Total mesorectal excision in MRI-defined low rectal cancer: multicentre study comparing oncological outcomes of robotic, laparoscopic and transanal total mesorectal excision in high-volume centres.

BACKGROUND: The routine use of MRI in rectal cancer treatment allows the use of a strict definition for low rectal cancer. This study aimed to compare minimally invasive total mesorectal excision in MRI-defined low rectal cancer in expert laparoscopic, transanal and robotic high-volume centres. METHODS: All MRI-defined low rectal cancer operated on between 2015 and 2017 in 11 Dutch centres were included. Primary outcomes were: R1 rate, total mesorectal excision quality and 3-year local recurrence and survivals (overall and disease free). Secondary outcomes included conversion rate, complications and whether there was a perioperative change in the preoperative treatment plan. RESULTS: Of 1071 eligible rectal cancers, 633 patients with low rectal cancer were identified. Quality of the total mesorectal excision specimen (P = 0.337), R1 rate (P = 0.107), conversion (P = 0.344), anastomotic leakage rate (P = 0.942), local recurrence (P = 0.809), overall survival (P = 0.436) and disease-free survival (P = 0.347) were comparable among the centres. The laparoscopic centre group had the highest rate of perioperative change in the preoperative treatment plan (10.4%), compared with robotic expert centres (5.2%) and transanal centres (2.1%), P = 0.004. The main reason for this change was stapling difficulty (43%), followed by low tumour location (29%). Multivariable analysis showed that laparoscopic surgery was the only independent risk factor for a change in the preoperative planned procedure, P = 0.024. CONCLUSION: Centres with expertise in all three minimally invasive total mesorectal excision techniques can achieve good oncological resection in the treatment of MRI-defined low rectal cancer. However, compared with robotic expert centres and transanal centres, patients treated in laparoscopic centres have an increased risk of a change in the preoperative intended procedure due to technical limitations.

Implications of the new MRI-based rectum definition according to the sigmoid take-off: multicentre cohort study.

BACKGROUND: The introduction of the sigmoid take-off definition might lead to a shift from rectal cancers to sigmoid cancers. The aim of this retrospective cohort study was to determine the clinical impact of the new definition. METHODS: In this multicentre retrospective cohort study, patients were included if they underwent an elective, curative total mesorectal excision for non-metastasized rectal cancer between January 2015 and December 2017, were registered in the Dutch Colorectal Audit as having a rectal cancer according to the previous definition, and if MRI was available. All selected rectal cancer cases were reassessed using the sigmoid take-off definition. The primary outcome was the number of patients reassessed with a sigmoid cancer. Secondary outcomes included differences between the newly defined rectal and sigmoid cancer patients in treatment, perioperative results, and 3-year oncological outcomes (overall and disease-free survivals, and local and systemic recurrences). RESULTS: Out of 1742 eligible patients, 1302 rectal cancer patients were included. Of these, 170 (13.1 per cent) were reclassified as having sigmoid cancer. Among these, 93 patients (54.7 per cent) would have been offered another adjuvant or neoadjuvant treatment according to the Dutch guideline. Patients with a sigmoid tumour after reassessment had a lower 30-day postoperative complication rate (33.5 versus 48.3 per cent, P < 0.001), lower reintervention rate (8.8 versus 17.4 per cent, P < 0.007), and a shorter length of stay (a median of 5 days (i.q.r. 4-7) versus a median of 6 days (i.q.r. 5-9), P < 0.001). Three-year oncological outcomes were comparable. CONCLUSION: Using the anatomical landmark of the sigmoid take-off, 13.1 per cent of the previously classified patients with rectal cancer had sigmoid cancer, and 54.7 per cent of these patients would have been treated differently with regard to neoadjuvant therapy or adjuvant therapy.

Comparison of three-year oncological results after restorative low anterior resection, non-restorative low anterior resection and abdominoperineal resection for rectal cancer.

INTRODUCTION: Oncological outcome might be influenced by the type of resection in total mesorectal excision (TME) for rectal cancer. The aim was to see if non-restorative LAR would have worse oncological outcome. A comparison was made between non-restorative low anterior resection (NRLAR), restorative low anterior resection (RLAR) and abdominoperineal resection (APR). MATERIALS AND METHODS: This retrospective cohort included data from patients undergoing TME for rectal cancer between 2015 and 2017 in eleven Dutch hospitals. A comparison was made for each different type of procedure (APR, NRLAR or RLAR). Primary outcome was 3-year overall survival (OS). Secondary outcomes included 3-year disease-free survival (DFS) and 3-year local recurrence (LR) rate. RESULTS: Of 998 patients 363 underwent APR, 132 NRLAR and 503 RLAR. Three-year OS was worse after NRLAR (78.2%) compared to APR (86.3%) and RLAR (92.2%, p < 0.001). This was confirmed in a multivariable Cox regression analysis (HR 1.85 (1.07, 3.19), p = 0.03). The 3-year DFS was also worse after NRLAR (60.3%), compared to APR (70.5%) and RLAR (80.1%, p < 0.001), HR 2.05 (1.42, 2.97), p < 0.001. The LR rate was 14.6% after NRLAR, 5.2% after APR and 4.8% after RLAR (p = 0.005), HR 3.22 (1.61, 6.47), p < 0.001. CONCLUSION: NRLAR might be associated with worse 3-year OS, DFS and LR rate compared to RLAR and APR.

