Bromodomain Proteins Epigenetically Regulate the Mitotically Associated lncRNA MANCR in Triple Negative Breast Cancer Cells.

Long non-coding RNA (lncRNA)-mediated control of gene expression contributes to regulation of biological processes that include proliferation and phenotype, as well as compromised expression of genes that are functionally linked to cancer initiation and tumor progression. lncRNAs have emerged as novel targets and biomarkers in breast cancer. We have shown that mitotically associated lncRNA MANCR is expressed in triple-negative breast cancer (TNBC) cells and that it serves a critical role in promoting genome stability and survival in aggressive breast cancer cells. Using an siRNA strategy, we selectively depleted BRD2, BRD3, and BRD4, singly and in combination, to establish which bromodomain proteins regulate MANCR expression in TNBC cells. Our findings were confirmed by using in situ hybridization combined with immunofluorescence analysis that revealed BRD4, either alone or with BRD2 and BRD3, can support MANCR regulation of TNBC cells. Here we provide evidence for MANCR-responsive epigenetic control of super enhancers by histone modifications that are required for gene transcription to support cell survival and expression of the epithelial tumor phenotype in triple negative breast cancer cells.

Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis: Cost Analysis of a Randomized, Noninferiority Trial.

OBJECTIVE: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial.Background:Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. METHODS: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. RESULTS: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. CONCLUSIONS: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. METHODS: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. FINDINGS: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. INTERPRETATION: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. FUNDING: The Netherlands Organization for Health Research and Development.

Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

BACKGROUND: This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. METHODS: This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival. RESULTS: Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001). CONCLUSION: Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.

Evolution of surgical approach to rectal cancer resection: A multinational registry assessment.

PURPOSE: Surgical approach to rectal cancer has evolved in recent decades, with introduction of minimally invasive surgery (MIS) techniques and local excision. Since implementation might differ internationally, this study is aimed at evaluating trends in surgical approach to rectal cancer across different countries over the last 10 years and to gain insight into patient, tumour and treatment characteristics. METHODS: Pseudo-anonymised data of patients undergoing resection for rectal cancer between 2010 and 2019 were extracted from clinical audits in the Netherlands (NL), Sweden (SE), England-Wales (EW) and Australia-New Zealand (AZ). RESULTS: Ninety-nine thousand five hundred ninety-seven patients were included (38,413 open, 55,155 MIS and 5416 local excision). An overall increase in MIS was observed from 29.9% in 2010 to 72.1% in 2019, with decreasing conversion rates (17.5-9.0%). The MIS proportion was highly variable between countries in the period 2010-2014 (54.4% NL, 45.3% EW, 39.8% AZ, 14.1% SE, P < 0.001), but variation reduced over time (2015-2019 78.8% NL, 66.3% EW, 64.3% AZ, 53.2% SE, P < 0.001). The proportion of local excision for the two periods was highly variable between countries: 4.7% and 11.8% in NL, 3.9% and 7.4% in EW, 4.7% and 4.6% in AZ, 6.0% and 2.9% in SE. CONCLUSIONS: Application and speed of implementation of MIS were highly variable between countries, but each registry demonstrated a significant increase over time. Local excision revealed inconsistent trends over time.

Long-term restoration of bowel continuity after rectal cancer resection and the influence of surgical technique: A nationwide cross-sectional study.

AIM: Literature on nationwide long-term permanent stoma rates after rectal cancer resection in the minimally invasive era is scarce. The aim of this population-based study was to provide more insight into the permanent stoma rate with interhospital variability (IHV) depending on surgical technique, with pelvic sepsis, unplanned reinterventions and readmissions as secondary outcomes. METHOD: Patients who underwent open or minimally invasive resection of rectal cancer (lower border below the sigmoid take-off) in 67 Dutch centres in 2016 were included in this cross-sectional cohort study. RESULTS: Among 2530 patients, 1470 underwent a restorative resection (58%), 356 a Hartmann's procedure (14%, IHV 0%-42%) and 704 an abdominoperineal resection (28%, IHV 3%-60%). Median follow-up was 51 months. The overall permanent stoma rate at last follow-up was 50% (IHV 13%-79%) and the unintentional permanent stoma rate, permanent stoma after a restorative procedure or an unplanned Hartmann's procedure, was 11% (IHV 0%-29%). A total of 2165 patients (86%) underwent a minimally invasive resection: 1760 conventional (81%), 170 transanal (8%) and 235 robot-assisted (11%). An anastomosis was created in 59%, 80% and 66%, with corresponding unintentional permanent stoma rates of 12%, 24% and 14% (p = 0.001), respectively. When corrected for age, American Society of Anesthesiologists classification, cTNM, distance to the anorectal junction and neoadjuvant (chemo)radiotherapy, the minimally invasive technique was not associated with an unintended permanent stoma (p = 0.071) after a restorative procedure. CONCLUSION: A remarkable IHV in the permanent stoma rate after rectal cancer resection was found. No beneficial influence of transanal or robot-assisted laparoscopy on the unintentional permanent stoma rate was found, although this might be caused by the surgical learning curve. A reduction in IHV and improving preoperative counselling for decision-making for restorative procedures are required.

