Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial.

BACKGROUND: As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored. PATIENTS AND METHODS: Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS-HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm. RESULTS: Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively. CONCLUSIONS: In patients with resectable CPM randomized to perioperative systemic therapy or CRS-HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial's previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.

Deep endometriosis muscular infiltration of the bowel wall: correlation between MRI and histopathology.

AIM: To assess the correlation between magnetic resonance imaging (MRI) and histopathology for predicting muscular infiltration of endometriosis in the bowel wall in patients undergoing colorectal resection. MATERIALS AND METHODS: All consecutive patients who underwent colorectal surgery for deep endometriosis (DE) with a preoperative MRI in a single tertiary care referral hospital between 2001 and 2019 were included in a prospective cohort. MRI images were revised by a single blinded radiologist. The MRI results regarding the infiltration depth (serosal, muscular, submucosal, or mucosal) and lesion expansion of DE were compared to histopathology. RESULTS: A total of 84 patients were eligible for evaluation. A sensitivity of 89% and positive predictive value of 97% was shown for predicting muscular involvement of the bowel wall. CONCLUSION: This study showed that MRI is valuable in predicting the involvement of the muscular layer of the colorectal wall. Therefore, in patients with symptomatic pelvic bowel endometriosis MRI is a useful tool in guiding the extent of colorectal surgery.

Long-term oncological outcomes after local excision of T1 rectal cancer.

BACKGROUND: A growing proportion of patients with early rectal cancer is treated by local excision only. The aim of this study was to evaluate long-term oncological outcomes and the impact of local recurrence on overall survival for surgical local excision in pT1 rectal cancer. METHODS: Patients who only underwent local excision for pT1 rectal cancer between 1997 and 2014 in two Dutch tertiary referral hospitals were included in this retrospective cohort study. The primary outcome was the local recurrence rate. Secondary outcomes were distant recurrence, overall survival and the impact of local recurrence on overall survival. RESULTS: A total of 150 patients (mean age 68.5 ± 10.7 years, 57.3% males) were included in the study. Median length of follow-up was 58.9 months (range 6-176 months). Local recurrence occurred in 22.7% (n = 34) of the patients, with a median time to local recurrence of 11.1 months (range 2.3-82.6 months). The vast majority of local recurrences were located in the lumen. Five-year overall survival was 82.0%, and landmark analyses showed that local recurrence significantly impacted overall survival at 6 and 36 months of follow-up (6 months, p = 0.034, 36 months, p = 0.036). CONCLUSIONS: Local recurrence rates after local excision of early rectal cancer can be substantial and may impact overall survival. Therefore, clinical decision-making should be based on patient- and tumour characteristics and should incorporate patient preferences.

Required distal mesorectal resection margin in partial mesorectal excision: a systematic review on distal mesorectal spread.

BACKGROUND: The required distal margin in partial mesorectal excision (PME) is controversial. The aim of this systematic review was to determine incidence and distance of distal mesorectal spread (DMS). METHODS: A systematic search was performed using PubMed, Embase and Google Scholar databases. Articles eligible for inclusion were studies reporting on the presence of distal mesorectal spread in patients with rectal cancer who underwent radical resection. RESULTS: Out of 2493 articles, 22 studies with a total of 1921 patients were included, of whom 340 underwent long-course neoadjuvant chemoradiotherapy (CRT). DMS was reported in 207 of 1921 (10.8%) specimens (1.2% in CRT group and 12.8% in non-CRT group), with specified distance of DMS relative to the tumor in 84 (40.6%) of the cases. Mean and median DMS were 20.2 and 20.0 mm, respectively. Distal margins of 40 mm and 30 mm would result in 10% and 32% residual tumor, respectively, which translates into 1% and 4% overall residual cancer risk given 11% incidence of DMS. The maximum reported DMS was 50 mm in 1 of 84 cases. In subgroup analysis, for T3, the mean DMS was 18.8 mm (range 8-40 mm) and 27.2 mm (range 10-40 mm) for T4 rectal cancer. CONCLUSIONS: DMS occurred in 11% of cases, with a maximum of 50 mm in less than 1% of the DMS cases. For PME, substantial overtreatment is present if a distal margin of 5 cm is routinely utilized. Prospective studies evaluating more limited margins based on high-quality preoperative magnetic resonance imaging and pathological assessment are required.