Impact of a diverting ileostomy in total mesorectal excision with primary anastomosis for rectal cancer.

BACKGROUND: The role of diverting ileostomy in total mesorectal excision (TME) for rectal cancer with primary anastomosis is debated. The aim of this study is to gain insight in the clinical consequences of a diverting ileostomy, with respect to stoma rate at one year and stoma-related morbidity. METHODS: Patients undergoing TME with primary anastomosis for rectal cancer between 2015 and 2017 in eleven participating hospitals were included. Retrospectively, two groups were compared: patients with or without diverting ileostomy construction during primary surgery. Primary endpoint was stoma rate at one year. Secondary endpoints were severity and rate of anastomotic leakage, overall morbidity rate within thirty days and stoma (reversal) related morbidity. RESULTS: In 353 out of 595 patients (59.3%) a diverting ileostomy was constructed during primary surgery. Stoma rate at one year was 9.9% in the non-ileostomy group and 18.7% in the ileostomy group (p = 0.003). After correction for confounders, multivariate analysis showed that the construction of a diverting ileostomy during primary surgery was an independent risk factor for stoma at one year (OR 2.563 (95%CI 1.424-4.611), p = 0.002). Anastomotic leakage rate was 17.8% in the non-ileostomy group and 17.2% in the ileostomy group (p = 0.913). Overall 30-days morbidity rate was 37.6% in the non-ileostomy group and 56.1% in the ileostomy group (p < 0.001). Stoma reversal related morbidity rate was 17.9%. CONCLUSIONS: The stoma rate at one year was higher in patients with ileostomy construction during primary surgery. The incidence and severity of anastomotic leakage were not reduced by construction of an ileostomy. The morbidity related to the presence and reversal of a diverting ileostomy was substantial.

The learning curve of transanal total mesorectal excision for rectal cancer is associated with local recurrence: results from a multicentre external audit.

AIM: Transanal total mesorectal excision (TaTME) has been suggested as a potential solution for the resection of challenging mid and low rectal cancer. This relatively complex procedure has been implemented in many centres over the last years, despite the absence of long-term safety data. Recently, concern has arisen because of an increase in local recurrence in the implementation phase. The aim of this study was to assess the correlation between accumulated experience and local recurrences. METHOD: An independent clinical researcher performed an external audit of consecutive series of all TaTME procedures in six centres in the Netherlands. Kaplan-Meier estimated local recurrence rates were calculated and multivariate Cox proportional hazards regression analysis performed to assess risk factors for local recurrence. Primary outcome was the local recurrence rate in the initial implementation (cases 1-10), continued adoption (cases 11-40) and prolonged experience (case 41 onward). RESULTS: Six hundred and twenty-four consecutive patients underwent TaTME for rectal cancer with a median follow-up of 27 months (range 1-82 months). The estimated 2- and 3-year local recurrence rates were 4.6% and 6.6%, respectively. Cox proportional hazards regression revealed procedural experience to be an independent factor in multivariate analysis next to advanced stage (ycMRF+, pT3-4, pN+) and pelvic sepsis. Corrected analysis projected the 3-year local recurrence rates to be 9.7%, 3.3% and 3.5% for the implementation, continued adoption and prolonged experience cohorts, respectively. CONCLUSION: This multicentre study shows a high local recurrence rate (12.5%) after implementation of TaTME which lowers to an acceptable rate (3.4%) when experience increases. Therefore, intensified proctoring and further precautions must be implemented to reduce the unacceptably high risk of local recurrence at units starting this technique.

Implementation of robot-assisted total mesorectal excision by multiple surgeons in a large teaching hospital: Morbidity, long-term oncological and functional outcome.

