Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer-evaluation in a nationwide Danish cohort.

BACKGROUND: Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment. Digital PCR (dPCR) offers low analysis costs and turnaround times of less than a day, making it ripe for clinical implementation. Here, we used tumor-informed dPCR for ctDNA detection in a large colorectal cancer (CRC) cohort to evaluate the potential for post-operative risk assessment and serial monitoring, and how the metastatic site may impact ctDNA detection. Additionally, we assessed how altering the ctDNA-calling algorithm could customize performance for different clinical settings. PATIENTS AND METHODS: Stage II-III CRC patients (N = 851) treated with a curative intent were recruited. Based on whole-exome sequencing on matched tumor and germline DNA, a mutational target was selected for dPCR analysis. Plasma samples (8 ml) were collected within 60 days after operation and-for a patient subset (n = 246)-every 3-4 months for up to 36 months. Single-target dPCR was used for ctDNA detection. RESULTS: Both post-operative and serial ctDNA detection were prognostic of recurrence [hazard ratio (HR) = 11.3, 95% confidence interval (CI) 7.8-16.4, P < 0.001; HR = 30.7, 95% CI 20.2-46.7, P < 0.001], with a cumulative ctDNA detection rate of 87% at the end of sample collection in recurrence patients. The ctDNA growth rate was prognostic of survival (HR = 2.6, 95% CI 1.5-4.4, P = 0.001). In recurrence patients, post-operative ctDNA detection was challenging for lung metastases (4/21 detected) and peritoneal metastases (2/10 detected). By modifying the cut-off for calling a sample ctDNA positive, we were able to adjust the sensitivity and specificity of our test for different clinical contexts. CONCLUSIONS: The presented results from 851 stage II-III CRC patients demonstrate that our personalized dPCR approach effectively detects MRD after operation and shows promise for serial ctDNA detection for recurrence surveillance. The ability to adjust sensitivity and specificity shows exciting potential to customize the ctDNA caller for specific clinical settings.

Culture media affect sex after IVF treatment-a detailed analysis of explanatory variables.

PURPOSE: The purpose of this study was to provide a detailed analysis of clinical and laboratory factors associated with skewed secondary sex ratio (SSR) after ART. METHOD: Retrospective cohort study of embryos resulting in live births, from frozen and fresh single blastocyst transfers. Embryos were cultured in either G-TL (n = 686) or Sage media (n = 685). Data was analyzed using a multivariate logistic regression model and a mixed model analysis. RESULTS: Significantly more male singletons were born after culture in Sage media compared to G-TL media (odds ratio (OR) 1.34, 95% CI (1.05, 1.70), P = 0.02). Inner cell mass grade B vs A (OR 1.36 95% CI (1.05, 1.76), P = 0.02) and one previous embryo transfer (OR 1.49, 95% CI (1.03, 2.16), P = 0.03) were associated with a significantly higher probability of male child at birth. Factors associated with a reduced probability of male child were expansion grade 3 vs 5 (OR 0.66, 95% CI (10.45, 0.96), P = 0.03) and trophectoderm grade B vs A (OR 0.57, 95% CI (0.44, 0.74), P = 0.00). Male embryos developed significantly faster in Sage media compared to G-TL media for the stages of blastocyst (- 1.12 h, 95% CI (- 2.12, - 0.12)), expanded blastocyst (- 1.35 h, 95% CI (- 2.34, - 0.35)), and hatched blastocyst (- 1.75 h, 95% CI (- 2.99, - 0.52)). CONCLUSION: More male children were born after culture in Sage media compared to G-TL media. Male embryo development was affected by culture media. Our observations suggest that culture media impact male embryo quality selectively, thus potentially favoring the selection of male embryos.

Validation of the Danish Colorectal Cancer Group (DCCG.dk) database - on behalf of the Danish Colorectal Cancer Group.

AIM: The aim of this study was to validate the clinical quality database of the Danish Colorectal Cancer Group. The validation is meant to focus on core data regarding staging of the disease, treatment provided, patient-related factors and key complications. METHOD: This was a database validation study assessing the completeness of the database and the accuracy of the data by re-entering core variables into an online module in a blinded fashion and comparing re-entered data with the original database data. A sample of 5% of patients from the years 2014-2017 was randomly selected. RESULTS: The sample of 936 patients was identified and data were re-entered. The completeness of the data retrieved was a median of 96%, 100% and 99% for preoperative, intra-operative and postoperative variables, respectively. The overall accuracy was a median of 95%. The least accurate variable was date of diagnosis (50% perfect agreement), with agreement rising to 96% when near matches defined as correct date ± 30 days were included. Intra-operative variables were of high quality, as were data on surgical complications including anastomotic leakage, where agreement was 97%. CONCLUSION: This was the first major validation of the Danish Colorectal Cancer Group's database. Overall, the completeness and quality of data were high, but the validation process also identified weaknesses, which can be crucial for future users to acknowledge and consider.