Laparoscopic Versus Robot-Assisted Versus Transanal Low Anterior Resection: 3-Year Oncologic Results for a Population-Based Cohort in Experienced Centers.

BACKGROUND: Laparoscopic, robot-assisted, and transanal total mesorectal excision are the minimally invasive techniques used most for rectal cancer surgery. Because data regarding oncologic results are lacking, this study aimed to compare these three techniques while taking the learning curve into account. METHODS: This retrospective population-based study cohort included all patients between 2015 and 2017 who underwent a low anterior resection at 11 dedicated centers that had completed the learning curve of the specific technique. The primary outcome was overall survival (OS) during a 3-year follow-up period. The secondary outcomes were 3-year disease-free survival (DFS) and 3-year local recurrence rate. Statistical analysis was performed using Cox-regression. RESULTS: The 617 patients enrolled in the study included 252 who underwent a laparoscopic resection, 205 who underwent a robot-assisted resection, and 160 who underwent a transanal low anterior resection. The oncologic outcomes were equal between the three techniques. The 3-year OS rate was 90% for laparoscopic resection, 90.4% for robot-assisted resection, and 87.6% for transanal low anterior resection. The 3-year DFS rate was 77.8% for laparoscopic resection, 75.8% for robot-assisted resection, and 78.8% for transanal low anterior resection. The 3-year local recurrence rate was in 6.1% for laparoscopic resection, 6.4% for robot-assisted resection, and 5.7% for transanal procedures. Cox-regression did not show a significant difference between the techniques while taking confounders into account. CONCLUSION: The oncologic results during the 3-year follow-up were good and comparable between laparoscopic, robot-assisted, and transanal total mesorectal technique at experienced centers. These techniques can be performed safely in experienced hands.

The awareness of radiologists for the presence of lateral lymph nodes in patients with locally advanced rectal cancer: a single-centre, retrospective cohort study.

OBJECTIVES: Enlarged lateral lymph nodes (LLNs) are associated with increased (lateral) local recurrence rates. Size and anatomical location should therefore always be reported by radiologists and discussed during multidisciplinary meetings. The objective was to investigate how often LLNs are mentioned in MRI reports in a tertiary referral centre. METHODS: A single - centre, retrospective study of 202 patients treated for primary rectal cancer between 2012 and 2020, with at least a T2 tumour located within 12cm of the anorectal junction. The radiology reports were written by 30-40 consultant radiologists. MRI scans were independently re-assessed by an expert radiologist. The primary outcome was how often the presence or absence of LLNs was mentioned in the initial report. RESULTS: Primary MRI reports explicitly mentioned the presence or absence of LLNs in 89 (44%) cases. Of the 43 reports with present LLNs, only one (1%) reported on all features such as size, location or malignant features. Expert review revealed 17 LLNs which were ≥ 7 mm (short-axis); two of these were not mentioned in the original reports. In 14/43 (33%) cases, LLNs were discussed during the primary multidisciplinary meeting, while 17/43 (40%) restaging MRI reports failed to report on the previously visible LLN. Reporting LLNs increased significantly with higher N-stage (p = .010) and over time (p = .042). CONCLUSIONS: Though improving with time, there is still limited consistency in reporting LLNs. Only 44% of primary MRI reports mentioned LLNs and relevant features of those LLNs were seldomly reported. Given the importance of this information for subsequent treatment; increased awareness, proper training and the use of templates are needed. KEY POINTS: • Comprehensive reporting of lateral lymph nodes in primary MRI reports was limited to less than 50%. • Lateral lymph nodes are not always discussed during primary multidisciplinary meetings or mentioned in restaging reports. • Improvements in the awareness and knowledge of lateral lymph nodes are needed to ensure adequate multidisciplinary treatment decisions.

