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.

Cumulative 5-year Results of a Randomized Controlled Trial Comparing Biological Mesh With Primary Perineal Wound Closure After Extralevator Abdominoperineal Resection (BIOPEX-study).

OBJECTIVE: To determine long-term outcomes of a randomized trial (BIOPEX) comparing biological mesh and primary perineal closure in rectal cancer patients after extralevator abdominoperineal resection and preoperative radiotherapy, with a primary focus on symptomatic perineal hernia. SUMMARY BACKGROUND DATA: BIOPEX is the only randomized trial in this field, which was negative on its primary endpoint (30-day wound healing). METHODS: This was a posthoc secondary analysis of patients randomized in the BIOPEX trial to either biological mesh closure (n = 50; 2 dropouts) or primary perineal closure (n = 54; 1 dropout). Patients were followed for 5 years. Actuarial 5-year probabilities were determined by the Kaplan-Meier statistic. RESULTS: Actuarial 5-year symptomatic perineal hernia rates were 7% (95% CI, 0-30) after biological mesh closure versus 30% (95% CI, 10-49) after primary closure (P = 0.006). One patient (2%) in the biomesh group underwent elective perineal hernia repair, compared to 7 patients (13%) in the primary closure group (P = 0.062). Reoperations for small bowel obstruction were necessary in 1/48 patients (2%) and 5/53 patients (9%), respectively (P = 0.208). No significant differences were found for chronic perineal wound problems, locoregional recurrence, overall survival, and main domains of quality of life and functional outcome. CONCLUSIONS: Symptomatic perineal hernia rate at 5-year follow-up after abdominoperineal resection for rectal cancer was significantly lower after biological mesh closure. Biological mesh closure did not improve quality of life or functional outcomes.

The Patient Navigator: Can a systematically developed online health information tool improve patient participation and outcomes related to the consultation in older patients newly diagnosed with colorectal cancer?

BACKGROUND: Older cancer patients may search for health information online to prepare for their consultations. However, seeking information online can have negative effects, for instance increased anxiety due to finding incorrect or unclear information. In addition, existing online cancer information is not necessarily adapted to the needs of older patients, even though cancer is a disease often found in older individuals. OBJECTIVE: The aim of this study was to systematically develop, implement and evaluate an online health information tool for older cancer patients, the Patient Navigator, providing information that complements the consultation with healthcare providers. METHOD: For the development and evaluation of the Patient Navigator, the four phases of the MRC framework were used. In the first and second phase the Patient Navigator was developed and pilot tested based on previous research and sub-studies. During the third phase the Patient Navigator was implemented in four Dutch hospitals. In the last phase, a pilot RCT was conducted to evaluate the Patient Navigator in terms of usage (observational tracking data), user experience (self-reported satisfaction, involvement, cognitive load, active control, perceived relevance of the tool), patient participation (observational data during consultation), and patient outcomes related to the consultation (questionnaire data regarding anxiety, satisfaction, and information recall). Recently diagnosed colorectal cancer patients (N = 45) were randomly assigned to the control condition (usual care) or the experimental condition (usual care + Patient Navigator). RESULTS: The Patient Navigator was well used and evaluated positively. Patients who received the Patient Navigator contributed less during the consultation by using less words than patients in the control condition and experienced less anxiety two days after the consultation than patients in the control condition. CONCLUSION: Since the Patient Navigator was evaluated positively and decreased anxiety after the consultation, this tool is potentially a valuable addition to the consultation for patients. Usage of the Patient Navigator resulted in patients using less words during consultations, without impairing patients' satisfaction, possibly because information needs might be fulfilled by usage of the Patient Navigator. This could create the possibility to personalize communication during consultations and respond to other patient needs.

Robot-Assisted Total Mesorectal Excision Versus Laparoscopic Total Mesorectal Excision: A Retrospective Propensity Score-Matched Cohort Analysis in Experienced Centers.