Preadmission use of antidepressants and risk of complications and death after colorectal cancer surgery: a nationwide population-based cohort study.

AIM: Few studies have evaluated how preadmission use of antidepressants affects outcomes in colorectal cancer (CRC) patients after they have undergone surgery. Therefore, our aim is to examine whether preadmission use of antidepressants increased the risk of complications and death in patients who underwent CRC surgery. METHOD: Using the Danish Colorectal Cancer Group Database we identified patients who underwent CRC surgery in Denmark from 2005 to 2012. We identified prescriptions for antidepressants redeemed within 1 year prior to surgery and categorized patients as current users (≤ 90 days), former users (91-365 days) and nonusers. All patients were followed from surgery to 30 days thereafter or to death. We calculated 30-day rates of complications, intensive care unit (ICU) admission and mortality and compared these between users and nonusers using logistic and Cox regression adjusting for potential confounders. RESULTS: Of 27 374 patients, 8.9% were current users and 3.0% were former users. Antidepressant users were older and had more comorbidity but a similar cancer stage. Compared with nonusers, current users had a higher risk of postoperative reoperation [adjusted odds ratio (aORs) = 1.15 (95% CI 1.02-1.30)], medical complications [aORs = 1.41 (95% CI 1.25-1.60)] and increased ICU admission rate [adjusted hazard ratio (aHR) = 1.32 (95% CI 1.21-1.45)]. The 30-day mortality was 11.4% for current users, 9.1% for former users and 6.2% for nonusers [aHR = 1.34 (95% CI 1.17-1.53) for current vs nonusers]. CONCLUSION: Patients with preadmission use of antidepressants had a higher risk of complications and ICU admission, and higher 30-day mortality following CRC surgery than nonusers.

Pelvic insufficiency fractures frequently occur following preoperative chemo-radiotherapy for rectal cancer - a nationwide MRI study.

AIM: The aim of this prospective case-control study was to evaluate the rate of pelvic insufficiency fractures (PIFs) in Denmark using MRI at the 3-year follow-up. All patients had rectal cancer and had undergone surgery with or without preoperative chemo-radiotherapy (CRT). METHOD: Patients registered with primary rectal cancer in the Danish Colorectal Cancer Group database, who underwent rectal cancer resection from April 2011 through August 2012, were invited to participate in a national MRI study aiming to detect local recurrence and evaluate quality of the surgical treatment. Pelvic MRI including bone-specific sequences 3 years after treatment was obtained. The primary outcome was the rate of PIFs; secondary outcome was risk factors of PIFs evaluated in multivariate analysis. RESULTS: During the study period, 890 patients underwent rectal cancer surgery. Of these, 403 patients were included in the MRI study and had a 3-year follow-up MRI. PIFs were detected in 49 (12.2%; 95% CI 9.0-15.4) patients by MRI. PIFs were detected in 39 patients (33.6%; 95% CI 24.9-42.3) treated with preoperative CRT compared to 10 (3.5%; 95% CI 1.3-5.6) non-irradiated patients (P < 0.001). In a multivariate analysis female gender (OR = 3.52; 95% CI 1.7-7.5), age above 65 years (OR = 3.20; 95% CI 1.5-6.9) and preoperative CRT (OR = 14.20; 95% CI 6.1-33.1) were significant risk factors for PIFs. CONCLUSION: Preoperative CRT in the treatment of rectal cancer was associated with a 14-fold higher risk of PIFs after 3 years, whereas female gender and age above 65 years each tripled the risk of PIFs.

Syncytin-1 and its receptor is present in human gametes.

MAIN PURPOSE AND RESEARCH QUESTION: To determine whether the true fusogen Syncytin-1 and its receptor (ASCT-2) is present in human gametes using qRT-PCR, immunoblotting and immunofluorescence. METHODS: Donated oocytes and spermatozoa, originating from a fertility center in tertiary referral university hospital, underwent qRT-PCR, immunoblotting and immunofluorescence analyzes. RESULTS: Quantitative RT-PCR of sperm samples from sperm donors showed that syncytin-1 is present in all samples, however, protein levels varied between donors. Syncytin-1 immunoreactivity predominates in the sperm head and around the equatorial segment. The receptor ASCT-2 is expressed in the acrosomal region and in the sperm tail. Moreover, ASCT-2, but not syncytin-1, is expressed in oocytes and the mRNA level increases with increasing maturity of the oocytes. CONCLUSIONS: Syncytin and its receptor are present in human gametes and localization and temporal appearance is consistent with a possible role in fusion between oocyte and sperm.