Long-term stoma-related reinterventions after anterior resection for rectal cancer with or without anastomosis: population data from the Dutch snapshot study.

BACKGROUND: The aim of this study was to analyze the stoma-related reinterventions, complications and readmissions after an anterior resection for rectal cancer, based on a cross-sectional nationwide cohort study with 3-year follow-up. METHODS: Rectal cancer patients who underwent a resection with either a functional anastomosis, a defunctioned anastomosis, or Hartmann's procedure (HP) with an end colostomy in 2011 in 71 Dutch hospitals were included. The primary outcome was number of stoma-related reinterventions. RESULTS: Of the 2095 patients with rectal cancer, 1400 patients received an anterior resection and were included in this study; 257 received an initially functional anastomosis, 741 a defunctioned anastomosis, and 402 patients a HP. Of the 1400 included patients, 62% were males, 38% were females and the mean age was 67 years (SD 11.1). Following a primary functional anastomosis, 48 (19%) patients received a secondary stoma. Stoma-related complications occurred in six (2%) patients, requiring reintervention in one (0.4%) case. In the defunctioned anastomosis group, stoma-related complications were present in 92 (12%) patients, and required reintervention in 23 (3%) patients, in 10 (1%) of these more than 1 year after initial resection. Stoma-related complications occurred in 92 (23%) patients after a HP, and required reintervention in 39 (10%) patients in 17 (4%) of cases more than 1 year after initial resection. The permanent stoma rate was 11% and 20%, in the functional anastomosis and the defuctioned anastomosis group, respectively. The end colostomy in the HP group was reversed in 4% of cases. CONCLUSIONS: Construction of a stoma after resection for rectal cancer with preservation of the sphincter is accompanied with long-term stoma-related morbidity. Stoma complications are more frequent after a HP. Even after 1 year, a significant number of reinterventions are required.

Comparison of laparoscopic versus robot-assisted versus transanal total mesorectal excision surgery for rectal cancer: a retrospective propensity score-matched cohort study of short-term outcomes.

BACKGROUND: Laparoscopic total mesorectal excision (TME) surgery for rectal cancer has important technical limitations. Robot-assisted and transanal TME (TaTME) may overcome these limitations, potentially leading to lower conversion rates and reduced morbidity. However, comparative data between the three approaches are lacking. The aim of this study was to compare short-term outcomes for laparoscopic TME, robot-assisted TME and TaTME in expert centres. METHODS: Patients undergoing rectal cancer surgery between 2015 and 2017 in expert centres for laparoscopic, robot-assisted or TaTME were included. Outcomes for TME surgery performed by the specialized technique in the expert centres were compared after propensity score matching. The primary outcome was conversion rate. Secondary outcomes were morbidity and pathological outcomes. RESULTS: A total of 1078 patients were included. In rectal cancer surgery in general, the overall rate of primary anastomosis was 39.4, 61.9 and 61.9 per cent in laparoscopic, robot-assisted and TaTME centres respectively (P < 0.001). For specialized techniques in expert centres excluding abdominoperineal resection (APR), the rate of primary anastomosis was 66.7 per cent in laparoscopic, 89.8 per cent in robot-assisted and 84.3 per cent in TaTME (P < 0.001). Conversion rates were 3.7 , 4.6 and 1.9 per cent in laparoscopic, robot-assisted and TaTME respectively (P = 0.134). The number of incomplete specimens, circumferential resection margin involvement rate and morbidity rates did not differ. CONCLUSION: In the minimally invasive treatment of rectal cancer more primary anastomoses are created in robotic and TaTME expert centres.

The results of this study showed similar and acceptable short-term results for laparoscopic, robot-assisted and transanal total mesorectal excision performed in expert centres. In centres with robot-assisted or transanal technique, more primary anastomoses were made.

Rectal cancer lateral lymph nodes: multicentre study of the impact of obturator and internal iliac nodes on oncological outcomes.

