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Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3-12.1) vs. 12.5 months (95% CI: 11.2-13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2-46.8) vs. 40.8 months (95% CI: 28.8-46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS.
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Importance: Management of colorectal cancer (CRC) has been updated continuously over the past 2 decades. While the combination of these initiatives has had implications for improved survival, the implications for rates of recurrence remain unexplored. Objective: To ascertain the rates of recurrence and describe time to recurrence within 5 years of surgery with curative intent for stages I to III CRC. Design, Setting, and Participants: This cohort study used the Danish Colorectal Cancer Group Database to identify patients with Union for International Cancer Control (UICC) stages I to III CRC who underwent primary surgery between January 1, 2004, and December 31, 2019. They were followed up until recurrence (event), death (competing event), diagnosis of a second cancer (competing event), emigration (censoring event), 5 years postoperatively (censoring event), or January 1, 2023 (censoring event), whichever came first. Recurrence status was ascertained through individual-level linked data from the Danish Cancer Registry, Danish National Patient Registry, and Danish Pathology Registry using a validated algorithm. Data were analyzed from January 1 to August 8, 2023. Exposure: Primary surgery performed during 3 calendar periods (2004-2008, 2009-2013, and 2014-2019) stratified by tumor site (colon or rectum) and UICC stage (I, II, and III). Main Outcomes and Measures: Stage-specific 5-year recurrence reported as the cumulative incidence function (CIF) of recurrence, the association between calendar period of primary surgery and recurrence risk reported as subdistribution hazard ratios (sHRs), and the time from surgery to recurrence. Results: Of the 34â¯166 patients with UICC stages I to III CRC (median [IQR] age, 70 [62-77] years); 18 552 males [54.3%]) included in the study, 7027 developed recurrence within 5 years after the primary surgery. For colon cancer, the 5-year CIF of recurrence decreased over the 3 calendar periods from 16.3% to 6.8% for UICC stage I, from 21.9% to 11.6% for UICC stage II, and from 35.3% to 24.6% for UICC stage III colon cancer. For rectal cancer, the 5-year CIF decreased over the 3 periods from 19.9% to 9.5% for stage I, from 25.8% to 18.4% for stage II, and from 38.7% to 28.8% for stage III disease. Patients with stage III disease had a shorter time from surgery to recurrence compared with those with stage I disease (time ratio stage III vs stage I = 0.30; 95% CI, 0.28-0.32). Cancers detected through screening were associated with lower stage-adjusted risks of recurrence (sHR, 0.81; 95% CI, 0.73-0.91) compared with cancers not detected through screening. Conclusions and Relevance: In this cohort of patients with CRC, the risk of recurrence decreased in patients with stages I to III disease during the study period. Cancer detection by screening was associated with an even lower risk of recurrence. Time to recurrence differed according to UICC stage. Because the risk of recurrence was so low in selected patient groups, future research is warranted to explore risk-stratified surveillance protocols in patients with CRC.