Inter-fraction motion robustness in a prospective phase II trial on dose-escalated proton reirradiation for locally recurrent rectal cancer.

Background and purpose: Intensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC). Materials and methods: The inter-fraction motion robustness was assessed for the initial twelve patients enrolled in the ReRad-II study. Patients with resectable LRRC were assessed for neoadjuvant IMPT (55 Gy(RBE)/44Fx) and unresectable recurrences for definitive IMPT (57.5-65 Gy(RBE)/ 46-52Fx). Target coverage and dose to OAR were assessed for robustly optimised three-field IMPT, on 12 plan computerized tomography (CT) scans (pCT) - and 47 repetitive control CT scans (cCTs) during the treatment. The target coverage and doses to OAR were re-calculated on each cCT and the mean dose ratio (pCT/cCT-ratio) and target coverage (V95%) was evaluated. Results: The target coverage was robust with a mean dose pCT/cCT-ratio of 1.00 (+/-1%). The V95% target coverage for every cCT were above the accepted worst-case scenario in the robust evaluation. Considerable variation in bladder-, bowel bag-, and bowel loop volume was observed. The OAR with the largest variation in ratio was the bladder (pCT/cCT-ratio: 1.3 (range: 0.5-4.7). Conclusions: IMPT for dose-escalated reirradiation of LRRC provided anatomically robust target coverage despite OAR changes. Inter-fraction motion resulted in OAR doses varying within clinically acceptable range.

Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study.

BACKGROUND: It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions. METHODS: We conducted a cohort study (1995-2010) of all Danish CRC patients (n=56963), and five times as many persons from the general population (n=271670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities. RESULTS: Among CRC patients with a CCI score=1, the 0-1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis. CONCLUSION: Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.

Value of laparoscopy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis.

BACKGROUND: The outcome of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on the extent of peritoneal carcinomatosis. The role of laparoscopy in the preoperative assessment of extent of peritoneal carcinomatosis in potential candidates for cytoreductive surgery and HIPEC was evaluated in a consecutive series. METHODS: Patients with peritoneal carcinomatosis from colorectal cancer or appendiceal cancer, pseudomyxoma peritonei or peritoneal mesothelioma referred to a single, national HIPEC centre were included prospectively between June 2006 and January 2012. From September 2010, preoperative evaluation also included a laparoscopy in patients deemed amenable to cytoreductive surgery and HIPEC after radiological evaluation, apart from those with pseudomyxoma peritonei with massive amounts of mucin. RESULTS: In the period before laparoscopic evaluation, 70 patients underwent laparotomy of whom 39 (56 per cent) completed cytoreductive surgery and HIPEC. After the introduction of laparoscopic assessment, diagnostic laparoscopy was planned in 45 patients and successful in 43. The laparoscopic evaluation excluded 18 patients from surgery because of extensive disease, among other reasons. Laparoscopy was uneventful and associated with no deaths. Twenty-seven patients were considered amenable to cytoreductive surgery and HIPEC based on laparoscopic findings, of whom 17 completed this treatment; the disease was unresectable in the remaining ten patients. Of 13 patients who were not eligible for laparoscopic evaluation and were subjected to cytoreductive surgery plus HIPEC, 11 completed the procedure. The overall completion rate of cytoreductive surgery and HIPEC increased to 70 per cent (28 of 40) after the introduction of laparoscopic evaluation. CONCLUSION: Diagnostic laparoscopy was valuable in preoperative evaluation of the extent of peritoneal carcinomatosis, and improved patient selection for cytoreductive surgery and HIPEC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: the Danish experience.