BACKGROUND: In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes. METHODS: Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response. RESULTS: More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease. CONCLUSION: Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.

Functional complaints and quality of life after transanal total mesorectal excision: a meta-analysis.

BACKGROUND: Total mesorectal excision (TME) gives excellent oncological results in rectal cancer treatment, but patients may experience functional problems. A novel approach to performing TME is by single-port transanal minimally invasive surgery. This systematic review evaluated the functional outcomes and quality of life after transanal and laparoscopic TME. METHODS: A comprehensive search in PubMed, the Cochrane Library, Embase and the trial registers was conducted in May 2019. PRISMA guidelines were used. Data for meta-analysis were pooled using a random-effects model. RESULTS: A total of 11 660 studies were identified, from which 14 studies and six conference abstracts involving 846 patients (599 transanal TME, 247 laparoscopic TME) were included. A substantial number of patients experienced functional problems consistent with low anterior resection syndrome (LARS). Meta-analysis found no significant difference in major LARS between the two approaches (risk ratio 1·13, 95 per cent c.i. 0·94 to 1·35; P = 0·18). However, major heterogeneity was present in the studies together with poor reporting of functional baseline assessment. CONCLUSION: No differences in function were observed between transanal and laparoscopic TME.

ANTECEDENTES: La escisión total del mesorrecto (total mesorectal excision, TME) proporciona excelentes resultados oncológicos en el tratamiento del cáncer de recto, pero los pacientes pueden presentar trastornos funcionales. Un abordaje novedoso para realizar la TME es mediante cirugía transanal mínimamente invasiva de puerto único. En esta revisión sistemática se evaluaron los resultados funcionales y la calidad de vida después de TME transanal (TaTME) y TME laparoscópica (LapTME). MÉTODOS: En mayo de 2019 se realizó una búsqueda exhaustiva en las bases de datos de Pubmed, Biblioteca Cochrane, EMBASE y en los registros de ensayos clínicos. Se utilizaron las guías PRISMA. Los datos para el metaanálisis se agruparon utilizando un modelo de efectos aleatorios. RESULTADOS: Se identificaron un total de 11.660 estudios, de los cuales se incluyeron 14 estudios y 6 resúmenes de congresos con 846 pacientes (599 TaTME/247 LapTME). Un número sustancial de pacientes presentó trastornos funcionales consistentes con el síndrome de resección anterior baja (low anterior resection syndrome, LARS). El metaanálisis no encontró diferencias significativas en los porcentajes de LARS grave entre los dos abordajes (razón de oportunidades, odds ratio, OR 1,13; i.c. del 95% 0,94-1,35; P = 0,18). Sin embargo, los estudios globalmente presentaron una gran heterogeneidad, así como una deficiente información sobre la evaluación funcional basal. CONCLUSIÓN: No se observaron diferencias en la función entre TaTME y LapTME.

Local recurrence after local excision of early rectal cancer: a meta-analysis of completion TME, adjuvant (chemo)radiation, or no additional treatment.

BACKGROUND: The risks of local recurrence and treatment-related morbidity need to be balanced after local excision of early rectal cancer. The aim of this meta-analysis was to determine oncological outcomes after local excision of pT1-2 rectal cancer followed by no additional treatment (NAT), completion total mesorectal excision (cTME) or adjuvant (chemo)radiotherapy (aCRT). METHODS: A systematic search was conducted in PubMed, Embase and the Cochrane Library. The primary outcome was local recurrence. Statistical analysis included calculation of the weighted average of proportions. RESULTS: Some 73 studies comprising 4674 patients were included in the analysis. Sixty-two evaluated NAT, 13 cTME and 28 aCRT. The local recurrence rate for NAT among low-risk pT1 tumours was 6·7 (95 per cent c.i. 4·8 to 9·3) per cent. There were no local recurrences of low-risk pT1 tumours after cTME or aCRT. The local recurrence rate for high-risk pT1 tumours was 13·6 (8·0 to 22·0) per cent for local excision only, 4·1 (1·7 to 9·4) per cent for cTME and 3·9 (2·0 to 7·5) per cent for aCRT. Local recurrence rates for pT2 tumours were 28·9 (22·3 to 36·4) per cent with NAT, 4 (1 to 13) per cent after cTME and 14·7 (11·2 to 19·0) per cent after aCRT. CONCLUSION: There is a substantial risk of local recurrence in patients who receive no additional treatment after local excision, especially those with high-risk pT1 and pT2 rectal cancer. The lowest recurrence risk is provided by cTME; aCRT has outcomes comparable to those of cTME for high-risk pT1 tumours, but shows a higher risk for pT2 tumours.