BACKGROUND: The superiority of robot-assisted over laparoscopic total mesorectal excision has not been proven. Most studies do not consider the learning curve while comparing the surgical technique. OBJECTIVE: This study aims to compare laparoscopic with robot-assisted total mesorectal excision performed by surgeons who completed the learning curve of the technique. DESIGN: This is a multicenter retrospective propensity score-matched analysis. SETTINGS: The study was performed in 2 large, dedicated robot-assisted hospitals and 5 large, dedicated laparoscopic hospitals. PATIENTS: Patients were included if they underwent a robot-assisted or laparoscopic total mesorectal excision for rectal cancer with curative intent at a dedicated center for the minimally invasive technique between January 1, 2015, and December 31, 2017. INTERVENTIONS: We compared robot-assisted with laparoscopic total mesorectal excision. MAIN OUTCOME MEASURES: The main outcome was conversion to laparotomy during surgery. Secondary outcomes were postoperative morbidity and positive circumferential resection margin. RESULTS: A total of 884 patients were included and, after matching, 315 patients per treatment group remained. Conversion was similar between laparoscopic and robot-assisted total mesorectal excision (4.4% vs 2.5% (p = 0.20)). Positive circumferential resection margin was equal (3.2% vs 4.4% (p = 0.41)). Overall morbidity was comparable as well, although a lower rate of wound infections was observed in the robot-assisted group (5.7% vs 1.9% (p = 0.01)). More primary anastomoses were constructed in the robot-assisted group (50.8% vs 68.3% (p < 0.001)). Finally, more open procedures were performed in dedicated laparoscopic centers, with an overrepresentation of cT4N+ tumors in this group. LIMITATIONS: This is a retrospective multicenter cohort; however, propensity score matching was applied to control for confounding by indication. CONCLUSIONS: Robot-assisted and laparoscopic total mesorectal excision are equally safe in terms of short-term outcomes. However, with the robot-assisted approach, more primary anastomoses were constructed, and a lower wound infection rate was observed. See Video Abstract at http://links.lww.com/DCR/B677.ESCISIÓN MESORRECTAL TOTAL ASISTIDA POR ROBOT VERSUS ESCISIÓN MESORRECTAL TOTAL LAPAROSCÓPICA: UNA PUNTUACIÓN DE PROPENSIÓN RETROSPECTIVA ANÁLISIS DE COHORTES EMPAREJADAS EN CENTROS EXPERIMENTADOS. ANTECEDENTES: No se ha demostrado la superioridad de la escisión mesorrectal total asistida por robot sobre la laparoscópica. La mayoría de los estudios no tienen en cuenta la curva de aprendizaje al comparar la técnica quirúrgica. OBJETIVO: Este estudio tiene como objetivo comparar la escisión mesorrectal total laparoscópica con la asistida por robot realizada por cirujanos que completaron la curva de aprendizaje de la técnica. DISEO: Este es un análisis multicéntrico retrospectivo emparejado por puntuación de propensión. AJUSTES: El estudio se realizó en dos grandes hospitales dedicados asistidos por robots y cinco grandes hospitales laparoscópicos dedicados. PACIENTES: Se incluyeron pacientes que se sometieron a escisión mesorrectal total asistida por robot o laparoscópica para cáncer de recto con intención curativa, en un centro dedicado a la técnica mínimamente invasiva entre el 1 de enero de 2015 y el 31 de diciembre de 2017. INTERVENCIONES: Comparamos la escisión mesorrectal total asistida por robot con la laparoscópica. PRINCIPALES MEDIDAS DE RESULTADO: El principal resultado fue la conversión a laparotomía durante la cirugía. Los resultados secundarios fueron la morbilidad posoperatoria y el margen circunferencial positivo. RESULTADOS: Se incluyó a un total de 884 pacientes y, después de emparejar, quedaron 315 pacientes por grupo de tratamiento. La conversión fue similar entre la escisión mesorrectal total laparoscópica y asistida por robot (4,4% frente a 2,5% [p = 0,20]). El margen de resección circunferencial positivo fue igual (3,2% vs 4,4% [p = 0,41]). La morbilidad general también fue comparable, aunque se observó una menor tasa de infecciones de heridas en el grupo asistido por robot (5,7% frente a 1,9% [p = 0,01]). Se construyeron más anastomosis primarias en el grupo asistido por robot (50,8% frente a 68,3% [p < 0,001]). Finalmente, se realizaron procedimientos más abiertos en centros laparoscópicos dedicados, con una sobrerrepresentación de tumores cT4N + en este grupo. LIMITACIONES: Ésta es una cohorte multicéntrica retrospectiva; sin embargo, se aplicó el emparejamiento por puntuación de propensión para controlar los factores de confusión por indicación. CONCLUSIONES: La escisión mesorrectal total asistida por robot y laparoscópica son igualmente seguras en términos de resultados a corto plazo. Sin embargo, con el abordaje asistido por robot, se construyeron más anastomosis primarias y se observó una menor tasa de infección de la herida. Consulte Video Resumen en http://links.lww.com/DCR/B677. (Traducción-Dr. Gonzalo Hagerman).