AIM: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option with curative intent for selected patients with peritoneal carcinomatosis (PC). CRS and HIPEC have been implemented in Denmark at a single centre since 2006. Six years of data on these patients were analysed. METHOD: Patients with PC from colorectal or appendiceal cancer, pseudomyxoma peritonei or malignant peritoneal mesothelioma referred to the single national HIPEC centre were prospectively registered from June 2006 to July 2012. Morbidity, 30-day mortality and long-term survival of patients who underwent CRS and HIPEC were analysed. RESULTS: In total, 80 patients underwent CRS and HIPEC. PC originated from colorectal cancer in 34 patients, pseudomyxoma peritonei in 29, appendiceal cancer in 13 and malignant peritoneal mesothelioma in four patients. Thirty-two patients had one or more complications during the hospital stay. The 30-day mortality rate was 1.3%. The predicted 2-, 3- and 5-year survival was 60%, 47% and 38% in patients with PC from colorectal cancer, and 100%, 93% and 73% in pseudomyxoma peritonei patients. CONCLUSION: CRS and HIPEC is a safe procedure when centralized as in Denmark. Favourable long-term outcome was achieved in selected patients with PC from colorectal cancer and pseudomyxoma peritonei. Short-term and long-term outcomes were comparable to results from international centres.

Self-expanding metallic stents as bridge to surgery in obstructing colorectal cancer.

BACKGROUND: A self-expanding metallic stent (SEMS) may relieve intestinal obstruction to permit elective resection of colorectal cancer presenting as an emergency. There have been concerns regarding the oncological consequences of this strategy. This study evaluated outcomes in patients with potentially curable colorectal cancer treated with a SEMS as a bridge to surgery. METHODS: This retrospective study included patients with obstructing colorectal cancer in whom a SEMS procedure was attempted between January 2004 and August 2007. Palliative SEMS procedures were excluded. Outcomes for SEMS insertion and subsequent surgery were recorded with a focus on survival. RESULTS: SEMS insertion was attempted and achieved in 34 patients, of whom 30 were discharged after successful relief of obstruction. However, five patients needed acute surgery within 18 days owing to insufficient relief of obstruction (1), or tumour (3) or caecal (1) perforation, with one postoperative death. The remainder underwent elective surgery with no postoperative mortality. In all, 28 of 34 patients were stoma free after operation. The 3-year survival rate of all 34 patients was 74 (95 per cent confidence interval 53 to 86) per cent after a median follow-up of 33·7 months. A curative outcome was achieved in 30 patients. CONCLUSION: Although associated with significant short-term problems, a SEMS can be useful in converting an emergency into an elective situation. No adverse oncological consequences were identified.

Intra-operative perforation is an important predictor of local recurrence and impaired survival after abdominoperineal resection for rectal cancer.

AIM: Abdominoperineal resection for rectal cancer is associated with higher rates of local recurrence and poorer survival than anterior resection. The aim of this study was to evaluate the outcome of conventional abdominoperineal resection in a large national series. METHOD: The study was based on the Danish National Colorectal Cancer Database and included patients treated with abdominoperineal resection between 1 May 2001 and 31 December 2006. Follow up in the departments was supplemented with vital status in the Civil Registration System. The analysis included actuarial local and distant recurrence, and overall and cancer-specific survival. Risk factors for local recurrence, distant metastases, overall survival and cancer-specific survival were identified using multivariate analyses. RESULTS: A total of 1125 patients were followed up for a median of 57 (25-93) months. Intra-operative perforation was reported in 108 (10%) patients. The cumulative 5-year local recurrence rate was 11% [95% confidence interval (CI), 7-13)], overall survival was 56% (95% CI, 53-60) and cancer-specific survival was 68% (95% CI, 65-71). Multivariate analysis showed that perforation, tumour stage and nonradical surgery were independent risk factors for local recurrence; tumour fixation to other organs, perforation and tumour stage were independent risk factors for distant metastases; and risk factors for impaired overall survival and cancer-specific survival were age, tumour perforation, tumour stage, lymph node metastases and nonradical surgery. CONCLUSION: Intra-operative perforation is a major risk factor for local and distant recurrence and survival and therefore should be avoided.

Improved survival after rectal cancer in Denmark.

OBJECTIVE: In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients treated from 1994 to 2006. METHOD: The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. RESULTS: A total of 10 632 patients were operated on. The overall 5-year survival increased from 0.37 in 1994 to 0.51% in 2006; the improvement was greater in men (20% points) than in women (10% points), and greatest in stage III (20% points). The relative 5-year survival increased from 0.46 to 0.62, including an improvement of 23% points in men and 9% points in women and the greatest in stage III (22% points). CONCLUSIONS: The prognosis has improved substantially, probably mainly because of initiatives taken by the DCCG, among which implementation of total mesorectal excision, improved staging and centralized treatment are considered most important.

Seasonal variation in short-term mortality after surgery for colorectal cancer?