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Neoplasias do Colo , Neoplasias Colorretais , Masculino , Humanos , Idoso , Estudos de Coortes , Incidência , Assistência ao Convalescente , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/diagnóstico , Neoplasias do Colo/patologia , Dinamarca/epidemiologiaAssuntos
Neoplasias do Apêndice , Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias do Apêndice/patologia , Neoplasias Peritoneais/terapia , Qualidade de Vida , Peritônio/patologia , Progressão da Doença , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de CitorreduçãoRESUMO
BACKGROUND: Colorectal cancer with peritoneal metastases can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Treatment may result in biopsychosocial late effects (LEs). We explored the frequency and severity of the following biopsychosocial LEs: anxiety, depression, fear of cancer recurrence (FCR), insomnia, fatigue, cognitive impairment, and pain, and evaluated their impact on quality of life (QoL). METHOD: This was a national prospective cohort study screening for LEs during the period January 2021-May 2023. Patients completed the following questionnaires: General Anxiety Disorder-7, Patient Health Questionnaire-9, FCR Inventory-Short Form, Insomnia Severity Index, Functional Assessment of Chronic Illness Therapy-Fatigue, cognitive impairment (six items from the European Organisation for Research and Treatment of Cancer Item Library), and the Rectal Cancer Pain Score. Preregistration was completed at ClinicalTrials.gov (NCT04956107). RESULT: In total, 99 patients were included. The mean age was 61 years and 57% were women. At 3 months after surgery, the frequent LEs were fatigue (72%), FCR (58%), and pain (48%), and at 12 months after surgery, the frequent LEs were FCR (65%), fatigue (40%), and insomnia (33%). More than half of the patients (54%) reported at least two LEs after 12 months. Patients with moderate-to-severe LEs reported a lower QoL than patients with no/mild LEs. Patients with no/mild LEs had a similar QoL as the Danish norm population. CONCLUSION: Biopsychosocial LEs were prevalent. The QoL of patients reporting LEs in the worst severity categories was negatively impacted. Screening and treatment for these LEs should be a focus in cancer survivor follow-up.
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Neoplasias do Apêndice , Neoplasias Colorretais , Terapia Combinada , Neoplasias Peritoneais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Ansiedade/epidemiologia , Neoplasias do Apêndice/terapia , Neoplasias Colorretais/terapia , Terapia Combinada/efeitos adversos , Procedimentos Cirúrgicos de Citorredução , Fadiga , Quimioterapia Intraperitoneal Hipertérmica , Dor/epidemiologia , Neoplasias Peritoneais/terapia , Estudos Prospectivos , Qualidade de Vida , Distúrbios do Início e da Manutenção do Sono/epidemiologia , IdosoRESUMO
AIM: To investigate the impact of the surgical extent on late adverse effects (LAE) following cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHOD: A prospective cohort study including patients undergoing CRS + HIPEC due to peritoneal metastases from gastrointestinal tumour origin. From 2006 through 2019, consecutive patients treated with CRS + HIPEC were followed at 3, 6 and 12 months, and LAEs were assessed using the symptom scales and items from the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30). Surgical extent was categorized into three groups (major, intermediate, minor) based on peritonectomy procedures and colorectal resections performed as part of CRS. EORTC data were analysed using a linear mixed effects regression model adjusted for age, gender, origin of tumour and comorbidity. RESULTS: In total, 257 patients who responded to at least one questionnaire during the follow-ups were included. Only diarrhoea symptoms were positively associated with surgical extent (mean differences: major vs. minor: 8.4 (-0.5; 17.2) (p = 0.06) and major vs. intermediate: 10.9 (3.8; 18.0) (p = 0.00)). Additionally, diarrhoea symptoms persisted throughout the study period and did not change over time (mean difference 12-3 months: -3.6 (-9.1; 1.7) (p-value = 0.18)). Overall, the levels of different symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, and appetite loss) significantly decreased from 3 to 12 months. CONCLUSION: Patients undergoing extensive CRS suffer from persistent impaired gastrointestinal function in terms of diarrhoea compared patients undergoing to less extensive surgery. Attention should be directed at detecting such LAE and to guide patients accordingly.