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial.

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018.

Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: study protocol of a randomised controlled multicentre trial (BIOPEX-2 study).

BACKGROUND: Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer. METHODS: Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function. DISCUSSION: The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place. TRIAL REGISTRATION: The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019.

Transanal Endoscopic Microsurgery with or without Completion Total Mesorectal Excision for T2 and T3 Rectal Carcinoma.

AIM: Transanal endoscopic microsurgery (TEM) is used for the resection of large rectal adenomas and well or moderately differentiated T1 carcinomas. Due to difficulty in preoperative staging, final pathology may reveal a carcinoma not suitable for TEM. Although completion total mesorectal excision is considered standard of care in T2 or more invasive carcinomas, this completion surgery is not always performed. The purpose of this article is to evaluate the outcome of patients after TEM-only, when completion surgery would be indicated. METHODS: In this retrospective multicenter, observational cohort study, outcome after TEM-only (n = 41) and completion surgery (n = 40) following TEM for a pT2-3 rectal adenocarcinoma was compared. RESULTS: Median follow-up was 29 months for the TEM-only group and 31 months for the completion surgery group. Local recurrence rate was 35 and 11% for the TEM-only and completion surgery groups respectively. Distant metastasis occurred in 16% of the patients in both groups. The 3-year overall survival was 63% in the TEM-only group and 91% in the completion surgery group respectively. Three-year disease-specific survival was 91 versus 93% respectively. CONCLUSIONS: Although local recurrence after TEM-only for pT2-3 rectal cancer is worse compared to the recurrence that occurs after completion surgery, disease-specific survival is comparable between both groups. The lower unadjusted overall survival in the TEM-only group indicates that TEM-only may be a valid alternative in older and frail patients, especially when high morbidity of completion surgery is taken into consideration. Nevertheless, completion surgery should always be advised when curation is intended.

Is there a difference in laparoscopic cholecystectomy performed in a teaching hospital or a general hospital in The Netherlands?

Introduction: Laparoscopic cholecystectomy may have a complicated course with severe complications such as bile duct injury. Studies in other countries than the Netherlands report ambivalent results regarding the influence of a residency program on patient safety, efficacy and financial consequences. This study aims to determine whether there is a difference between laparoscopic cholecystectomy performed in a teaching hospital or a non-teaching general hospital in Dutch clinics. Materials and methods: A prospective cohort study was performed to examine the safety of laparoscopic cholecystectomies in a teaching hospital with a residency program and a general hospital without surgical residents. All consecutive cholecystectomies in these two hospitals between September 2014 and March 2015 were included. Patient characteristics, operative procedure, level of experience, operation time, per- and postoperative complications, mortality, length of hospital stay, re-admittance and conversions to laparotomy were analyzed. Results: A total of 294 consecutive cholecystectomies were performed in both hospitals. Cholecystectomies performed in the teaching hospital took an average of 25 min longer to complete compared with a non-residency setting. Both the number of conversions and the number of re-admissions were not significantly different between both clinics. The residency program showed smaller peroperative liver lesions along with more postoperative complications, with most complications in patients that required a conversion. Discussion: Current practice where residents perform supervised cholecystectomies should not be discouraged. We believe that is safe and lead to an acceptable increase in operation time.