OBJECTIVE: Comorbidity has a major impact on short-term and long-term survival of colorectal cancer (CRC) and many CRC patients suffer from comorbidities. Mortality rates for comorbidities like cardio-respiratory diseases exhibit distinct seasonal variations with highest rates in the winter. Therefore, we hypothesized some seasonal variation in 30-day mortality after surgery for CRC as well. METHOD: In a nationwide study, we examined the seasonal pattern in 30-day mortality after surgery for CRC from 1996 to 2006. We identified 33 556 CRC patients in the Danish hospital discharge registries. Monthly 30-day mortality rates were calculated and we constructed a fitted curve of the monthly mortality rates using a periodic regression model. We stratified the analyses for tumour site, urgency of surgery for colon cancer and the level of comorbidity based on American Society of Anaesthesiologists (ASA) score. RESULTS: The overall 30-day mortality was 8.7% [95% confidence interval 8.4-9.0%). Significant seasonal variation in monthly 30-day mortality could not be identified. For colon cancer, a nonsignificant increase was seen in July. An even higher increase in July was observed for CRC patients with moderate or severe comorbidity (ASA score >or= III), but was also nonsignificant. CONCLUSION: Although comorbidity is a well-known negative predictor of short-term survival of CRC, monthly 30-day mortality after surgery for CRC did not exhibit seasonal variation like that observed for comorbid conditions such as cardio-respiratory diseases.

Stoma reversal after intended restorative rectal cancer resection in Denmark: nationwide population-based study.

BACKGROUND: Data on stoma reversal following restorative rectal resection (RRR) with a diverting stoma are conflicting. This study investigated a Danish population-based cohort of patients undergoing RRR to evaluate factors predictive of stoma reversal during 3 years of follow-up. METHODS: Patients from national registries with rectal cancer undergoing RRR or Hartmann's procedure with curative intent between May 2001 and April 2012 were included. Patients with a diverting stoma were followed from the time of primary rectal cancer resection to date of stoma reversal, death, emigration, or end of 3-year follow-up. The cumulative incidence proportion (CIP) of stoma reversal at 1 and 3 years was calculated, treating death as a competing risk. Factors predictive of stoma reversal were explored using Cox regression analysis. RESULTS: Of 6859 patients included, 35·7, 41·9 and 22·4 per cent respectively had a RRR with a diverting stoma, RRR without a stoma, and Hartmann's procedure with an end-colostomy. In patients with a diverting stoma, the CIP of stoma reversal was 70·3 (95 per cent c.i. 68·4 to 72·1) per cent after 1 year, and 74·3 (72·5 to 76·0) per cent after 3 years. Neoadjuvant treatment (hazard ratio (HR) 0·75, 95 per cent c.i. 0·66 to 0·85), blood loss greater than 300 ml (HR 0·86, 0·76 to 0·97), anastomotic leak (HR 0·41, 0·33 to 0·50), T3 category (HR 0·63, 0·47 to 0·83), T4 category (HR 0·62, 0·42 to 0·90) and UICC stage IV (HR 0·57, 0·41 to 0·80) were possible predictors of delayed stoma reversal. CONCLUSION: In one-quarter of the patients the diverting stoma had not been reversed 3 years after the intended RRR procedure.

ANTECEDENTES: Los datos sobre el cierre del estoma (stoma reversal, SR) tras la exéresis el recto con intención reconstructiva (restorative rectal resection, RRR) y estoma derivativo (diverting stoma, DS) son contradictorios. Este estudio analizó los factores predictivos del SR en una cohorte danesa de base poblacional de pacientes sometidos a RRR con un seguimiento de 3 años. MÉTODOS: Los pacientes con cáncer de recto a los que se realizó una RRR o una operación de Hartmann (Hartmann's operation, HO) con intención curativa desde mayo de 2001 hasta abril de 2012, se seleccionaron a partir de registros nacionales. Los pacientes con SD fueron seguidos desde la resección primaria del cáncer rectal hasta la fecha del SR, del fallecimiento, de su cambio de residencia o hasta el final del seguimiento (3 años). Se calculó la tasa de incidencia acumulada (cumulative incidence proportion, CIP) de RS a 1 y 3 años utilizando la muerte como factor de riesgo competitivo. Se identificaron los factores predictivos de SR mediante regresión múltiple de Cox. RESULTADOS: De los 6.859 pacientes incluidos, el 35,7%, 41,9% y 22,4% tenían una RRR con DS, una RRR sin estoma y una HO con colostomía terminal, respectivamente. En pacientes con SD, el CIP de SR fue del 70,3% (i.c. del 95%: 68,4-72,1) al año y del 74,3% (i.c. del 95%: 72,5-76,0) a los 3 años. Se identificaron como posibles factores predictivos relacionados con el retraso del SR, el tratamiento neoadyuvante (cociente de riesgos instantáneos, hazard ratio, HR 0,75; i.c. del 95% 0,66-0,85), una pérdida de sangre > 300 mL (HR 0,86; i.c. del 95% 0,76-0,97), la fuga anastomótica (HR 0,41; i.c. del 95% 0,33-0,50), las categorías T3 (HR 0,63; i.c. del 95% 0,47-0,83) y T4 (HR 0,62; i.c. del 95% 0,42-0,90) y el estadio IV UICC (HR 0,57; i.c. del 95%: 0,41-0,80). CONCLUSIÓN: En una cuarta parte de los pacientes no se había cerrado el estoma derivativo tres años después de la resección de cáncer rectal con intención reconstructiva.

