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BACKGROUND: Colon cancer (CC) is a public health concern with increasing incidence in younger populations. Treatment for locally advanced CC (LACC) involves oncological surgery and adjuvant chemotherapy (AC) to reduce recurrence and improve overall survival (OS). Neoadjuvant chemotherapy (NAC) is a novel approach for the treatment of LACC, and research is underway to explore its potential benefit in terms of survival. This trial will assess the efficacy of NAC in LACC. METHODS: This is a multicentre randomised, parallel-group, open label controlled clinical trial. Participants will be selected based on homogenous inclusion criteria and randomly assigned to two treatment groups: NAC, surgery, and AC or surgery followed by AC. The primary aim of this study is to evaluate the 2-year progression-free survival (PFS), with secondary outcomes including 5-year PFS, 2- and 5-year OS, toxicity, radiological and pathological response, morbidity, and mortality. DISCUSSION: The results of this study will determine whether NAC induces a clinical and histological tumour response in patients with CCLA and if this treatment sequence improves survival without increasing morbidity and mortality. REGISTRATION NUMBER: NCT04188158.
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Neoplasias do Colo , Terapia Neoadjuvante , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/terapia , Neoplasias do Colo/cirurgia , Terapia Neoadjuvante/métodos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estudos Multicêntricos como AssuntoRESUMO
AIM: Minimally invasive surgery has been increasingly adopted for locally advanced colon cancer. However, evidence comparing robotic (RRC) versus laparoscopic right colectomy (LRC) for nonmetastatic pT4 cancers is lacking. METHODS: This was a multicentre propensity score-matched (PSM) study of a cohort of consecutive patients with pT4 right colon cancer treated with RRC or LRC. The two surgical approaches were compared in terms of R0, number of lymph nodes harvested, intra- and postoperative complication rates, overall (OS), and disease-free survival (DFS). RESULTS: Among a total of 200 patients, 39 RRC were compared with 78 PS-matched LRC patients. The R0 rate was similar between RRC and LRC (92.3% vs. 96.2%, respectively; p = 0.399), as was the odds of retrieving 12 or more lymph nodes (97.4% vs. 96.2%; p = 1). No significant difference was noted for the mean operating time (192.9 min vs. 198.3 min; p = 0.750). However, RRC was associated with fewer conversions to laparotomy (5.1% vs. 20.5%; p = 0.032), less blood loss (36.9 vs. 95.2 mL; p < 0.0001), fewer postoperative complications (17.9% vs. 41%; p = 0.013), a shorter time to flatus (2 vs. 2.8 days; p = 0.009), and a shorter hospital stay (6.4 vs. 9.5 days; p < 0.0001) compared with LRC. These results were confirmed even when converted procedures were excluded from the analysis. The 1-, 3- and 5-year OS (p = 0.757) and DFS (p = 0.321) did not significantly differ between RRC and LRC. CONCLUSION: Adequate oncological outcomes are observed for RRC and LRC performed for pT4 right colon cancer. However, RRC is associated with lower conversion rates and improved short-term postoperative outcomes.
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PURPOSE: Although not considered standard therapy, neoadjuvant chemotherapy (NAC) is an encouraging alternative for selected patients with locally advanced colon cancer (LAC). The aim of this study was to compare 30-day postoperative outcomes between patients undergoing upfront surgery and those undergoing NAC for LAC. METHODS: Using the ACS-NSQIP data from 2016 to 2020, 11,498 patients with LAC were divided into those who underwent upfront colectomy (96.2%) and those who received NAC (3.8%). The primary outcome was a composite outcome encompassing 30-day major postoperative complications. Propensity score matched (PSM) analysis and multivariable logistic regression were performed. RESULTS: After PSM analysis, there was no statistically significant difference in the development of a major complication. NAC was not significantly associated with the primary outcome. Risk factors for postoperative complications were T4 stage, older age, male sex, black race, smoking, dependent status, severe COPD, hypoalbuminemia, and preoperative transfusion. Laparoscopic and robotic surgery was protective. CONCLUSION: NAC did not increase the odds of developing a major complication.