Patient preferences for active surveillance vs standard surgery after neoadjuvant chemoradiotherapy in oesophageal cancer treatment: The NOSANO-study.

Active surveillance may be a safe and effective treatment in oesophageal cancer patients with a clinically complete response after neoadjuvant chemoradiotherapy (nCRT). In the NOSANO-study we gained insight in patients' motive to opt for either an experimental treatment called active surveillance or for standard immediate surgery. Both qualitative and quantitative analyses methods were used. Forty patients were interviewed about their treatment preference, 3 months after completion of nCRT (T1). Data were recorded, transcribed verbatim and analysed according to the principles of grounded theory. In addition, at T1 and T2 (12 months after completion of nCRT) questionnaires on health-related quality of life, coping, anxiety and decisional regret (only T2) were administered. Interview data analyses resulted in a conceptual model with 'dealing with threat of cancer' as the central theme. Patients preferring active surveillance tend to cope with this threat by confiding in their bodies and good outcomes. Their mind-set is one of 'enjoy life now'. Patients preferring surgery tend to cope by minimizing uncertainty and eliminating the source of cancer. Their mind-set is one of 'don't give up, act now'. Furthermore, questionnaire results showed that patients with a preference for standard surgery had a lower quality of life. Patient preferences are individualized and thus difficult to predict. Our model can help healthcare professionals to determine patient preferences for treatment. Coping style and mind-set seem to be determining factors here.

Trends in Distal Esophageal and Gastroesophageal Junction Cancer Care: The Dutch Nationwide Ivory Study.

OBJECTIVE: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer. SUMMARY OF BACKGROUND DATA: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer. METHODS: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods. RESULTS: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% ( P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027). CONCLUSION: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

One Decade of Declining Use of Defunctioning Stomas After Rectal Cancer Surgery in the Netherlands: Are We on the Right Track?