Overall risk and risk factors for metachronous peritoneal metastasis after colorectal cancer surgery: a nationwide cohort study.

BACKGROUND: This study aimed to identify the cumulative incidence and risk factors of metachronous peritoneal metastasis (M-PM) from colorectal cancer in patients who had intended curative treatment. METHODS: Patients with colorectal cancer were identified using the Danish Colorectal Cancer Group database for 2006-2015. The Danish Pathology Registry and the Danish National Patient Registry were used to identify M-PM to 2017. Risk factors were estimated by multivariable absolute risk regression, treating death and other cancers as competing risks. Overall risk and risk differences (RDs) were estimated at 1, 3 and 5 years. RESULTS: In 22 586 patients with colorectal cancer, the overall risk of M-PM was reported to be 0·9 (95 per cent c.i. 0·8 to 1·0) per cent at 1 year, 1·9 (1·8 to 2·1) per cent at 3 years and 2·2 (2·0 to 2·4) per cent at 5 years. Advanced tumour category ((y)pT4 versus (y)pT1) increased the RD of both M-PM (2·9 (95 per cent c.i. 2·1 to 3·7) at 1 year and 6·0 (4·9 to 7·2) at 3 years) and lymph node involvement ((y)pN2 versus (y)pN0) (2·5 (1·8 to 3·2) at year and 4·3 (3·2 to 5·3) at 3 years). No further increase in risk was observed at 5 years. In a subanalysis, tumour-involved resection margin (R1 versus R0) was associated with M-PM with a RD of 3·9 (1·6 to 6·2) at 1 year and 5·9 (2·6 to 9·3) at 3 years. CONCLUSION: The overall risk of M-PM in patients with colorectal cancer is low, but is increased in advanced T and N status. Follow-up of at least 3 years after colorectal cancer surgery may be necessary, given the potential curative treatment of early diagnosed M-PM.

ANTECEDENTES: Este estudio tuvo como objetivo identificar la incidencia acumulada y los factores de riesgo de metástasis peritoneales metacrónicas (metachronous peritoneal metastases, M-PM) del cáncer colorrectal en pacientes que se sometieron al tratamiento curativo previsto. MÉTODOS: Se identificaron los pacientes con cáncer colorrectal a partir de la base de datos del grupo danés de cáncer colorrectal (Danish Colorectal Cancer Group) durante el periodo 2006-2015. El Registro Danés de Patología (Danish Pathology Registry) y el Registro Nacional Danés de Pacientes (Danish National Patient Registry) se utilizaron para identificar los casos de M-PM hasta el 2017. Los factores de riesgo se estimaron mediante una regresión de riesgo absoluto multivariable, tratando la muerte y otros tipos de cáncer como riesgos competitivos. El riesgo general y las diferencias de riesgo (risk differences, RD) se estimaron a 1, 3 y 5 años. RESULTADOS: De los 22.586 pacientes con CCR, el riesgo global de M-PM fue del 0,9% (i.c. del 95%: 0,8 a 1,0) al año, 1,9 (i.c. del 95%: 1,8 a 2,1) a los 3 años y 2,2 (i.c. del 95%: 2,0 a 2.4) después de 5 años. El estadio T tumoral avanzado ((y) pT4 versus (y) pT1) aumentó el riesgo de M-PM, DR a 1 año: 2,9% (i.c. del 95%: 2,1 a 3,), 3 años: 6,0 (i.c. 95% 4,9 a 7,2), así como la afectación de los ganglios linfáticos ((y) pN2 versus (y) pN0), 1 año: 2,5 (i.c. 95% 1,8 a 3,2), 3 años: 4,3 (i.c. 95% 3,2 a 5,3). No se observó un aumento adicional en la DR después de 5 años. Los márgenes de resección tumoral (R1 versus R0) se asociaron con una DR a 1 año de 3,9 (i.c. del 95% 1,6 a 6,2), y a 3 años de 5,9 (i.c. del 95% 2,6 a 9,3) de riesgo de M-PM en un subanálisis. CONCLUSIÓN: El riesgo global de M-PM en el cáncer colorrectal en pacientes es bajo, pero aumenta en las categorías de estadios T y N avanzados. Puede ser necesario un seguimiento de al menos 3 años después de la cirugía de CCR, dado el tratamiento potencialmente curativo de la M-PM diagnosticada precozmente.

