elective gastrointestinal (GI) surgery in surgical departments in the Netherlands. METHODS: A point prevalence survey was carried out and an online questionnaire was sent to GI surgeons of 86 different hospitals. RESULTS: The response rate was 74%. Only 4/64 (6.3%) of the Dutch surgical wards are currently using perioperative SDD as a prophylactic strategy to prevent postoperative infectious complications. The 4 hospitals using SDD on their surgical wards also use it on their ICUs. All hospitals make use of perioperative intravenous antibiotic prophylaxis in elective GI surgery. In most hospitals, a cephalosporin and metronidazole are applied (81.3 and 76.6%). MBP was used in 58 hospitals (90.6%) mainly in left colonic surgery. CONCLUSIONS: Perioperative SDD is rarely used in elective GI surgery in the Netherlands. Perioperative intravenous antibiotic prophylaxis is given in all Dutch hospitals, conforming to guidelines. Although the recent literature does not recommend MBP before surgery, it is still selectively used in 90.6% of the Dutch surgical departments, mainly in open or laparoscopic left colonic surgery (including sigmoid resections).

Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery.

BACKGROUND: This randomized clinical trial analysed the effect of perioperative selective decontamination of the digestive tract (SDD) in elective gastrointestinal surgery on postoperative infectious complications and leakage. METHODS: All patients undergoing elective gastrointestinal surgery during a 5-year period were evaluated for inclusion. Randomized patients received either SDD (polymyxin B sulphate, tobramycin and amphotericin) or placebo in addition to standard antibiotic prophylaxis. The primary endpoint was postoperative infectious complications and anastomotic leakage during the hospital stay or 30 days after surgery. RESULTS: A total of 289 patients were randomized to either SDD (143) or placebo (146). Most patients (190, 65·7 per cent) underwent colonic surgery. There were 28 patients (19·6 per cent) with infectious complications in the SDD group compared with 45 (30·8 per cent) in the placebo group (P = 0·028). The incidence of anastomotic leakage in the SDD group was 6·3 per cent versus 15·1 per cent in the placebo group (P = 0·016). Hospital stay and mortality did not differ between groups. CONCLUSION: Perioperative SDD in elective gastrointestinal surgery combined with standard intravenous antibiotics reduced the rate of postoperative infectious complications and anastomotic leakage compared with standard intravenous antibiotics alone. Perioperative SD.D should be considered for patients undergoing gastrointestinal surgery. REGISTRATION NUMBER: P02.1187L (Dutch Central Committee on Research Involving Human Subjects).

Toxicity and complications of preoperative chemoradiotherapy for locally advanced rectal cancer.

BACKGROUND: Capecitabine is an attractive radiosensitizer. In this study acute toxicity and surgical complications were evaluated in patients with locally advanced rectal cancer following total mesorectal excision (TME) after preoperative chemoradiotherapy (CRT) with capecitabine. METHODS: Between 2004 and 2008, consecutive patients with clinical tumour category (cT) 3-4 (with a threatened circumferential resection margin or cT3 within 5 cm of the anal verge) or clinical node category 2 rectal cancer were treated with preoperative CRT (25 × 2 Gy, capecitabine 825 mg/m(2) twice daily, days 1-33). TME followed 6 weeks later. Toxicity was scored according to the Common Terminology Criteria (version 3.0) and Radiation Therapy Oncology Group scoring systems. Treatment-related surgical complications were evaluated for up to 30 days after discharge from hospital using the modified Clavien-Dindo classification. RESULTS: Some 147 patients were analysed. The mean cumulative dose of capecitabine was 95 per cent and 98·0 per cent of patients received at least 45 Gy. One patient died from sepsis following haematological toxicity. Grade 3-5 toxicity developed in 32 patients (21·8 per cent), especially diarrhoea (10·2 per cent) and radiation dermatitis (11·6 per cent). There were no deaths within 30 days after surgery. Anastomotic leakage and perineal wound complications developed after 13 of 47 low anterior resections and 23 of 62 abdominoperineal resections. Surgical reintervention was required in 30 patients. Twenty-seven patients (19·6 per cent) of 138 patients who had a laparotomy were readmitted within 30 days after initial hospital discharge. CONCLUSION: Preoperative CRT with capecitabine is associated with acceptable acute toxicity, significant surgical morbidity but minimal postoperative mortality.