BACKGROUND: The beneficial effect of a defunctioning stoma in mitigating the consequences of anastomotic leakage after rectal cancer surgery is still debated. OBJECTIVE: This study aims to reflect on a decade of rectal cancer surgery in terms of stoma construction and anastomotic leakage. DESIGN: Retrospective observational study. SETTING: This study used data from the Dutch Colorectal Audit from 2011 to 2020. PATIENTS: Patients undergoing rectal cancer surgery with a primary anastomosis. MAIN OUTCOME MEASURES: Primary outcome was anastomotic leakage. Secondary outcomes were minor complications, admission to intensive care, length of stay, readmission, and patient death. RESULTS: A total of 13,263 patients were included in this study. A defunctioning stoma was constructed in 7106 patients (53.6%). Patients with a defunctioning stoma were less likely to develop anastomotic leakage (7.9% vs 13.0%), and if anastomotic leakage occurred, fewer patients needed surgical reintervention (37.7% vs 81.1%). An annual decrease in the construction of a defunctioning stoma was seen (69.8% in 2011 vs 51.8% in 2015 vs 29.7% in 2020), accompanied by a 5% increase in anastomotic leakage (9.1% in 2011 vs 14.1% in 2020). A defunctioning stoma was associated with a higher occurrence of minor complications, increased admissions to the intensive care unit, longer length of stay, and more readmissions within 90 days. LIMITATION: This retrospective study is susceptible to confounders by indications, and there could be risk factors for anastomotic leakage and the use of a stoma that were not regarded. CONCLUSIONS: The reduction in defunctioning stomas is paralleled with an increase in anastomotic leakage. However, patients with a defunctioning stoma also showed more minor complications, a prolonged length of stay, more intensive care admissions, and more readmissions. In our opinion, the trade-offs of selective use should be individually considered. See Video Abstract at http://links.lww.com/DCR/C137 . UNA DCADA DISMINUYENDO EL USO DE ESTOMAS DISFUNCIONANTES EN LOS CASOS DE CNCER DE RECTO EN HOLANDA ESTAMOS HACIENDO LO CORRECTO: ANTECEDENTES:Aún se debate el efecto benéfico de la confección de un estoma disfuncionante para limitar las consecuencias de la fuga anastomótica en los casos de cirugía por cáncer de recto.OBJETIVO:Reflexiones sobre una década de cirugía por cáncer de recto en términos de confección de estomas y de fugas anastomóticas.DISEÑO:Estudio retrospectivo y observacional.AJUSTE:El presente estudio utilizó datos de la Auditoría Colorectal Holandesa entre 2011 y 2020.PACIENTES:Todos aquellos intervenidos por cáncer de recto con anastomosis primaria.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue evaluar la fuga anastomótica. Los resultados secundarios fueron las complicaciones menores, la permanencia en cuidados intensivos, la duración de la hospitalización, las rehospitalizaciones y las causas de muerte en los pacientes.RESULTADOS:Un total de 13.263 pacientes fueron incluidos en el presente estudio. Se confeccionó un estoma disfuncionante en 7.106 (53,6%) pacientes. Aquellos portadores de un estoma disfuncionante tenían menos probabilidades de desarrollar una fuga anastomótica (7,9 % frente a 13,0 %) y, si ocurría una fuga anastomótica, menos pacientes necesitaban reintervención quirúrgica (37,7 % frente a 81,1 %). Se observó una disminución anual en la confección de un estoma disfuncionante (69,8 % en 2011 frente a 51,8 % en 2015 frente a 29,7 % en 2020), acompañada de un aumento del 5 % en la fuga anastomótica (9,1 % en 2011 frente a 14,1 % en 2020). Un estoma disfuncionante se asoció con una mayor incidencia de complicaciones menores, permanencia en la unidad de cuidados intensivos, una estadía más prolongada y más rehospitalizaciones dentro de los 90 días.LIMITACIÓN:Estudio retrospectivo susceptible de factores de confusión según las indicaciones, donde podrían no haber sido considerados ciertos factores de riesgo con relación a la fuga anastomótica y a la confección de un estoma disfuncionante.CONCLUSIÓN:La reducción de estomas disfuncionantes es paralela con el aumento de la fuga anastomótica. Sin embargo, los pacientes con un estoma disfuncionante también mostraron más complicaciones menores, una estadía prolongada, más admisiones a cuidados intensivos y más rehospitalizaciones. En nuestra opinión, las ventajas y desventajas del uso selectivo de estomas disfuncionantes deben ser consideradas caso por caso. Consulte Video Resumen en https://links.lww.com/DCR/C137 . (Traducción-Dr. Xavier Delgadillo ).

Short- and Long-term Outcomes After Laparoscopic Emergency Resection of Left-Sided Obstructive Colon Cancer: A Nationwide Propensity Score-Matched Analysis.