ANTECEDENTES: Tras una resección temprana de un cáncer de recto localizado, hay que considerar el equilibrio entre el riesgo de recidiva local y la morbilidad relacionada con el tratamiento. El objetivo de este metaanálisis era determinar los resultados oncológicos tras la resección de un cáncer de recto pT1-T2 seguida de ningún tratamiento adicional (no additional treatment, NAT), escisión total del mesorrecto (completion total mesorectal excision, cTME) o quimiorradioterapia adyuvante (adjuvant chemoradiotherapy, aCRT). METHODS: Se llevó a cabo una búsqueda sistemática en PubMed, Embase y biblioteca Cochrane. La variable principal de resultado era la recidiva local (local recurrence, LR). En el análisis estadístico se calcularon las medias ponderadas de proporciones. RESULTADOS: Se incluyeron en el análisis 76 estudios con un total de 4.793 pacientes. NAT fue evaluada en 72 estudios, cTME en 13 y aCRT en 28. La tasa de LR para NAT en tumores pT1 de bajo riesgo era de 6,7% (i.c. del 95% 4,8-9,3). No se observaron casos de LR en tumores pT1 de bajo riesgo tras cTME o aCRT. La tasa de LR para tumores pT1 de alto riesgo fue de 13,6% (i.c. del 95% 8,0-22,0) para la resección local como único tratamiento, 4,1% (i.c. del 95% 1,7-9,4) para cTME y 3,9% (i.c. del 95% 2,0-7,5) para aCRT. La tasa de LR para tumores pT2 fue de 28,9% (i.c. del 95% 22,3-36,4) para NAT, 4,3% (i.c. del 95% 1,4-12,5) para cTME y 14,7% (i.c. del 95% 11,2-19,0) para aCRT. CONCLUSIÓN: Tras la resección local de cáncer pT1 de alto riesgo y pT2, existe un riesgo sustancial de recidiva local en ausencia de tratamiento adicional. La escisión total del mesorrecto se asocia con el menor riesgo de recidiva. La quimiorradioterapia adyuvante ofrece resultados similares a la escisión total del mesorrecto en tumores pT1 de alto riesgo, pero presenta un mayor riesgo en tumores pT2.

MRI cT1-2 rectal cancer staging accuracy: a population-based study.

BACKGROUND: Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS). METHODS: Patients with cT1-2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value. RESULTS: Of 7382 registered patients with cT1-2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1-2 N1 respectively. CONCLUSION: This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1-2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.