Nationwide cohort study of the impact of education, income and social isolation on survival after acute colorectal cancer surgery.

BACKGROUND: Acute colorectal cancer surgery has been associated with a high postoperative mortality. The primary aim of this study was to examine the association between socioeconomic position and the likelihood of undergoing acute versus elective colorectal cancer surgery. A secondary aim was to determine 1-year survival among patients treated with acute surgery. METHODS: All patients who had undergone a surgical procedure according to the Danish Colorectal Cancer Group (DCCG.dk) database, or who were registered with stent or diverting stoma in the National Patient Register from 2007 to 2015, were reviewed. Socioeconomic position was determined by highest attained educational level, income, urbanicity and cohabitation status, obtained from administrative registries. Co-variables included age, sex, year of surgery, Charlson Co-morbidity Index score, smoking status, alcohol consumption, BMI, stage and tumour localization. Logistic regression analysis was performed to determine the likelihood of acute colorectal cancer surgery, and Kaplan-Meier and Cox proportional hazards regression methods were used for analysis of 1-year overall survival. RESULTS: In total, 35 661 patients were included; 5310 (14·9 per cent) had acute surgery. Short and medium education in patients younger than 65 years (odds ratio (OR) 1·58, 95 per cent c.i. 1·32 to 1·91, and OR 1·34, 1·15 to 1·55 respectively), low income (OR 1·12, 1·01 to 1·24) and living alone (OR 1·35, 1·26 to 1·46) were associated with acute surgery. Overall, 40·7 per cent of patients died within 1 year of surgery. Short education (hazard ratio (HR) 1·18, 95 per cent c.i. 1·03 to 1·36), low income (HR 1·16, 1·01 to 1·34) and living alone (HR 1·25, 1·13 to 1·38) were associated with reduced 1-year survival after acute surgery. CONCLUSION: Low socioeconomic position was associated with an increased likelihood of undergoing acute colorectal cancer surgery, and with reduced 1-year overall survival after acute surgery.

ANTECEDENTES: La cirugía urgente del cáncer colorrectal se ha asociado con una mortalidad postoperatoria elevada. El objetivo principal de este estudio fue determinar la relación entre el estatus socioeconómico y la probabilidad de indicación de cirugía de cáncer colorrectal de forma urgente o electiva. El objetivo secundario fue determinar la supervivencia a 1 año en los pacientes tratados con cirugía urgente. MÉTODOS: Se revisaron todos los pacientes en los que se había realizado un procedimiento quirúrgico recogidos en la base de datos Danish Colorectal Cancer (DCCG.dk) o que se hubiera colocado una prótesis o efectuado un estoma de derivación que constasen en el National Patient Register entre 2007 y 2015. El estatus socioeconómico se estableció según el nivel más alto de educación alcanzado, los ingresos, el lugar de residencia y la situación de convivencia, datos que se obtuvieron de registros administrativos. Las covariables analizadas fueron el género, la edad, el año de la cirugía, el índice de comorbilidad de Charlson, el hábito tabáquico, el consumo de alcohol, el índice de masa corporal, el estadio y la localización del tumor. Se calcularon las regresiones logísticas según la probabilidad de cirugía de cáncer colorrectal urgente y se utilizó el método de Kaplan Meier y Cox para el análisis de la supervivencia global a 1 año. RESULTADOS: Se incluyeron 35.661 pacientes, de los que a 5.310 (15%) se realizó un procedimiento quirúrgico de urgencia. Los factores que se asociaron a cirugía urgente fueron un nivel educativo bajo o medio en menores de 65 años (razón de oportunidades, odds ratio, OR = 1,58, i.c del 95% 1,32-1,91 y OR = 1,34, i.c. del 95% 1,15-1,55, respectivamente), los bajos ingresos (OR = 1,12, i.c del 95% 1,01 -1,24) y vivir solo (OR = 1,35, i.c. del 95% 1,26-1,46). El 41,0% de los pacientes a los que se realizó cirugía urgente fallecieron en el primer año postoperatorio. Los factores asociados con una baja tasa de supervivencia al año de la cirugía urgente fueron un nivel educativo bajo (cociente de riesgos instantáneos, hazard ratio, HR = 1,18, i.c. del 95% 1,03-1,36), unos ingresos bajos (HR = 1,16, i.c. del 95% 1,01-1,34) y vivir solo (HR = 1,25, i.c. del 95% 1,13-1,38). CONCLUSIÓN: La probabilidad de ser sometido a cirugía urgente por un cáncer colorrectal y ver reducida la probabilidad de supervivencia en el primer año postoperatorio es mayor en pacientes con un estatus socioeconómico bajo.