BACKGROUND: The role of laparoscopy for emergency resection of left-sided obstructive colon cancer remains unclear, especially regarding impact on survival. OBJECTIVE: This study aimed to determine short- and long-term outcomes after laparoscopic versus open emergency resection of left-sided obstructive colon cancer. DESIGN: This observational cohort study compared patients who underwent laparoscopic emergency resection to those who underwent open emergency resection between 2009 and 2016 by using 1:3 propensity-score matching. Matching variables included sex, age, BMI, ASA score, previous abdominal surgery, tumor location, cT4, cM1, multivisceral resection, small-bowel distention on CT, and subtotal colectomy. SETTING: This was a nationwide, population-based study. PATIENTS: Of 2002 eligible patients with left-sided obstructive colon cancer, 158 patients who underwent laparoscopic emergency resection were matched with 474 patients who underwent open emergency resection. INTERVENTIONS: The intervention was laparoscopic versus open emergency resection. MAIN OUTCOME MEASURES: The main outcome measures were 90-day mortality, 90-day complications, permanent stoma, disease recurrence, overall survival, and disease-free survival. RESULTS: Intentional laparoscopy resulted in significantly fewer 90-day complications (26.6% vs 38.4%; conditional OR, 0.59; 95% CI, 0.39-0.87) and similar 90-day mortality. Laparoscopy resulted in better 3-year overall survival (81.0% vs 69.4%; HR, 0.54; 95% CI, 0.37-0.79) and disease-free survival (68.3% vs 52.3%; HR, 0.64; 95% CI, 0.47-0.87). Multivariable regression analyses of the unmatched 2002 patients confirmed an independent association of laparoscopy with fewer 90-day complications and better 3-year survival. LIMITATIONS: Selection bias was the limitation that cannot be completely ruled out because of the retrospective nature of this study. CONCLUSIONS: This population-based study with propensity score-matched analysis suggests that intentional laparoscopic emergency resection might improve outcomes in patients with left-sided obstructive colon cancer compared to open emergency resection. Management of those patients in the emergency setting requires proper selection for intentional laparoscopic resection if relevant expertise is available, thereby considering other alternatives to avoid open emergency resection (ie, decompressing stoma). See Video Abstract at http://links.lww.com/DCR/B972 . RESULTADOS A CORTO Y LARGO PLAZO DESPUS DE LA RESECCIN LAPAROSCPICA DE EMERGENCIA EN CNCER DE COLON IZQUIERDO OBSTRUCTIVO UN ANLISIS EMPAREJADO POR PUNTAJE DE PROPENSIN A NIVEL NACIONAL: ANTECEDENTES:El papel de la laparoscopia en la resección de emergencia en cáncer de colon izquierdo obstructivo sigue sin estar claro, especialmente con respecto al impacto en la supervivencia.OBJETIVO:El objetivo de este estudio fue determinar los resultados a corto y largo plazo después de la resección de emergencia laparoscópica versus abierta en cáncer de colon izquierdo obstructivo.DISEÑO:Estudio observacional de cohortes comparó pacientes que se sometieron a resección de laparoscópica de emergencia versus resección abierta de emergencia entre 2009 y 2016, mediante el uso de emparejamineto por puntaje de propensión 1: 3. Las variables emparejadas incluyeron sexo, edad, IMC, puntaje ASA, cirugía abdominal previa, ubicación del tumor, cT4, cM1, resección multivisceral, distensión del intestino delgado en la TAC y colectomía subtotal.ENTORNO CLINICO:A nivel nacional, basado en la población.PACIENTES:De 2002 pacientes elegibles con cáncer de colon izquierdo obstructivo, 158 pacientes con resección laparoscópica s de emergencia e emparejaron con 474 pacientes con resección abierta de emergencia.INTERVENCIONES:Resección laparoscópica de emergencia versus abierta.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la mortalidad a 90 días, complicaciones a 90 días, estoma permanente, recurrencia de la enfermedad, supervivencia general y supervivencia libre de enfermedad.RESULTADOS:La laparoscopia intencional dió como resultado significativamente menos complicaciones a los 90 días (26,6 % vs 38,4 %, cOR 0,59, IC del 95 %: 0,39-0,87) y una mortalidad similar a los 90 días. La laparoscopia resultó en una mejor supervivencia general a los 3 años (81,0 % vs 69,4 %, HR 0,54, IC del 95 % 0,37-0,79) y supervivencia libre de enfermedad (68,3 % vs 52,3 %, HR 0,64, IC del 95 % 0,47-0,87). Los análisis de regresión multivariable de los 2002 pacientes no emparejados confirmaron una asociación independiente de la laparoscopia con menos complicaciones a los 90 días y una mejor supervivencia a los 3 años.LIMITACIONES:El sesgo de selección no se puede descartar por completo debido a la naturaleza retrospectiva de este estudio.CONCLUSIONES:Estudio poblacional con análisis emparejado por puntaje de propensión sugiere que la resección laparoscópica de emergencia intencional podría mejorar los resultados a corto y largo plazo en pacientes con cáncer de colon izquierdo obstructivo en comparación con resección abierta de emergencia, lo que justifica la confirmación en estudios futuros. El manejo de esos pacientes en el entorno de emergencia requiere una selección adecuada para la resección laparoscópica intencional si se dispone de experiencia relevante, considerando así otras alternativas para evitar la resección abierta de emergencia (es decir, ostomia descompresiva). Consulte Video Resumen en http://links.lww.com/DCR/B972 . (Traducción- Dr. Francisco M. Abarca-Rendon & Dr. Fidel Ruiz Healy).

Uptake of robot-assisted colon cancer surgery in the Netherlands.