Organ Preservation in Rectal Cancer After Chemoradiation: Should We Extend the Observation Period in Patients with a Clinical Near-Complete Response?

BACKGROUND: To assess whether extending the observation period in patients with a near clinical complete response (near cCR) after chemoradiation (CRT) leads to an impaired oncological outcome. METHODS: Patients who had a clinical complete response (cCR) 8-10 weeks after CRT restaging with magnetic resonance imaging and endoscopy were offered a watch-and-wait strategy (W&W1), while patients with a near cCR were offered to undergo local excision or a second restaging 6-12 weeks later. Patients who achieved a cCR at the second restaging were also offered a watch-and-wait strategy (W&W2). RESULTS: Overall, 102 patients with a cCR at the first restaging immediately entered the W&W1, while the remaining 68 patients had a near cCR: 19 patients underwent transanal endoscopic microsurgery and 49 patients opted for a second restaging. Additionally, 44/49 (90%) patients showed a cCR at the second restaging and entered the W&W2. Patients in the W&W1 group had a 2-year local regrowth-free rate (LRFR) of 84% and 2-year overall survival (OS) of 99%, while patients in the W&W2 group had a 2-year LRFR of 73% and OS of 98% (p > 0.05). Multivariable Cox regression analyses showed that late inclusion was not a significant predictive factor for higher risk of LR or lower non-regrowth disease-free survival. CONCLUSIONS: Overall, 90% of patients with a near cCR 8-10 weeks after CRT will proceed to a cCR 6-12 weeks later; therefore, it seems logical to extend the observation period rather than to proceed to surgery. Although there is a non-significant increase in local regrowth rate in these patients, it does not seem to impact the oncological outcome.

Biological Mesh Closure of the Pelvic Floor After Extralevator Abdominoperineal Resection for Rectal Cancer: A Multicenter Randomized Controlled Trial (the BIOPEX-study).

OBJECTIVE: To determine the effect of biological mesh closure on perineal wound healing after extralevator abdominoperineal resection (eAPR). BACKGROUND: Perineal wound complications frequently occur after eAPR with preoperative radiotherapy for rectal cancer. Cohort studies have suggested that biological mesh closure of the pelvic floor improves perineal wound healing. METHODS: Patients were randomly assigned to primary closure (standard arm) or biological mesh closure (intervention arm). A non-cross-linked porcine acellular dermal mesh was sutured to the pelvic floor remnants in the intervention arm, followed by a layered closure of the ischioanal and subcutaneous fat and skin similar to the control intervention. The outcome of the randomization was concealed from the patient and perineal wound assessor. The primary endpoint was the rate of uncomplicated perineal wound healing defined as a Southampton wound score of less than 2 at 30 days postoperatively. Patients were followed for 1 year. RESULTS: In total, 104 patients were randomly assigned to primary closure (n = 54; 1 dropouts) and biological mesh closure (n = 50; 2 dropouts). Uncomplicated perineal wound healing rate at 30 days was 66% (33/50; 3 not evaluable) after primary closure, which did not significantly differ from 63% (30/48) after biological mesh closure [relative risk 1.056; 95% confidence interval (CI) 0.7854-1.4197; P = 0.7177). Freedom from perineal hernia at 1 year was 73% (95% CI 60.93-85.07) versus 87% (95% CI 77.49-96.51), respectively (P = 0.0316). CONCLUSIONS: Perineal wound healing after eAPR with preoperative radiotherapy for rectal cancer was not improved when using a biological mesh. A significantly lower 1-year perineal hernia rate after biological mesh closure is a promising secondary finding that needs longer follow-up to determine its clinical relevance.

MRI surveillance for the detection of local recurrence in rectal cancer after transanal endoscopic microsurgery.