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Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Estudos Prospectivos , Neoplasias Peritoneais/secundário , Quimioterapia do Câncer por Perfusão Regional/métodos , Hipertermia Induzida/efeitos adversos , Diarreia/tratamento farmacológico , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de SobrevidaRESUMO
Objectives: Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2â¯% of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice. Methods: This was a retrospective national cohort study. All patients were treated at Aarhus University Hospital; the only CRS+HIPEC centre in Denmark. We included CRC patients managed with curative intent for simultaneously diagnosed PM and LM in the period January 2016 - December 2021. LM was treated with RFA as first choice, if possible. Survival was calculated by the Kaplan-Meier method. Results: A total of 25 patients were included, the median age was 60 years (range 43-75 years) and 15 (60â¯%) were females. The median peritoneal cancer index was 7 (range 0-12), the median number of LM was 1 (range 1-3). Ablation was performed as the only treatment for LM in 18 (72â¯%) patients. After a median follow-up time of 17.1 months (range 4-36 months), the median OS was 28.6 months (95â¯% confidence interval (Cl) 15.8;36.1), 1-year OS was 84.0â¯% (95â¯% Cl 62.8;93.7). Median DFS was 6.1 months (95â¯% Cl 4.0;10.3). Median LOS was ten days (range 5-26 days). Both 30-day and 90-day mortality were 0â¯%. Conclusions: The selected treatment modality (RFA) for CRC patients with both LM and PM was safe. However, DFS was low. Further research is warranted to investigate if RFA is as effective as LM resection.
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PURPOSE: Anastomotic leakage (AL) after colorectal resection is a serious postoperative complication with grave consequences for patients. Despite several efforts to reduce its incidence, AL is still seen among 2-20% of colorectal cancer patients receiving an anastomosis. The use of tissue adhesives and sealants as an extra layer of protection around the anastomosis has shown promising results. We conducted a scoping review to provide an overview of the current knowledge on the effect of tissue adhesives and sealants on colorectal anastomosis healing, as well as their effect on the postoperative outcome. METHODS: The databases of PubMed, Embase, and Cochrane Library were systematically searched on 14/10/2022. Studies addressing the use of a tissue adhesive or tissue sealant applied around a colorectal anastomosis, with the goal to prevent AL or to decrease AL-related complications, were included. We presented an overview of the available studies and summarized their results narratively. RESULTS: Seven studies were included out of the 846 screened. All authors reported the rate of AL in their interventions group. Five of the studies found a decreased rate of AL compared to the control group. One study had no incidences of AL, while the last study had a seemingly low rate of AL but no comparison group. Information on secondary outcomes was sparingly reported, but the results hinted at a positive effect. CONCLUSION: Tissue adhesives and sealants might have a beneficial effect on colorectal anastomosis healing. The literature is sparse, and this review has shown the need for further clinical studies.
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Neoplasias Colorretais , Adesivos Teciduais , Humanos , Adesivos Teciduais/farmacologia , Adesivos Teciduais/uso terapêutico , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Cicatrização , Neoplasias Colorretais/cirurgiaRESUMO
AIM: The complete mesocolic excision competency assessment tool (CMECAT) is a novel tool designed to assess technical skills in minimally invasive complete mesocolic excision (CME) surgery. The aim of this study was to assess construct validity and reliability of CMECAT in a clinical context. METHOD: Colorectal surgeons were asked to submit video recorded laparoscopic CME resections for independent assessment of their technical abilities. The videos were grouped by surgeons' training level, and four established CME experts were recruited as CMECAT assessors. Extended reliability analysis (G-theory) was applied to describe assessor agreement. RESULTS: A total of 19 videos and 72 assessments were included in the analysis. Overall, technical skills assessed by CMECAT improved with increased training level: the experts scored significantly better than the untrained surgeons (3.3 vs. 2.5 points; p < 0.01). On right-sided resections, significantly higher scores were reported with increased training level for all categories and sections, while for left-sided resections, the variance across groups was smaller and significantly higher scores were only reported for oncological safety describing items. Overall, assessor agreement was high (G-coefficient: 0.81). CONCLUSION: This study confirms that CMECAT can be applied to video recorded CME cases for technical skill assessment. Further, it can reliably assess technical performance in right sided CME surgery, where construct validity has now been established. More videos are required to evaluate its validity on left colonic CME. In the future, we hope CMECAT can improve feedback during CME training, serve as a tool in certification processes and contribute to distinguishing CME from conventional surgery in future research.