BACKGROUND: The robot-assisted approach is now often used for rectal cancer surgery, but its use in colon cancer surgery is less well defined. This study aims to compare the outcomes of robotic-assisted colon cancer surgery to conventional laparoscopy in the Netherlands. METHODS: Data on all patients who underwent surgery for colon cancer from 2018 to 2020 were collected from the Dutch Colorectal Audit. All complications, readmissions, and deaths within 90 days after surgery were recorded along with conversion rate, margin and harvested nodes. Groups were stratified according to the robot-assisted and laparoscopic approach. RESULTS: In total, 18,886 patients were included in the analyses. The operative approach was open in 15.2%, laparoscopic in 78.9% and robot-assisted in 5.9%. The proportion of robot-assisted surgery increased from 4.7% in 2018 to 6.9% in 2020. There were no notable differences in outcomes between the robot-assisted and laparoscopic approach for Elective cT1-3M0 right, left, and sigmoid colectomy. Only conversion rate was consistently lower in the robotic group. (4.6% versus 8.8%, 4.6% versus 11.6%, and 1.6 versus 5.9%, respectively). CONCLUSIONS: This nationwide study on surgery for colon cancer shows there is a gradual but slow adoption of robotic surgery for colon cancer up to 6.9% in 2020. When comparing the outcomes of right, left, and sigmoid colectomy, clinical outcomes were similar between the robotic and laparoscopic approach. However, conversion rate is consistently lower in the robotic procedures.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

OBJECTIVE: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. BACKGROUND: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. METHODS: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. RESULTS: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84). CONCLUSIONS: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

Stoma versus anastomosis after sphincter-sparing rectal cancer resection; the impact on health-related quality of life.

BACKGROUND: Surgical resection is the mainstay of curative treatment for rectal cancer. Post-operative complications, low anterior resection syndrome (LARS), and the presence of a stoma may influence the quality of life after surgery. This study aimed to gain more insights into the long-term trade-off between stoma and anastomosis. METHODS: All patients who underwent sphincter-sparing surgical resection for rectal cancer in the Leiden University Medical Center and the Reinier de Graaf Gasthuis between January 2012 and January 2016 were included. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, EQ-5D-5L, and the LARS score. A comparison was made between patients with a stoma and without a stoma after follow-up. RESULTS: Some 210 patients were included of which 149 returned the questionnaires (70.9%), after a mean follow-up of 3.69 years. Overall quality of life was not significantly different in patients with and without stoma after follow-up using the EORTC-QLQ-C30 (p = 0.15) or EQ-5D-5L (p = 0.28). However, after multivariate analysis, a significant difference was found for the presence of a stoma on global health status (p = 0.01) and physical functioning (p < 0.01). Additionally, there was no difference detected in the quality of life between patients with major LARS or a stoma. CONCLUSION: This study shows that after correction for possible confounders, a stoma is associated with lower global health status and physical functioning. However, no differences were found in health-related quality of life between patients with major LARS and patients with a stoma. This suggests that the choice between stoma and anastomosis is mainly preferential and that shared decision-making is required.

Multicenter cohort study on the presentation and treatment of acute appendicitis during the COVID-19 pandemic.

PURPOSE: Current studies have demonstrated conflicting results regarding surgical care for acute appendicitis during the COVID-19 pandemic. This study aimed to assess trends in diagnosis as well as treatment of acute appendicitis in the Netherlands during the first and second COVID-19 infection wave. METHODS: All consecutive patients that had an appendectomy for acute appendicitis in nine hospitals from January 2019 to December 2020 were included. The primary outcome was the number of appendectomies for acute appendicitis. Secondary outcomes included time between onset of symptoms and hospital admission, proportion of complex appendicitis, postoperative length of stay and postoperative infectious complications. Outcomes were compared between the pre-COVID group and COVID group. RESULTS: A total of 4401 patients were included. The mean weekly rate of appendectomies during the COVID period was 44.0, compared to 40.9 in the pre-COVID period. The proportion of patients with complex appendicitis and mean postoperative length of stay in days were similar in the pre-COVID and COVID group (respectively 35.5% vs 36.8%, p = 0.36 and 2.0 ± 2.2 vs 2.0 ± 2.6, p = 0.93). There were no differences in postoperative infectious complications. A computed tomography scan was used more frequently as a diagnostic tool after the onset of COVID-19 compared to pre-COVID (13.8% vs 9.8%, p < 0.001, respectively). CONCLUSION: No differences were observed in number of appendectomies, proportion of complex appendicitis, postoperative length of stay or postoperative infectious complications before and during the COVID-19 pandemic. A CT scan was used more frequently during the COVID-19 pandemic.

Outcomes After Major Surgical Procedures in Octogenarians: A Nationwide Cohort Study.