OBJECTIVES: To evaluate diagnostic performance of follow-up MRI for detection of local recurrence of rectal cancer after transanal endoscopic microsurgery (TEM). METHODS: Between January 2006 and February 2014, 81 patients who underwent TEM were included. Two expert readers (R1 and R2), independently evaluated T2-weighted (T2W) MRI and diffusion-weighted (DWI) MRI for the detection of local recurrence, retrospectively, and recorded confidence on a five-point scale. Diagnostic performance of follow-up MRI was assessed using ROC-curve analysis and kappa statistics for the reproducibility between readers. RESULTS: 293 MRIs were performed, 203 included DWI. 18 (22%) patients developed a local recurrence: luminal 11, nodal two and both five. Areas under the curve (AUCs) for local recurrence detection were 0.72 (R1) and 0.80 (R2) for T2W-MRI. For DWI, AUCs were 0.70 (R1) and 0.89 (R2). For nodal recurrence AUCs were 0.72 (R1) and 0.80 (R2) for T2W-MRI. Reproducibility was good for T2W-MRI (κ0.68 for luminal and κ0.71 for nodal recurrence) and moderate for DWI (κ0.57). AUCs and reproducibility for recurrence detection increased during follow-up. CONCLUSIONS: Follow-up with MRI after TEM for rectal cancer is feasible. Postoperative changes can be confusing at the first postoperative MRI, but during follow-up diagnostic performance and reproducibility increase. KEY POINTS: • Follow-up with MRI is feasible for follow-up after TEM for rectal cancer. • DWI-MRI is a useful addition to detect recurrences after TEM. • Postoperative changes can be confusing and can lead to underestimation of recurrence. • Appearance of intermediate signal at T2W-MRI is suspicious for recurrence. • Nodal staging remains challenging.

Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer with Digital Rectal Examination, Endoscopy, and MRI: Selection for Organ-Saving Treatment.

BACKGROUND: The response to chemoradiotherapy (CRT) for rectal cancer can be assessed by clinical examination, consisting of digital rectal examination (DRE) and endoscopy, and by MRI. A high accuracy is required to select complete response (CR) for organ-preserving treatment. The aim of this study was to evaluate the value of clinical examination (endoscopy with or without biopsy and DRE), T2W-MRI, and diffusion-weighted MRI (DWI) for the detection of CR after CRT. METHODS: This prospective cohort study in a university hospital recruited 50 patients who underwent clinical assessment (DRE, endoscopy with or without biopsy), T2W-MRI, and DWI at 6-8 weeks after CRT. Confidence levels were used to score the likelihood of CR. The reference standard was histopathology or recurrence-free interval of >12 months in cases of wait-and-see approaches. Diagnostic performance was calculated by area under the receiver operator characteristics curve, with corresponding sensitivities and specificities. Strategies were assessed and compared by use of likelihood ratios. RESULTS: Seventeen (34 %) of 50 patients had a CR. Areas under the curve were 0.88 (0.78-1.00) for clinical assessment and 0.79 (0.66-0.92) for T2W-MRI and DWI. Combining the modalities led to a posttest probability for predicting a CR of 98 %. Conversely, when all modalities indicated residual tumor, 15 % of patients still experienced CR. CONCLUSIONS: Clinical assessment after CRT is the single most accurate modality for identification of CR after CRT. Addition of MRI with DWI further improves the diagnostic performance, and the combination can be recommended as the optimal strategy for a safe and accurate selection of CR after CRT.

Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study).

BACKGROUND: Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. DISCUSSION: The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia. TRAIL REGISTRATION NUMBER: NCT01927497 (Clinicaltrial.gov).

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes.

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates. Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Thirty-seven patients treated with the C-seal: protection of stapled colorectal anastomoses with a biodegradable sheath.