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Neoplasias do Colo , Laparoscopia , Mesocolo , Humanos , Excisão de Linfonodo , Neoplasias do Colo/cirurgia , Reprodutibilidade dos Testes , Mesocolo/cirurgia , Colectomia , Resultado do TratamentoRESUMO
PURPOSE: The literature reports a varying occurrence (3-33%) of blowout of the rectal remnant after Hartmann's procedure, and there is a lack of multivariate analyses on potential risk factors for blowout following Hartmann's procedure. We aimed to estimate the incidence of blowout within 90 days after a primary Hartmann's procedure and to identify potential risk factors for blowout through multivariate analysis. METHODS: A retrospective cohort study was conducted at the Department of Surgery, Aarhus University Hospital, a Danish primary and tertiary hospital. Patients who underwent primary surgery with Hartmann's procedure irrespective of surgical setting and indications between September 2016 and August 2021 were included. Blowout was defined as a defective closure line of the rectal stump or a pelvic abscess. RESULTS: A total of 178 patients were included, and blowout occurred in 30 patients (16.9%) within 90 days after a primary Hartmann's procedure. Multivariate analysis showed increased risk of blowout among patients with Hinchey IV diverticulitis (relative risk 6.32 (95% CI 4.09-9.75)), previous radiotherapy (relative risk 3.35 (95% CI 1.67-6.74)), and alcohol overconsumption (relative risk 1.69 (95% CI 1.05-2.72)). Intraoperative insertion of a Foley catheter in the rectal remnant significantly reduced the risk of blowout within 90 days after a primary Hartmann's procedure (relative risk 0.18 (95% CI 0.05-0.65)). CONCLUSION: Blowout remains a severe and common complication within 90 days after a primary Hartmann's procedure. Hinchey IV diverticulitis, pelvic radiotherapy, and alcohol overconsumption are risk factors. An intraoperatively inserted rectal Foley catheter is a protective factor and can be considered used in all patients undergoing Hartmann's procedure.
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Diverticulite , Reto , Humanos , Incidência , Estudos Retrospectivos , Reto/cirurgia , Diverticulite/complicações , Colostomia/efeitos adversos , Fatores de Risco , Anastomose Cirúrgica/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
PURPOSE: After curatively intended rectal cancer (RC) surgery, new follow-up strategies are warranted, seeking more individualised care and targeting health-related quality of life (HRQoL) and functional outcomes. The FURCA trial aimed to investigate the effect of patient-led follow-up on HRQoL and symptom burden 3 years after surgery. METHODS: RC patients from four Danish centres were randomised 1:1 to intervention (patient-led follow-up with patient education and self-referral to a specialist nurse) or control (standard follow-up with five routine doctor visits). Patients in both groups had a computed tomography (CT) at 1 and 3 years. The primary outcome (HRQoL) was assessed by the Functional Assessment of Cancer Therapy - colorectal (FACT-C) score (Ward et al. in Qual Life Res. 8(3):181-95, 18). Secondary outcomes were functional measures, patient involvement and satisfaction and cancer recurrence at 3 years. RESULTS: From Feb 2016 to Aug 2018, 336 patients were included of whom 248 completed 3 years of follow-up. Between-group differences were found neither for the primary endpoint, nor for functional outcomes. The recurrence rate did not differ between the groups. Patient involvement and satisfaction were higher in the intervention group with statistical significance in almost half of the items. CONCLUSIONS: We found no effect on HRQoL and symptom burden from patient-led follow-up, although it may improve patient-perceived involvement and satisfaction. IMPLICATIONS FOR CANCER SURVIVORS: The findings in this study suggest that patient-led follow-up is a more tailored approach to meet cancer survivors' needs and might improve their ability to cope with survivorship. GOV IDENTIFIER: R97-A6511-14-S23.