INTRODUCTION: Aging of the worldwide population has been observed, and postoperative outcomes could be worse in elderly patients. This nationwide study assessed trends in number of surgical resections in octogenarians regarding various major surgical procedures and associated postoperative outcomes. METHODS: All patients who underwent surgery between 2014 and 2018 were included from Dutch nationwide quality registries regarding esophageal, stomach, pancreas, colorectal liver metastases, colorectal cancer, lung cancer and abdominal aortic aneurysms (AAA). For each quality registry, the number of patients who were 80 years or older (octogenarians) was calculated per year. Postoperative outcomes were length of stay (LOS), 30 day major morbidity and 30 day mortality between octogenarians and younger patients. RESULTS: No increase in absolute number and proportion of octogenarians that underwent surgery was observed. Median LOS was higher in octogenarians who underwent surgery for colorectal cancer, colorectal liver metastases, lung cancer, pancreatic disease and esophageal cancer. 30 day major morbidity was higher in octogenarians who underwent surgery for colon cancer, esophageal cancer and elective AAA-repair. 30 day mortality was higher in octogenarians who underwent surgery for colorectal cancer, lung cancer, stomach cancer, pancreatic disease, esophageal cancer and elective AAA-repair. Median LOS decreased between 2014 and 2018 in octogenarians who underwent surgery for stomach cancer and colorectal cancer. 30 day major morbidity decreased between 2014 and 2018 in octogenarians who underwent surgery for colon cancer. No trends were observed in octogenarians regarding 30 day mortality between 2014 and 2018. CONCLUSION: No increase over time in absolute number and proportion of octogenarians that underwent major surgery was observed in the Netherlands. Postoperative outcomes were worse in octogenarians.

Risks and benefits of dermatological machine learning health care applications-an overview and ethical analysis.

BACKGROUND: Visual data are particularly amenable for machine learning techniques. With clinical photography established for skin surveillance and documentation purposes as well as progress checks, dermatology is an ideal field for the development and application of emerging machine learning health care applications (ML-HCAs). To date, several ML-HCAs have detected malignant skin lesions on par with experts or found overlooked visual patterns that correlate with certain dermatological diseases. However, it is well established that ML-HCAs come with ethical and social implications. OBJECTIVES: Currently, there is a lack of research that establishes model design, training, usage and regulation of such technologies sufficient to ensure ethically and socially responsible development and clinical translation, specifically within the field of dermatology. With this paper, we aim to give an overview of currently discussed ethical issues relating to dermatological ML-HCAs. METHODS: On the basis of a thematic, keyword-based literature search, we performed an ethical analysis against established frameworks of biomedical ethics. We combined our results with current, relevant normative machine learning ethics literature to identify the status quo of the ethics of ML-HCAs in dermatology. We describe the benefits and risks of dermatological ML-HCAs that are currently being developed for clinical purposes. RESULTS: The potential benefits range from better patient outcomes to better knowledge accessibility to decreasing health care disparities, that is, standards of care between different population groups. The risks associated with ML-HCAs range from confidentiality issues to individual patient outcomes as well as the exacerbation of prevalent health care disparities. We discuss the practical implications for all stages of dermatological ML-HCA development. CONCLUSION: We found that ML-HCAs present stakeholder-specific risks for patients, health care professionals and society, which need to be considered separately. The discipline lacks sufficient biomedical ethics research that could standardize the approach to ML-HCA model design, training, use and regulation of such technologies.

Influence of Minimally Invasive Resection Technique on Sphincter Preservation and Short-term Outcome in Low Rectal Cancer in the Netherlands.