BACKGROUND: Robot-assisted total mesorectal excision (TME) might offer benefits in less morbidity, better functional and long-term outcome over laparoscopic TME. METHODS: All consecutive patients undergoing robot-assisted TME for rectal cancer during implementation between May 2015 and December 2019 performed by five surgeons in a single centre were included. Outcomes included local recurrence rate at 3 years, conversion rate, circumferential resection margin (CRM) positivity rate, 30-day postoperative morbidity and outcomes of low anterior resection syndrome (LARS) questionnaires. RESULTS: In 105 robot-assisted TME, local recurrence rate at 3 years was 7.4%, conversion to open surgery rate was 8.6%, CRM positivity rate was 5.7%, 73.3% had good quality specimen, postoperative morbidity rate was 47.6% and anastomotic leakage rate was 9.0%. Incidence of major LARS was 55.3%. CONCLUSIONS: results of this study described acceptable morbidity, functional and long-term outcome during implementation of robotic TME for rectal cancer by multiple surgeons in a single centre.

Long-term oncological results after transanal total mesorectal excision for rectal carcinoma.

BACKGROUND: Transanal total mesorectal excision (TaTME) for mid and low rectal cancer has been shown to improve short-term outcomes, mostly due to lower conversion rates and with improved quality of the specimen. However, robust long-term oncological data supporting the encouraging clinical and pathological outcomes are lacking. METHODS: All consecutive patients undergoing TaTME with curative intent for mid or low rectal cancer in two referral centers in The Netherlands between January 2012 and April 2016 with a complete and minimum follow-up of 36 months were included. The primary outcome was local recurrence rate. Secondary outcomes were disease-free survival, overall survival and development of metastasis. RESULTS: There were 159 consecutive patients. Their mean age was 66.9 (10.2) years and 66.7% of all patients were men. Pathological analysis showed a complete mesorectum in 139 patients (87.4%), nearly complete in 16 (10.1%) and an incomplete mesorectum in 4 (2.5%). There was involvement of the CRM (< 1 mm) in one patient (0.6%) and no patients had involvement of the distal margin (< 5 mm). Final postoperative staging after neoadjuvant therapy was stage 0 in 11 patients (6.9%), stage I in 73 (45.9%), stage II in 31 (19.5%), stage III in 37 (23.3%) and stage IV in 7 (4.4%). The 3-year local recurrence rate was 2.0% and the 5-year local recurrence rate was 4.0%. Median time to local recurrence was 19.2 months. Distant metastases were found in 22 (13.8%) patients and were diagnosed after a median of 6.9 months (range 1.1-50.4) months. Disease-free survival was 92% at 3 years and 81% at 5 years. Overall survival was 83.6% at 3 years and 77.3% at 5 years. CONCLUSIONS: The long-term follow-up of the current cohort confirms the oncological safety and feasibility of TaTME in two high volume referral centers for rectal carcinoma. However, further robust and audited data must confirm current findings before widespread implementation of TaTME.

The Efficacy of an Ultrapure Alginate Gel in Reducing Adhesion Formation in a Rat Model of Blood Contamination.

BACKGROUND: Formation of peritoneal adhesions is the most frequent complication of abdominal and pelvic surgery and comprises a lifelong risk of adhesion-related morbidity and mortality. Some of the existing antiadhesive barriers are less effective in the presence of blood. In this study, we investigate the efficacy and safety of ultrapure alginate gel in the presence of blood. METHODS: In experiment 1 (30 rats), 1 mL ultrapure alginate gel was compared with no intervention in a model of cecal abrasion and persisting peritoneal bleeding by incision of the epigastric artery. In experiment 2 (30 rats), 2 mL ultrapure alginate gel was compared with no intervention in a model where a 1 mL blood clot was instilled intra-abdominally and a cecal resection was performed. The primary endpoint was the incidence and severity of adhesions after 14 d. RESULTS: In experiment 1, seven of 15 rats in the experimental group had intra-abdominal adhesions compared with 13 of 15 rats in the control group (P = 0.05); 3 of 15 rats had adhesions at the site of injury compared with 12 of 15 rats in the control group (P < 0.01). The severity and extent of adhesions was also reduced (P < 0.01). In experiment 2, 12 of 13 rats had adhesions compared with 13 of 14 rats in the control group (P = 1.00). CONCLUSIONS: Ultrapure alginate gel reduces the incidence and severity of adhesion in the presence of persisting bleeding, but not in a model of cecal resection and blood clot.

Quality of life, functional status and adhesiolysis during elective abdominal surgery.