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PURPOSE: Anastomotic leakage after colorectal cancer resection is a feared postoperative complication seen among up till 10-20% of patients, with a higher risk following rectal resection than colon resection. Recent studies suggest that the combined use of preoperative mechanical bowel preparation and oral antibiotics may have a preventive effect on anastomotic leakage. This systematic review aims to explore the association between preoperative mechanical bowel preparation combined with oral antibiotics and the risk of anastomotic leakage following restorative resection for primary rectal cancer. METHODS: Three databases were systematically searched in February 2022. Studies reporting anastomotic leakage rate in patients, who received mechanical bowel preparation and oral antibiotics before elective restorative resection for primary rectal cancer, were included. A meta-analysis was conducted based on the risk ratios of anastomotic leakage. RESULTS: Among 839 studies, 5 studies met the eligibility criteria. The median number of patients were 6111 (80-29,739). The combination of preoperative mechanical bowel preparation and oral antibiotics was associated with a decreased risk of anastomotic leakage (risk ratio = 0.52 (95% confidence interval 0.39-0.69), p-value < 0.001). Limitations included a low number of studies, small sample sizes and the studies being rather heterogenous. CONCLUSION: This systematic review and meta-analysis found that the use of mechanical bowel preparation and oral antibiotics is associated with a decreased risk of anastomotic leakage among patients undergoing restorative resection for primary rectal cancer. The limitations of the review should be taken into consideration when interpreting the results.
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Antibacterianos , Neoplasias Retais , Humanos , Antibacterianos/uso terapêutico , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Fístula Anastomótica/tratamento farmacológico , Infecção da Ferida Cirúrgica/etiologia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Cuidados Pré-Operatórios/métodos , Neoplasias Retais/tratamento farmacológicoRESUMO
OBJECTIVE: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients. METHODS: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients. RESULTS: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12-2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22-5.03) and Stage II (OR = 1.76, 95%CI: 1.11-2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44-1.53) patients. CONCLUSION: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.
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AIM: To (1) develop an assessment tool for laparoscopic complete mesocolic excision (LCME) and (2) report evidence of its content validity. METHOD: Assessment statements were revealed through (1) semi-structured expert interviews and (2) consensus by the Delphi method, both involving an expert panel of five LCME surgeons. All experts were interviewed and then asked to rate LCME describing statements from 1 (strongly disagree) to 5 (strongly agree). Responses were returned anonymously to the panel until consensus was reached. Statements were directly included as content in the assessment tool if ≥60% of the experts responded "agree" or "strongly agree" (ratings 4 and 5), with the remaining responses being "neither agree nor disagree" (rating 3). Interclass correlation coefficient (ICC) was calculated for expert agreement evaluation. All included statements were subsequently reformulated as tool items and approved by the experts. RESULTS: Four Delphi rounds were performed to reach consensus. Disagreement was reported for statements describing instrument handling around pancreas; visualisation of landmarks before inferior mesenteric artery ligation; lymphadenectomy around the inferior mesenteric artery, and division of the terminal ileum and transverse colon. ICC in the last Delphi-round was 0.84. The final tool content included 73 statements, converted to 48 right- and 40 left-sided items for LCME assessment. CONCLUSION: A procedure-specific, video-based tool, named complete mesocolic excision competency assessment tool (CMECAT), has been developed for LCME skill assessment. In the future, we hope it can facilitate assessment of LCME surgeons, resulting in improved patient outcome after colon cancer surgery.