BACKGROUND: Transanal and robotic-assisted total mesorectal excision are techniques that can potentially overcome challenges encountered with a pure laparoscopic approach in patients with rectal cancer. OBJECTIVE: The aim of this study was to evaluate the proportion and predictive factors of restorative procedures and subsequent short-term outcomes of 3 minimally invasive techniques to treat low rectal cancer. DESIGN: This is a nationwide observational comparative registry study. SETTINGS: Patients with rectal cancer were selected from the mandatory Dutch ColoRectal Audit. PATIENTS: Patients with low rectal cancer (≤5 cm) who underwent curative minimally invasive total mesorectal excision between 2015 and 2018 were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the proportion of restorative procedure, positive circumferential resection margin, and postoperative complications. RESULTS: A total of 3466 patients were included for analysis, of which 33% underwent a restorative procedure. Resections were performed laparoscopically in 2845 patients, transanally in 448 patients, and were robot-assisted in 173 patients, with a proportion of restorative procedures of 28%, 66%, and 40%. The transanal approach was independently associated with a restorative procedure (OR, 4.11; 95% CI, 3.21-5.26; p < 0.001). Independent risk factors for a nonrestorative procedure, irrespective of the surgical technique, were age >75 years, ASA physical status ≥3, BMI >30, history of abdominal surgery, clinical T4-stage, mesorectal fascia ≤1 mm, neoadjuvant therapy, and having a procedure in 2015 to 2016 versus 2017 to 2018. The circumferential resection margin involvement was similar for all 3 groups (5.4%, 5.1%, and 5.1%). Short-term postoperative complications were less favorable for the newer techniques than for the laparoscopic approach. LIMITATIONS: This study was limited because of the registry's variables and different group sizes. CONCLUSION: Patients with low rectal cancer in the Netherlands are more likely to receive a restorative procedure with a transanal approach, compared with a laparoscopic or robotic procedure. Short-term oncological outcomes are comparable between the 3 minimally invasive techniques. See Video Abstract at http://links.lww.com/DCR/B608. INFLUENCIA DE LA TCNICA DE RESECCIN MINIMAMENTE INVASIVA CON PRESERVACIN DE ESFNTERES EN LA RESOLUCIN A CORTO PLAZO EN CANCER DE TERCIO INFERIOR DE RECTO EN LOS PASES BAJOS: ANTECEDENTES:La excisión mesorrectal transanal y asistida por robot son técnicas que potencialmente pueden superar algunos obstáculos que podemos encontrar en un abordaje exclusivamente laparoscópico en pacientes con cáncer de recto.OBJECTIVOS:El objetivo de este estudio es evaluar la proporción y los factores de predicción positivos de los procedimientos restauradores y los resultados subsecuentes a corto plazo de tres técnicas mínimamente invasivas para tratar el cáncer de tercio inferior de recto.DISEÑO:Es un estudio comparativo observacional del registro nacional.ESCENARIO:Pacientes con cáncer de recto seleccionados del Registro Oficial de la Auditoría Holandesa Colo-rectal.PACIENTGES:Pacientes con cáncer de tercio inferior de recto (≤5 centimetros) sometidos a excision mesorrectal total mínimamente invasiva curativa.PRINCIPALES PARAMETROS DE EFECTIVIDAD:Proporción de procedimientos restauradores, margen de resección circunferencial positivo y complicaciones postoperatorias.RESULTADOS:Se incluyeron un total de 3,466 pacientes para análisis, de los cuales 33% fueron sometidos a procedimiento restaurador. Las resecciones fueron laparoscópica en 2,845 pacientes, transanal en 448 y asistidas por robot en 173, con una proporción de procedimientos restauradores en 28%, 66% y 40% respectivamente. El abordaje transanal se correlacionó en forma independiente con el procedimiento restaurador (OR 4.11; 95% CI 4.11; 95% CI 3.21-5.26; p<0.001). Los factores de riesgo independientes para un procedimiento no restaurador, sin tomar en cuenta la técnica quirúrgica fueron: edad >75, American Society of Anesthesiologist ≥3, índice de masa corporal >30, antecedente de cirugía abdominal, Estadio clínico T4, fascia mesorrectal ≤1 millimetro, terapia neoadyuvante y haber sido sometido al procedimiento en 2015-2016 y no en 2017-2018. El margen circunferencial de resección involucrado fue similar para los tres grupos (5.4%, 5.1% y 5.1%). Las complicaciones postquirúrgicas a corto plazo fueron menos favorables para las técnicas nuevas comparadas con el abordaje laparoscópico.LIMTANTES:El estudio tiene la limitación de las variables dependientes del registro y la diferencia entre el número de pacientes en cada grupo.CONCLUSION:Los pacientes con cáncer de tercio inferior de recto en Holanda se tratan con mayor frecuencia mediante un procedimiento restaurador transanal en comparación con los abordajes laparoscópico o robótico. Los resultados favorables desde el punto de vista oncológico a corto plazo son comparables entre las tres técnicas de invasión mínima. Consulte Video Resumenhttp://links.lww.com/DCR/B608.

Time interval between rectal cancer resection and reintervention for anastomotic leakage and the impact of a defunctioning stoma: A Dutch population-based study.