BACKGROUND: Adhesiolysis during abdominal surgery can cause iatrogenic organ injury, increased operative time and a more complicated convalescence. We assessed the impact of adhesiolysis and adhesiolysis-related complications on quality of life and functional status following elective abdominal surgery. METHODS: Prospective cohort study, comparing patients requiring and not requiring adhesiolysis during an elective laparotomy or laparoscopy using the SF-36 and DASI questionnaire scores. RESULTS: 518 patients were included. Pre- and postoperative quality of life did not significantly differ between both groups. Patients with adhesiolysis had a significantly lower pre- and postoperative functional status (p < 0.01). Higher age, concomitant pulmonary disease, postoperative complications, readmissions and chronic abdominal pain 6 months after surgery were all associated with a significant and independent decline in quality of life and functional status six months after surgery. CONCLUSION: Adhesiolysis in itself does not affect functional status and quality of life six months after surgery. Postoperative complications, readmissions and chronic abdominal pain are associated with a lower health status.

Correlation Between Liver Volumetric Computed Tomography Results and Measured Liver Weight: A Tool for Preoperative Planning of Liver Transplant.

OBJECTIVES: Before liver transplant, it is necessary to know the size of the organ in advance of the procedure. We studied the correlation between liver volumetric computed tomography results and liver weight. MATERIALS AND METHODS: Postmortem volumetric computed tomography was conducted on cadavers before autopsy, and 3-dimensional liver volume was estimated with semiautomated software. Liver weight was then determined at autopsy. Linear regression and univariate analysis of variance results were used to determine the accuracy of volumetric 3-dimensional computed tomography in estimating liver weight. We also used 2-dimensional liver sizes to design a 2-dimensional formula to estimate liver volume. RESULTS: We found that 3-dimensional volumetric computed tomography was able to accurately estimate liver weight (standard error = 157 g) with a liver density of 0.99 g/mL. Intraobserver and interobserver variabilities were small. The 2-dimensional formula estimated liver weight slightly less accurately (standard error = 212 g). CONCLUSIONS: We conclude that liver weight can be estimated accurately with 3-dimensional volumetric computed tomography; estimates were more precise than with the 2-dimensional formula-based liver volume estimation. Volumetric computed tomography can be an important tool during preoperative workup before transplant surgery.

Effect of lanreotide on polycystic liver and kidneys in autosomal dominant polycystic kidney disease: an observational trial.

BACKGROUND & AIM: Several trials have demonstrated that somatostatin analogues decrease liver volume in mixed populations of patients with autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of lanreotide and possibly enhances risk for adverse events. The aim of this open-label clinical trial (RESOLVE trial) was to assess the efficacy of 6-month lanreotide treatment, 120 mg, subcutaneously every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. METHODS: Primary outcome was change in liver volume after 6 months; secondary outcomes were changes in kidney volume, estimated glomerular filtration rate (eGFR), symptom relief and health-related quality of life (Euro-Qol5D). We excluded patients with an eGFR <30 ml/min/1.73 m(2) . We used the Wilcoxon signed-rank test or paired two-sided t-test to analyze within-group differences. RESULTS: We included 43 ADPKD patients with polycystic liver disease (84% female, median age 50 years, mean eGFR 63 ml/min/1.73 m(2) ). Median liver volume decreased from 4859 ml to 4595 ml (-3.1%; P < 0.001), and median kidney volume decreased from 1023 ml to 1012 ml (-1.7%; P = 0.006). eGFR declined 3.5% after the first injection, remained stable up to study end, to decline again after lanreotide withdrawal. Lanreotide significantly relieved post-prandial fullness, shortness of breath and abdominal distension. Three participants had a suspected episode of hepatic or renal cyst infection during this study. CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely after starting lanreotide, stabilized thereafter and declined again after withdrawal. TRIAL REGISTRATION NUMBER: Clinical trials.gov NCT01354405 (REGISTRATION: 13 May 2011).

Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: results from a randomized controlled trial.

BACKGROUND & AIMS: Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by approximately 5% when given for 6-12 months. A pilot trial in 16 ADPKD patients demonstrated that sirolimus, an mTOR inhibitor, reduced PLD volume by 26%. The aim of this study was to assess the PLD volume reducing effect of everolimus and octreotide relative to octreotide monotherapy. METHODS: We designed a randomized controlled trial that compared 48 weeks of everolimus 2.5 mg daily, combined with octreotide 40 mg intramuscularly every 4 weeks, to octreotide monotherapy. We included PCLD and ADPKD patients. Exclusion criteria were MDRD-GFR <60 ml/min/1.73 m(2) and liver volume <2500 ml. Primary outcome was change in liver volume measured with CT-volumetry. RESULTS: We randomized 44 PLD patients (29 PCLD, 15 ADPKD, 89% female) to treatment with octreotide (n=23) or octreotide-everolimus (n=21). Liver volume decreased by 3.5% (p<0.01) in the monotherapy arm, compared to 3.8% with combination therapy (p<0.01). The difference between treatment arms was not significant (p=0.73). CONCLUSIONS: Adding everolimus to octreotide in PLD does not increase the liver volume reducing effect of octreotide.