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Neoplasias do Colo , Laparoscopia , Humanos , Masculino , Terapia Neoadjuvante/efeitos adversos , Colectomia/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
INTRODUCTION: Surgeons may choose an open approach to locally advanced colon cancer (LACC) because of the elevated conversion rate (minimally invasive to open) in these patients (resulting in part from a judgment of the technical feasibility of a minimally invasive approach). Poorer outcomes have been suggested in those requiring conversion from a minimal access to an open approach; however, the influence of conversion has not been studied in LACC. We sought to compare perioperative outcomes in patients with T4aN2 colon cancer undergoing minimally invasive surgery (MIS), planned open (PO), and converted (CN) procedures to evaluate the influence of conversion in this subgroup. METHODS: A retrospective cohort study was conducted using the NSQIP database. Patients with T4aN2 colon cancer undergoing elective resection were included; rectal/unknown tumor location, and T4b disease were excluded (to ensure homogeneity in surgical management). Patients were divided into cohorts based on approach: PO, MIS, and CN. Summary statistics were compared between groups. Multivariable analysis was conducted for mortality and morbidity outcomes. RESULTS: 1286 cases were included (313 PO, 842 MIS, 131 CN); 10.2% underwent conversion. Those undergoing MIS had a shorter length of stay than those undergoing PO or CN (p < 0.0001). On univariable analysis, CN resulted in increased rates of any complication (p < 0.0001). CN also had a greater rate of anastomotic leak (p = 0.0046) and death (p = 0.05). On multivariable analysis, significant predictors of any complication included age, ASA class, M stage, and approach; however, CN did not increase the risk of complication compared with MIS, whereas PO nearly doubled the risk of complication (OR = 1.98, p = 0.0083). The only significant predictor of mortality on multivariable analysis was age (HR = 1.09, p = 0.0002)-approach was not associated with mortality. CONCLUSION: PO confers the greatest risk of suffering any complication. Surgical approach was not associated with death. Results of our study challenge the notion that conversion is associated with the worst perioperative outcomes and an MIS approach should be considered in patients with LACC.
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Neoplasias do Colo , Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
Background and Objectives: Increasing evidence supports the use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC). However, its effectiveness remains controversial. This study explored the safety and efficacy of NAC combined with laparoscopic radical colorectal cancer surgery and adjuvant chemotherapy (AC) for LACC. Materials and Methods: We retrospectively analyzed 444 patients diagnosed with LACC (cT4 or cT3, with ≥5 mm invasion beyond the muscularis propria) in our hospital between 2012 and 2015. Propensity score matching (PSM; 1:2) was performed to compare patients treated with NAC and those treated with adjuvant chemotherapy (AC). Results: Overall, 42 patients treated with NAC were compared with 402 patients who received only AC. After PSM, 42 patients in the NAC group were compared with 84 patients in the control group, with no significant differences in the baseline characteristics between groups. The pathological tumor sizes in the NAC group were significantly smaller than those in the AC group (3.1 ± 2.1 cm vs. 5.8 ± 2.5 cm). Patients in the NAC group had a significantly lower T stage than those in the AC group (p < 0.001). After neoadjuvant chemotherapy, a significant response was observed in four (9.6%) patients, with two (4.8%) showing a complete response. The 5-year overall survival rates (88.1% vs. 77.8%, p = 0.206) and 5-year disease-free survival rates (75.1% vs. 64.2%, p = 0.111) did not differ between the groups. However, the 5-year cumulative rate of distant recurrence was significantly lower in the NAC than in the AC group (9.6% vs. 29.9%, p = 0.022). Conclusions: NAC, combined with AC, could downstage primary tumors of LACC and seems safe and acceptable for patients with LACC, with a similar long-term survival between the two treatments.
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Neoplasias do Colo , Terapia Neoadjuvante , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Estadiamento de Neoplasias , Resultado do Tratamento , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Qualidade de Vida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research. METHODS: PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery. RESULTS: All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre. CONCLUSIONS: Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.