ANTECEDENTES: Una adecuada estadificación mediante resonancia magnética nuclear (RMN) de los cánceres de recto en estadios precoces es esencial para la toma de decisiones en una era en la existen diferentes opciones de tratamiento preservadoras del recto. El objetivo de este estudio de base poblacional fue determinar la precisión de la estadificación mediante RMN del cáncer de recto precoz en la práctica diaria, ya sea combinada o no con la ecografía endorectal (endorectal ultrasound, ERUS). MÉTODOS: Los pacientes con cáncer de recto en estadio cT1-2 que se sometieron a resección local o resección total del mesorrecto (total mesorectal excision, TME) sin (quimio) radioterapia neoadyuvante fueron seleccionados a partir del registro auditado ColoRectal holandés, entre el 1 de enero de 2011 y el 31 de diciembre de 2018. La precisión de las imágenes se expresó como sensibilidad, especificidad y valores predictivos positivo y negativo (positive- and negative predicting value, PPV / NPV). RESULTADOS: De un total de 7.382 pacientes registrados con cáncer de recto en estadio cT1-2, se incluyeron 5.539 pacientes (5.288 solamente RMN, 251 RMN + ERUS; 1.059 cT1 y 4.480 cT2). Los pacientes pT1 fueron sobreestadificados cuando se utilizó únicamente la RMN en un 54,7% de los casos (792/1.448) y cuando se combinó RMN y ERUS en un 31,0% (36/116). La infraestadificación de pT2 ocurrió en un 8,2% (197/2.388) y en un 27,9% (31/111), respectivamente. La RMN utilizada como única prueba sobreestadificó los casos pN0 en el 17,3% (570/3.303) y el VPP del estadio cN0 fue del 76,3% (2.733/3.583). De los 834 pacientes con estadio pT1N0, potencialmente adecuado para la resección local, 253 pacientes (30,3%) se clasificaron correctamente como cT1N0, y 484 (58,8%) y 97 (11,6%) pacientes se sobreestadificaron como cT2N0 y cT1-2N1, respectivamente. CONCLUSIÓN: Este estudio de base poblacional holandés en pacientes que se sometieron a una resección local o a cirugía TME por cáncer de recto cT1-2 con estadificación preoperatoria mediante RMN, muestra una considerable sobreestadificación, lo que indica las debilidades y oportunidades en las estrategias de preservación del recto.

Locoregional recurrences after transanal total mesorectal excision of rectal cancer during implementation.

BACKGROUND: Transanal total mesorectal excision (TaTME) has been proposed as an approach in patients with mid and low rectal cancer. The TaTME procedure has been introduced in the Netherlands in a structured training pathway, including proctoring. This study evaluated the local recurrence rate during the implementation phase of TaTME. METHODS: Oncological outcomes of the first ten TaTME procedures in each of 12 participating centres were collected as part of an external audit of procedure implementation. Data collected from a cohort of patients treated over a prolonged period in four centres were also collected to analyse learning curve effects. The primary outcome was the presence of locoregional recurrence. RESULTS: The implementation cohort of 120 patients had a median follow up of 21·9 months. Short-term outcomes included a positive circumferential resection margin rate of 5·0 per cent and anastomotic leakage rate of 17 per cent. The overall local recurrence rate in the implementation cohort was 10·0 per cent (12 of 120), with a mean(s.d.) interval to recurrence of 15·2(7·0) months. Multifocal local recurrence was present in eight of 12 patients. In the prolonged cohort (266 patients), the overall recurrence rate was 5·6 per cent (4·0 per cent after excluding the first 10 procedures at each centre). CONCLUSION: TaTME was associated with a multifocal local recurrence rate that may be related to suboptimal execution rather than the technique itself. Prolonged proctoring, optimization of the technique to avoid spillage, and quality control is recommended.

ANTECEDENTES: La escisión total del mesorrecto por vía transanal (Transanal Total Mesorectal Excision, TaTME) se ha propuesto como abordaje quirúrgico en pacientes con cáncer de recto medio e inferior. La técnica TaTME se ha introducido en los Países Bajos mediante un proceso de formación estructurado que incluye la supervisión. Este estudio evaluó el porcentaje de recidiva local durante la fase de implementación de TaTME. MÉTODOS: Se recogieron los resultados oncológicos de los primeros 10 procedimientos realizados mediante TaTME en cada uno de los 12 centros participantes como parte de una auditoría externa de implementación del procedimiento. Se reunió una cohorte más amplia de pacientes procedentes de 4 centros para analizar los efectos de la curva de aprendizaje. El criterio de valoración principal fue la presencia de recidiva locorregional. RESULTADOS: La cohorte de implementación de 120 pacientes tuvo una mediana de seguimiento de 21,9 meses. Los resultados a corto plazo incluyeron una tasa del margen de resección circunferencial positivo del 5% y una tasa de fuga anastomótica del 17,4%. La tasa global de recidiva local en la cohorte de implementación fue del 10% (12/120) con un intervalo medio de recidiva de 15,2 (DE 7) meses. El patrón de recidiva local fue multifocal en 8 de 12 casos (67%). En la cohorte ampliada (n = 266), la tasa global de recidiva fue del 5,6% (4,0%, excluyendo a los primeros 10 pacientes). CONCLUSIÓN: TaTME se asoció con un porcentaje de recidiva local multifocal que puede relacionarse con una ejecución subóptima, más que con la técnica en sí. Se recomienda una supervisión prolongada, la optimización de la técnica para evitar la diseminación tumoral, así como un control de calidad.