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Colo Transverso , Neoplasias do Colo , Laparoscopia , Humanos , Laparoscopia/métodos , Neoplasias do Colo/cirurgia , Colo Transverso/cirurgia , Excisão de Linfonodo/métodos , Ligadura , Técnica DelphiRESUMO
BACKGROUND: Despite increasing focus on the technical performance of total mesorectal excision over recent decades, anastomotic leakage (AL) continues to be a serious complication for many patients, even in the hands of experienced surgical teams. This study describes implementation of standardized surgical technique in an effort to reduce variability, decrease the risk of anastomotic leakage, and improve associated short-term outcomes for rectal cancer patients undergoing robot-assisted restorative rectal resection (RRR). METHODS: We evaluated all rectal cancer patients undergoing robot-assisted RRR at Aarhus University Hospital between 2017 and 2020. Six standardized surgical steps directed to improve anastomotic healing were mandatory for all RRR. Additional changes were made during the period with prohibition of systemic dexamethasone and limiting the use of endoscopic stapling devices. RESULTS: The use of the full standardization, including all six surgical steps, increased from 40.3% (95% CI, 0.28-0.54) to 86.2% (95% CI, 0.68-0.95). The incidence of AL decreased from 21.0% (95% CI, 0.12-0.33) to 6.9% (95% CI, 0.01-0.23). Length of hospital stay (LOS) decreased from 6 days (range 2-50) to 5 days (range 2-26). The rate of patients readmitted within 90 days decreased from 21.0% (95% CI, 0.12-0.33), to 6.9% (95% CI, 0.01-0.23). CONCLUSION: The full standardization was effectively implemented for rectal cancer patients undergoing robot-assisted RRR. The risk of AL, LOS and readmission decreased during the study period. A team focus on high-reliability and peri-operative complications can improve patient outcomes.
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Neoplasias Retais , Robótica , Fístula Anastomótica , Estudos de Coortes , Dexametasona , Humanos , Neoplasias Retais/cirurgia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity. Yet, empirical evidence supporting performance gains of MT vs. single-target (ST) strategies in a postoperative setting is limited. We compared ctDNA detection in 379 paired plasma samples from 112 stage II-III colorectal cancer patients by ST digital PCR and MT sequencing of 16 patient-specific variants. The strategies exhibited good concordance (90%, Cohen's Kappa 0.79), with highly correlated ctDNA quantifications (Pearson r = 0.985). A difference was observed in ctDNA detection preoperatively (ST 72/92, MT 88/92). However, no difference was observed immediately after surgery in recurrence (ST 11/22, MT 10/22) or nonrecurrence (both 2/34) patients. In serial samples, detection was similar within recurrence (ST 13/16, MT 14/16) and nonrecurrence (ST 3/49, MT 1/49) patients. Both approaches yielded similar lead times to standard-of-care radiology (ST 4.0 months, MT 4.1 months). Our findings do not support significant performance gains of the MT strategy over the ST strategy for postoperative ctDNA detection.
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DNA Tumoral Circulante , Neoplasias Colorretais , Humanos , DNA Tumoral Circulante/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/diagnósticoRESUMO
PURPOSE: Anastomotic leakage (AL) continues to be a challenge after restorative rectal resection (RRR). Various treatment options of AL are available; however, their long-term outcomes are uncertain. We explored the impact of AL on the risk of stoma presence 1 year after RRR for rectal cancer and described treatment of AL after RRR including impact on the probability of receiving adjuvant chemotherapy and stoma presence following different treatment options of AL. METHODS: We included 859 patients undergoing RRR in Central Denmark Region between 2013 and 2019. Stoma presence was calculated as the proportion of patients with stoma 1 year after RRR. Multivariable logistic regression was conducted to estimate the impact of AL on stoma presence adjusting for potential predictors. Descriptive data of outcomes were stratified for various treatment options of AL. RESULTS: The risk of stoma presence 1 year after surgery was 9.8% (95% CI 7.98-12.0). Predictors for having stoma 1 year after RRR were AL (OR 8.43 (95% CI 4.87-14.59)) and low tumour height (OR 3.85 (95% CI 1.22-13.21)). For patients eligible for adjuvant chemotherapy, the probability of receiving it was 42.9% (95% CI 21.8-66.0) if treated with endo-SPONGE and 71.4% (95% CI 47.8-88.7) if treated with other anastomosis preserving treatment options. The risk of having stoma 1 year after RRR was 33.9% (95% CI 21.8-47.8) for patients treated with endo-SPONGE and 13.5% (95% CI 5.6-25.8) for patients treated with other anastomosis preserving treatment options (p = 0.013). CONCLUSION: AL is a strong predictor for stoma presence 1 year after RRR. Patients treated with endo-SPONGE seem to have worse outcomes compared to other anastomosis preserving treatment options.