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Neoplasias do Colo , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Fluoruracila , Humanos , Estadiamento de Neoplasias , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos RetrospectivosRESUMO
INTRODUCTION: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC. METHODS: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected. A propensity score matching (PSM; 1:2) was performed and compared patients with clinical tumor (cT) 4 colon cancer who were treated with neoadjuvant CT to patients with cT4 colon cancer treated with adjuvant CT (Fig. 1). RESULTS: A total of 192 patients treated with neoadjuvant CT were compared to 1,954 patients that received adjuvant CT. After PSM, 149 patients in the neoadjuvant group were compared to 298 patients in the control group. No significant differences were found in baseline characteristics after PSM. After neoadjuvant CT, a significant response was observed in 13 (9%) patients with 5 (4%) patients showing a complete response. Complete resection margins (R0) were achieved in 77% in the neoadjuvant group versus 86% in the adjuvant treated group (p = 0.037). Significantly less tumor positive lymph nodes were found in the neoadjuvant group (median 0 vs. 2, p < 0.001). Major complication rates and 5-year overall survival did not differ between both groups (67-65%, p = 0.87). CONCLUSION: Neoadjuvant CT seems safe and feasible with similar long-term survival compared to patients who are treated with adjuvant CT.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Terapia Neoadjuvante , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/efeitos adversos , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Neoplasia Residual , Países Baixos , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT. METHODS: We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS. RESULTS: The median follow-up of patients was 20.5 months (range, 6.1-38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively. CONCLUSION: Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.
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Neoplasias do Colo/radioterapia , Cuidados Intraoperatórios/normas , Recidiva Local de Neoplasia/radioterapia , Radioterapia Adjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Preoperative or neoadjuvant chemotherapy (NAC) has emerged as a novel alternative to treat locally advanced colon cancer (LACC), as in other gastrointestinal malignancies. However, evidence of its efficacy and safety has not yet been gathered in the literature. The aim of the present study was to perform an extensive review of the scientific evidence for NAC in patients with LACC. METHODS: PubMed, EMBASE, MEDLINE and Cochrane Library were searched for a systematic review of the literature from 2010 to 2019. Six eligible studies were included, with a total of 27,937 patients, 1232 of them (4.4%) treated with NAC. There were only one randomized controlled trial, three phase II non-randomized single arm studies and two retrospective studies. RESULTS: The baseline computed tomography scan showed that most of patients had a T3 tumor. The completion rate of the planned neoadjuvant treatment ranged from 52.5 to 93.8%. Between 97.2 and 100% of patients had the scheduled surgery. The median tumor volume reduction after NAC ranged from 62.5 to 63.7%. The anastomotic leak rate in the NAC group ranged from 0 to 7%, with no cases of postoperative mortality. There was major pathological tumor regression in 4-34.7% of cases. Between 84 and 100% of NAC patients had R0-surgery. Survival after NAC seems to be encouraging although significant improvement has only been proven in T4b tumours. CONCLUSIONS: According to our systematic review, the NAC may be a safe and effective emerging therapeutic alternative for treating LACC. This approach, which is still being tested, increases the reliance on accurate radiological staging.