Therapeutic delay reduces survival of rectal cancer but not of colonic cancer.

BACKGROUND: The relationship between therapeutic delay and long-term survival from colorectal cancer is unclear. This association was examined prospectively among patients with colorectal cancer in Denmark. METHODS: A total of 740 patients with colorectal cancer were included in a prospective, population-based study in three Danish counties from 1 January 2001 to 31 July 2002. Delay was determined by self-report during a standardized interview. Cox proportional hazards regression was used to compute the hazard ratio (HR) associated with delay, while adjusting for age, sex and co-morbidity, and also for urgency of surgery in patients with colonic cancer. RESULTS: For rectal cancer only, a time span of at least 60 days from the onset of symptoms until treatment (total therapeutic delay) was associated with a 69 per cent higher risk of mortality compared with a total therapeutic delay of less than 60 days (HR 1.69 (95 per cent confidence interval 1.01 to 2.83)). Provider delay (interval from first physician contact until treatment) and hospital delay (interval from referral to a hospital until treatment) of at least 60 days had no impact on survival from colorectal cancer. CONCLUSION: A total therapeutic delay of at least 60 days was a negative prognostic factor for long-term survival from rectal cancer.

Time trends of short-term mortality for octogenarians undergoing a colorectal resection in North Europe.

BACKGROUND: Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims to gain an overview and time trends of short-term mortality in octogenarians (≥80 years) with colorectal cancer across four North European countries. METHODS: Patients of 80 years or older, operated for colorectal cancer (stage I-III) between 2005 and 2014, were included. Population-based cohorts from Belgium, Denmark, the Netherlands, and Sweden were collected. Separately for colon- and rectal cancer, 30-day, 90-day, one-year, and excess one-year mortality were calculated. Also, short-term mortality over three time periods (2005-2008, 2009-2011, 2012-2014) was analyzed. RESULTS: In total, 35,158 colon cancer patients and 10,144 rectal cancer patients were included. For colon cancer, 90-day mortality rate was highest in Denmark (15%) and lowest in Sweden (8%). For rectal cancer, 90-day mortality rate was highest in Belgium (11%) and lowest in Sweden (7%). One-year excess mortality rate of colon cancer patients decreased from 2005 to 2008 to 2012-2014 for all countries (Belgium: 17%-11%, Denmark: 21%-15%, the Netherlands: 18%-10%, and Sweden: 10%-8%). For rectal cancer, from 2005 to 2008 to 2012-2014 one-year excess mortality rate decreased in the Netherlands from 16% to 7% and Sweden: 8%-2%). CONCLUSIONS: Short-term mortality rates were high in octogenarians operated for colorectal cancer. Short-term mortality rates differ across four North European countries, but decreased over time for both colon and rectal cancer patients in all countries.

Postoperative medical complications are the main cause of early death after emergency surgery for colonic cancer.

BACKGROUND: Only a few small studies have evaluated risk factors related to early death following emergency surgery for colonic cancer. The aim of this study was to identify risk factors for death within 30 days after such surgery. METHODS: Some 2157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 were identified from the national colorectal cancer registry. Thirty-day mortality rates were calculated and risk factors for early death were identified using logistic regression analysis. RESULTS: The overall 30-day mortality rate was 22.1 per cent. The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 per cent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other independent risk factors were age at least 71 years, male sex, American Society of Anesthesiologists grade III or more, palliative outcome, tumour perforation, splenectomy and adverse intraoperative surgical events. Postoperative surgical complications were noted in 20.4 per cent of the patients but had no statistically significant influence on mortality. CONCLUSION: Emergency surgery for colonic cancer is still associated with an increased risk of death. There is a need for a system providing increased safety in the perioperative period.