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Protectomia , Neoplasias Retais , Estomas Cirúrgicos , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/cirurgia , Fístula Anastomótica/terapia , Humanos , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Estomas Cirúrgicos/efeitos adversos , Estomas Cirúrgicos/patologiaRESUMO
INTRODUCTION: Peritoneal metastases (PM) originating from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP) can be treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Certain sites in the peritoneal cavity are prone to contain PM and are, therefore, routinely resected. The aim of this study is to investigate the frequency of disease in CRS specimens routinely resected. Secondly, to investigate if the risk of finding PM in routinely resected specimen is associated with involvement of anatomic related peritoneal areas. MATERIALS AND METHODS: This study investigated 433 patients diagnosed with PMP (n = 119) or PM from CRC (n = 314) and operated with CRS + HIPEC between June 2006 and November 2020 at a national center. Baseline data were prospectively registered. Pathology reports were reviewed for the presence of metastases in the routinely resected umbilicus, ligamentum teres hepatis, ovaries and greater omentum. Tumor extent was estimated using the Dutch region count. RESULTS: PM was found in 14.7% of umbilical resections, in 17.4% of the resected ligamentum teres hepatis, in 48.2% of the resected ovaries and in 49.5% of the greater omentum specimens. We found an association between macroscopic disease involvement of the nearest region and risk of PM found in the related resections. Seven of 31 women with no macroscopically visible disease in the pelvis had PM diagnosed in the resected ovaries. CONCLUSIONS: A substantial proportion of routine resections held histologic verified PM. Our results may advocate for a routinely performed resection of the umbilicus, ligamentum teres hepatis, ovaries and greater omentum.
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Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Neoplasias Colorretais/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/secundário , Peritônio/patologia , Peritônio/cirurgia , Pseudomixoma Peritoneal/complicações , Pseudomixoma Peritoneal/terapiaRESUMO
BACKGROUND: In laparoscopic colorectal surgery, higher technical skills have been associated with improved patient outcome. With the growing interest in laparoscopic techniques, pressure on surgeons and certifying bodies is mounting to ensure that operative procedures are performed safely and efficiently. The aim of the present review was to comprehensively identify tools for skill assessment in laparoscopic colon surgery and to assess their validity as reported in the literature. METHODS: A systematic search was conducted in EMBASE and PubMed/MEDLINE in May 2021 to identify studies examining technical skills assessment tools in laparoscopic colon surgery. Available information on validity evidence (content, response process, internal structure, relation to other variables, and consequences) was evaluated for all included tools. RESULTS: Fourteen assessment tools were identified, of which most were procedure-specific and video-based. Most tools reported moderate validity evidence. Commonly not reported were rater training, assessment correlation with variables other than training level, and validity reproducibility and reliability in external educational settings. CONCLUSION: The results of this review show that several tools are available for evaluation of laparoscopic colon cancer surgery, but few authors present substantial validity for tool development and use. As we move towards the implementation of new techniques in laparoscopic colon surgery, it is imperative to establish validity before surgical skill assessment tools can be applied to new procedures and settings. Therefore, future studies ought to examine different aspects of tool validity, especially correlation with other variables, such as patient morbidity and pathological reports, which impact patient survival.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Competência Clínica , Colo/cirurgia , Humanos , Laparoscopia/métodos , Reprodutibilidade dos TestesRESUMO
PURPOSE: Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates. EXPERIMENTAL DESIGN: We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples (n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing. RESULTS: Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7-13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4-167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9-172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1-6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography. CONCLUSIONS: Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making.See related commentary by Morris and George, p. 438.