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Neoplasias do Colo , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Humanos , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND: Most race/ethnicity-oriented investigations focus on Caucasian Americans (whites) and African Americans (blacks), leaving Asians, Hispanic white (Hispanics), and other minorities less well studied. Adjuvant chemotherapy (CT) after curative resection is critical to patients with locally advanced colon cancer (LACC). We studied the racial disparities in the adjuvant CT of LACC to aid in selecting optimal treatments for people from different races/ethnicities in this era of precision medicine. METHODS: Patients with American Joint Committee on Cancer (AJCC) stage II or III colon cancer (CC) (together termed as LACC) were included based on Surveillance, Epidemiology, and End Results cancer registry-Medicare linked databases. The log-rank test and Cox multivariate regression analysis were performed to investigate the racial/ethnic disparities in cohorts divided according to the regimen of adjuvant CT. RESULTS: In the LACC patients who did not receive adjuvant CT, Asian patients had better survival than other groups (all, P <0.05). For the fluoropyrimidine cohort, the survival of Asian patients was better than that of whites, blacks, and other minorities (all, P <0.05). For the fluoropyrimidine with oxaliplatin cohort, other minorities had superior survival to other groups (all, P <0.05). Similar findings were demonstrated for patients with AJCC stage II and III CC, and the observed better survival persisted after adjustments in the Cox models. CONCLUSIONS: Among LACC patients not receiving adjuvant CT, Asians achieved better survival than other races/ethnicities. Superior survival was also observed for Asians in the fluoropyrimidine cohort and for other minorities in the fluoropyrimidine with oxaliplatin cohort for AJCC stage III CC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/terapia , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Grupos Raciais/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Colectomia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Medicare/estatística & dados numéricos , Estadiamento de Neoplasias , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Fatores Socioeconômicos , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
AIM: Our aim was to compare short- and long-term oncological outcomes between laparoscopic and open colectomy in T4 colon cancer. METHODS: We retrospectively analysed oncological outcomes of 94 patients who underwent surgery between December 2010 and December 2016 for pT4 colon cancer, with propensity score matching. All patients were treated with curative intent, by either laparoscopic or open en bloc resection. RESULTS: The conversion rate in the laparoscopic group was 17.0%. Blood loss, time to flatus and postoperative hospitalization were significantly less in the laparoscopic group. Postoperative morbidity and mortality within 30 days did not significantly differ between the two groups. R0 resection rates and lymph node harvests were similar between the two groups. At 5 years, laparoscopic outcomes were not inferior to open outcomes (overall survival 56.8% vs 50.2%, P = 0.250; disease-free survival 59.7% vs 41.7%, P = 0.06). CONCLUSION: The laparoscopic approach is safe and feasible for pathologically confirmed T4 colon cancer. It results in a faster postoperative recovery.
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Colectomia/mortalidade , Neoplasias do Colo/cirurgia , Laparoscopia/mortalidade , Idoso , Colectomia/métodos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: In colon cancer, T4 stage is still assumed to be a relative contraindication for laparoscopic surgery considering the oncological safety. The aim of this systematic review with meta-analysis was to evaluate short- and long-term oncological outcomes after laparoscopic surgery for T4 colon cancer, and to compare these with open surgery. METHODS: Using systematic review of literature, studies reporting on radicality of resection, disease-free survival (DFS), and/or overall survival (OS) after laparoscopic surgery for T4 colon cancer were identified, with or without a control group of open surgery. Pooled proportions and risk ratios were calculated using an inverse variance method. RESULTS: Thirteen observational cohort studies published between 2012 and 2017 were included, together consisting of 1217 patients that received laparoscopic surgery and 1357 with an open procedure. The proportion of multivisceral resections was larger in the open group in five studies. Based on 11 studies, the pooled proportion of R0 resection was 0.96 (95% CI: 0.91-0.99) and 0.96 (95% CI: 0.90-0.98) after laparoscopic and open surgery, respectively. Analysing (mainly) T4a subgroups in 6 evaluable studies revealed pooled R0 resection rates of 0.94 in both groups. No significant differences were found between laparoscopic and open surgery for any survival measure: RR 1.07 (95% CI: 0.96-1.20) for 3-year DFS, RR 1.04 (95% CI: 0.95-1.15) for 5-year DFS, RR 1.07 (95% CI: 0.99-1.14) for 3-year OS, and RR 1.05 (95% CI: 0.98-1.12) for 5-year OS. CONCLUSION: Literature on laparoscopic surgery for T4 colon cancer is restricted to non-randomized comparisons with substantial allocation bias. Laparoscopic surgery for T4a tumours might be safe, whereas for T4b colon cancer requiring multivisceral resection it should be applied with caution.