AIM: In the Netherlands, a selective policy of faecal diversion after rectal cancer surgery is generally applied. This study aimed to evaluate the timing, type, and short-term outcomes of reoperation for anastomotic leakage after primary rectal cancer resection stratified for a defunctioning stoma. METHOD: Data of all patients who underwent primary rectal cancer surgery with primary anastomosis from 2013-2019 were extracted from the Dutch ColoRectal Audit. Primary outcomes were new stoma construction, mortality, ICU admission, prolonged hospital stay, and readmission. RESULTS: In total, 10,772 rectal cancer patients who underwent surgery with primary anastomosis were included, of whom 46.6% received a primary defunctioning stoma. The reintervention rate for anastomotic leakage was 8.2% and 11.6% for patients with and without a defunctioning stoma (p < 0.001). Reintervention consisted of reoperation in 44.0% and 85.3% (p < 0.001), with a median time interval from primary resection to reoperation of seven days (IQR 4-14) vs. five days (IQR 3-13), respectively. In the presence of a defunctioning stoma, early reoperation (<5 days; n = 47) was associated with significantly more end-colostomy construction (51% vs. 33%) and ICU admission (66% vs. 38%) than late reoperation (≥5 days; n = 127). Without defunctioning stoma, early reoperation (n = 252) was associated with significantly higher mortality (4% vs. 1%), and more ICU admissions (52% vs.34%) than late reoperation (n = 302). CONCLUSIONS: Early reoperations after rectal cancer resection are associated with worse outcomes reflected by a more frequent ICU admission in general, more colostomy construction, and higher mortality in patients with primary defunctioned and nondefunctioned anastomosis.

Trends in risk factors of anastomotic leakage after colorectal cancer surgery (2011-2019): A Dutch population-based study.

AIM: Anastomotic leakage (AL) after colon cancer (CC) and rectal cancer (RC) surgery often requires reintervention. Prevalence and morbidity may change over time with evolutions in treatment strategies and changes in patient characteristics. This nationwide study aimed to evaluate changes in the incidence, risk factors and mortality from AL during the past nine years. METHODS: Data of CC and RC resections with primary anastomosis were extracted from the Dutch Colorectal Audit (2011-2019). AL was registered if requiring reintervention. Three consecutive cohorts were compared using logistic regression analysis. RESULTS: Incidence of AL after CC surgery decreased from 6.6% in 2011-2013 to 4.8% in 2017-2019 and increased from 8.6% to 11.9% after RC surgery. In 2011-2013, male sex, ASA ≥3, (y)pT3-4, neoadjuvant therapy, emergency surgery and multivisceral resection were identified as risk factors for AL after CC surgery. In 2017-2019, only male sex and ASA ≥3 were risk factors for AL. For RC patients, male sex and neoadjuvant therapy were a risk factor for AL in 2011-2013. In 2017-2019, transanal approach was also a risk factor for AL. Postoperative mortality rate after AL was 12% (CC) and 2% (RC) in 2017-2019, without significant changes over time. CONCLUSION: Contradictory trends in incidence and mortality for AL were observed among CC and RC surgery with changing risk factors over the past 9 years. High mortality after AL is only observed after CC surgery and remains unchanged. Continued efforts should be made to improve early detection and treatment of AL for these patients.

Transition from laparoscopic to robotic rectal resection: outcomes and learning curve of the initial 100 cases.

BACKGROUND: Following several landmark trials, laparoscopic rectal resection has reached standard clinical practice. Current literature is undecided on the advantages of robotic rectal resection and little is known on its learning curve. This study aimed to compare the outcomes of the first 100 robotic rectal resections to the laparoscopic approach in a teaching hospital experienced in laparoscopic colorectal surgery. METHODS: A retrospective analysis was conducted of a prospective cohort of all consecutive rectal resections between January 2012 and September 2019 at a single center. All laparoscopic cases were compared to the robotic approach. Outcomes included operative time, morbidity, anastomotic leakage, and hospital stay. RESULTS: Out of the 326 consecutive resections, 100 were performed robotically and 220 laparoscopically, the remaining 6 open cases were excluded. Median operative time was lower for robotic cases (147 (121-167) versus 162 (120-218) minutes P = 0.024). Overall morbidity was lower in robotic cases (25% versus 50%, P < 0.001), while major morbidity was similar. Anastomotic leakage was observed in 11% (8/70) of robotic and 15% (18/120) of laparoscopic anastomoses, despite more anastomoses in the robotic group (70%, 70/100 versus 55%, 120/220, P = 0.001). Median length of stay was 4 (4-7) days after a robotic and 6 (5-9) days after a laparoscopic procedure. DISCUSSION: Implementation of a robotic rectal resection program in an experienced laparoscopic surgery center was associated with reduced operative time, length of stay, and fewer complications despite a learning curve.