Interconnectivity between molecular subtypes and tumor stage in colorectal cancer.

BACKGROUND: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. METHODS: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. RESULTS: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008). CONCLUSIONS: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.

Structured training pathway and proctoring; multicenter results of the implementation of transanal total mesorectal excision (TaTME) in the Netherlands.

BACKGROUND: Transanal total mesorectal excision (TaTME) is a new complex technique with potential to improve the quality of surgical mesorectal excision for patients with mid and low rectal cancer. The procedure is technically challenging and has shown to be associated with a relative long learning curve which might hamper widespread adoption. Therefore, a national structured training pathway for TaTME has been set up in the Netherlands to allow safe implementation. The aim of this study was to monitor safety and efficacy of the training program with 12 centers. METHODS: Short-term outcomes of the first ten TaTME procedures were evaluated in 12 participating centers in the Netherlands within the national structured training pathway. Consecutive patients operated during and after the proctoring program for rectal carcinoma with curative intent were included. Primary outcome was the incidence of intraoperative complications, secondary outcomes included postoperative complications and pathological outcomes. RESULTS: In October 2018, 12 hospitals completed the training program and from each center the first 10 patients were included for evaluation. Intraoperative complications occurred in 4.9% of the cases. The clinicopathological outcome reported 100% for complete or nearly complete specimen, 100% negative distal resection margin, and the circumferential resection margin was positive in 5.0% of patients. Overall postoperative complication rate was 45.0%, with 19.2% Clavien-Dindo ≥ III and an anastomotic leak rate of 17.3%. CONCLUSIONS: This study shows that the nationwide structured training program for TaTME delivers safe implementation of TaTME in terms of intraoperative and pathology outcomes within the first ten consecutive cases in each center. However, postoperative morbidity is substantial even within a structured training pathway and surgeons should be aware of the learning curve of this new technique.

Transperineal minimally invasive APE: preliminary outcomes in a multicenter cohort.

BACKGROUND: Abdominoperineal excision (APE) for rectal cancer is associated with a relatively high risk of positive margins and postoperative morbidity, particularly related to perineal wound healing problems. It is unknown whether the use of a minimally invasive approach for the perineal part of these procedures can improve postoperative outcomes without oncological compromise. The aim of this study was to evaluate the feasibility of minimally invasive transperineal abdominoperineal excision (TpAPE) METHODS: This multicenter retrospective cohort study included all patients having TpAPE for primary low rectal cancer. The primary endpoint was the intraoperative complication rate. Secondary endpoints included major morbidity (Clavien-Dindo ≥ 3), histopathology results, and perineal wound healing. RESULTS: A total of 32 TpAPE procedures were performed in five centers. A bilateral extralevator APE (ELAPE) was performed in 17 patients (53%), a unilateral ELAPE in 7 (22%), and an APE in 8 (25%). Intraoperative complications occurred in five cases (16%) and severe postoperative morbidity in three cases (9%). There were no perioperative deaths. A positive margin (R1) was observed in four patients (13%) and specimen perforation occurred in two (6%). The unilateral extralevator TpAPE group had worse specimen quality and a higher proportion of R1 resections than the bilateral ELAPE or standard APE groups. The rate of uncomplicated perineal wound healing was 53% (n = 17) and three patients (9%) required surgical reintervention. CONCLUSIONS: TpAPE seems to be feasible with acceptable perioperative morbidity and a relatively low rate of perineal wound dehiscence, while histopathological outcomes remain suboptimal. Additional evaluation of the viability of this technique is needed in the form of a prospective trial with standardization of the procedure, indication, audit of outcomes and performed by surgeons with vast experience in transanal total mesorectal excision.