PURPOSE: The present study was performed to get a better insight in the incidence of anastomotic leakage leading to reintervention when using the C-seal: a biodegradable sheath that protects the stapled colorectal anastomosis from leakage. METHODS: The C-seal is a thin walled tube-like sheath that forms a protective sheath within the bowel lumen. Thirty-seven patients undergoing surgery with creation of a stapled colorectal anastomosis with C-seal were analyzed. Follow-up was completed until 3 months after surgery. RESULTS: One patient (3%) developed anastomotic leakage leading to reintervention. None of the 37 anastomoses was dismantled. One patient was diagnosed with a rectovaginal fistula. In three patients (8%), a perianastomotic abscess spontaneously drained. CONCLUSION: The incidence of anastomotic leakage leading to reintervention when using the C-seal (3%) is lower than expected based on the literature (11%). We have currently set-up a multicenter randomized trial to confirm the efficiency of the C-seal (www.csealtrial.nl).

Completion Total Mesorectal Excision: A Case-Matched Comparison With Primary Resection.

Objectives: The aim of this study was to compare the perioperative and oncological results of completion total mesorectal excision (cTME) versus primary total mesorectal excision (pTME). Background: Early-stage rectal cancer can be treated by local excision alone, which is associated with less surgical morbidity and improved functional outcomes compared with radical surgery. When high-risk histological features are present, cTME is indicated, with possible worse clinical and oncological outcomes compared to pTME. Methods: This retrospective cohort study included all patients that underwent TME surgery for rectal cancer performed in 11 centers in the Netherlands between 2015 and 2017. After case-matching, we compared cTME with pTME. The primary outcome was major postoperative morbidity. Secondary outcomes included the rate of restorative procedures and 3-year oncological outcomes. Results: In total 1069 patients were included, of which 35 underwent cTME. After matching (1:2 ratio), 29 cTME and 58 pTME were analyzed. No differences were found for major morbidity (27.6% vs 19.0%; P = 0.28) and abdominoperineal excision rate (31.0% vs 32.8%; P = 0.85) between cTME and pTME, respectively. Local recurrence (3.4% vs 8.6%; P = 0.43), systemic recurrence (3.4% vs 12.1%; P = 0.25), overall survival (93.1% vs 94.8%; P = 0.71), and disease-free survival (89.7% vs 81.0%; P = 0.43) were comparable between cTME and pTME. Conclusions: cTME is not associated with higher major morbidity, whereas the abdominoperineal excision rate and 3-year oncological outcomes are similar compared to pTME. Local excision as a diagnostic tool followed by completion surgery for early rectal cancer does not compromise outcomes and should still be considered as the treatment of early-stage rectal cancer.

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.

The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery.

BACKGROUND: The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer. METHODS/DESIGN: Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol. DISCUSSION: The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051).

MRI after chemoradiotherapy of rectal cancer: a useful tool to select patients for local excision.

PURPOSE: If identification of good responders to neoadjuvant chemoradiotherapy in rectal cancer is possible, there might be opportunities for local excision in selected patients. The aim of this study was to determine whether postchemoradiation MRI in rectal cancer can accurately identify ypT0 to 2/ypN0, because both features are essential for identification of good responders. METHODS: Seventy-nine patients (4 hospitals) underwent postchemoradiation MRI, 62 received a lymph node-specific contrast agent (ultrasmall superparamagnetic iron oxide). An expert and general radiologist prospectively predicted whether the tumor penetrated the mesorectal fat and whether nodes were sterilized after chemoradiation. Histology was the reference standard. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: For prediction of whether a tumor penetrated the bowel wall, there was an negative predictive value of 0.90 and 0.76 for the expert and general radiologist, respectively. The negative predictive value for prediction of nodal status was 0.95 and 0.85 for expert and general radiologist, respectively. CONCLUSION: This prospective multicenter study demonstrates that MRI with a lymph node-specific contrast agent interpreted by an expert radiologist can select ypT0 to 2/ypN0 rectal cancer with low risk of undetected nodal metastases or invasion through the bowel wall. These patients could thus have been selected for local excision. However, future studies will have to prove equal outcome of such a modified surgical approach compared with current practice.

DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial.

BACKGROUND: Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. METHODS/DESIGN: The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used.The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years. DISCUSSION: Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation. TRIAL REGISTRATION: (Trial register number: NTR1478).