Diagnostic accuracy of urinary intestinal fatty acid binding protein in detecting colorectal anastomotic leakage.

BACKGROUND: Anastomotic leakage (AL) remains a severe complication following colorectal surgery, having a negative impact on both short- and long-term outcomes. Since timely detection could enable early intervention, there is a need for the development of novel and accurate, preferably, non-invasive markers. The aim of this study was to investigate whether urinary intestinal fatty acid binding protein (I-FABP) could serve as such a marker. METHODS: This prospective multicenter cross-sectional phase two diagnostic study was conducted at four centers in the Netherlands between March 2015 and November 2016. Urine samples of 15 patients with confirmed colorectal AL and 19 patients without colorectal AL on postoperative day 3 were included. Urinary I-FABP levels were determined using enzyme-linked immunosorbent assays and adjusted for urinary creatinine to compensate for renal dysfunction. RESULTS: Urinary I-FABP levels were significantly elevated in patients with confirmed AL compared to patients without AL on postoperative day 3 (median: 2.570 ng/ml vs 0.809 ng/ml, p = 0.006). The area under the receiver operating characteristics curve (AUROC) was 0.775, yielding a sensitivity of 80% and specificity of 74% at the optimal cutoff point (> 1.589 ng/ml). This difference remained significant after calculation of I-FABP/creatinine ratios (median: 0.564 ng/µmol vs. 0.158 ng/µmol, p = 0.040), with an AUROC of 0.709, sensitivity of 60% and specificity of 90% at the optimal cutoff point (> 0.469 ng/µmol). CONCLUSIONS: Levels of urinary I-FABP and urinary I-FABP/creatinine were significantly elevated in patients with confirmed AL following colorectal surgery, suggesting their potential as a non-invasive biomarker for colorectal anastomotic leakage.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

Urinary volatile organic compound markers and colorectal anastomotic leakage.

AIM: Inflammatory markers such as serum C-reactive protein (CRP) are used as routine markers to detect anastomotic leakage following colorectal surgery. However, CRP is characterized by a relatively low predictive value, emphasizing the need for the development of novel diagnostic approaches. Volatile organic compounds (VOCs) are gaseous metabolic products deriving from all conceivable bodily excrements and reflect (alterations in) the patient's physical status. Therefore, VOCs are increasingly considered as potential non-invasive diagnostic biomarkers. The aim of this study was to assess the diagnostic accuracy of urinary VOCs for colorectal anastomotic leakage. METHODS: In this explorative multicentre study, urinary VOC profiles of 22 patients with confirmed anastomotic leakage and 27 uneventful control patients following colorectal surgery were analysed by field asymmetric ion mobility spectrometry (FAIMS). RESULTS: Urinary VOCs of patients with anastomotic leakage could be distinguished from those of control patients with high accuracy: area under the receiver operating characteristics curve 0.91 (95% CI 0.81-1.00, P < 0.001), sensitivity 86% and specificity 93%. Serum CRP was significantly increased in patients with a confirmed anastomotic leak but with lower diagnostic accuracy compared to VOC analysis (area under the receiver operating characteristics curve 0.82, 95% CI 0.68-0.95, P < 0.001). Combining VOCs and CRP did not result in a significant improvement of the diagnostic performance compared to VOCs alone. CONCLUSION: Analysis by FAIMS allowed for discrimination between urinary VOC profiles of patients with a confirmed anastomotic leak and control patients following colorectal surgery. A superior accuracy compared to CRP and apparently high specificity was observed, underlining the potential as a non-invasive biomarker for the detection of colorectal anastomotic leakage.