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Colectomia/métodos , Neoplasias do Colo/cirurgia , Laparoscopia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Humanos , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
PURPOSE: The study aimed to compare, using propensity score matching (PSM) analyses, the short- and long-term results of laparoscopic colectomy (LC) versus open colectomy (OC) in a bicentric cohort of patients with T4 colon cancer. METHODS: This is a retrospective PSM analysis of consecutive patients undergoing elective LC or OC for pT4 colon cancer (TNM stage II/III) between 2005 and 2014. RESULTS: Overall, 237 patients were selected. After PSM, 106 LC-and 106 OC-matched patients were compared. LC was associated with longer operative time and lower blood loss than OC (220 vs. 190 min, p < 0.0001; 116 vs. 150 mL, p = 0.002, respectively). LC patients showed a faster recovery, which translated into a shorter hospital stay compared to OC (10.5 vs. 15.3 days, p < 0.0001). Conversion was required in 13 (12.2 %) LC patients. No group difference was observed for 30- and 90-day mortality. R0 resection was achieved in the majority of LC and OC patients (93.9 %). The 1-, 3-, and 5-year overall survival was 99, 76.8, and 58.6 %, respectively, for the LC group and 98, 70.1, and 59.9 %, respectively, for the OC group (p = 0.864). The 1-, 3-, and 5-year disease-free survival was 86.3, 66, 57.6 %, respectively, for the LC group and 79.1, 55.1, and 50.2 % for the OC group (p = 0.261). CONCLUSION: With an acceptable conversion rate, laparoscopy can achieve complete oncologic resections of T4 colon cancer similar to open surgery and can be considered a safe and feasible alternative approach that confers the advantage of a faster recovery.
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Neoplasias do Colo/cirurgia , Laparoscopia , Pontuação de Propensão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Demografia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Pós-Operatórios , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The gold standard treatment for locally advanced colon cancer is curative surgery followed by adjuvant chemotherapy, although this approach is associated with serious concerns, such as high recurrence rates and occasionally unnecessary oversurgery. Neoadjuvant chemotherapy may be a promising strategy for overcoming these issues. This study reports a case of a recurrence-free patient who underwent curative resection without significant organ dysfunction after preoperative chemotherapy for locally advanced sigmoid colon cancer. The tumor coexisted with a large intra-abdominal abscess, and the patient was quite frail at the first visit. We performed percutaneous drainage followed by preoperative panitumumab monotherapy, which yielded favorable outcomes. CASE PRESENTATION: A 78-year-old frail woman was emergently transferred to our hospital with fever and abdominal pain. The diagnosis was locally advanced sigmoid colon cancer stage IIIC (T4bN2aM0) with a large intra-abdominal abscess. Immediate curative surgery was inappropriate, considering both tumor progression and the patient's frailty. We performed percutaneous drainage and colostomy construction, which was followed by seven cycles of preoperative panitumumab monotherapy without significant adverse events. After these treatments, inflammation was well controlled, and the tumor shrank remarkably. Furthermore, the patient recovered well from frailty; therefore, curative sigmoidectomy combined with resection of the left ovary and stoma closure was possible without any postoperative complications. The final pathological finding was T3N0M0, stage IIA disease. The patient was recurrence-free and had no significant organ dysfunction 21 months after the curative surgery. CONCLUSIONS: The management of intra-abdominal abscesses and tailor-made preoperative chemotherapy based on the patient's frailty may have been the key factors responsible for the favorable course of this patient. Although further research is needed on the appropriateness of percutaneous drainage for malignancies related to intra-abdominal abscesses and preoperative panitumumab use for locally advanced colon cancer, the study findings can serve as reference for managing similar cases in an aging society.
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Tumor-infiltrating immune cells, such as lymphocytes and macrophages, have been associated with tumor aggressiveness, prognosis and treatment response in colorectal cancer (CRC). An immune scoring system, Immunoscore (IS), based on tumor-infiltrating T cells in stage I-III CRC, was used to predict prognosis. An alternative immune scoring signature of immune activation (SIA) reflects the balance between anti- and pro-tumoral immune components. The present study aimed to evaluate the prognostic value of modified IS (mIS) and modified SIA (mSIA) in locally advanced pathological T4 (pT4) CRC, including stage IV CRC. Immunohistochemical staining for immune cell markers, such as CD3 (pan-T cell marker), CD8 (anti-tumoral cytotoxic T cell marker) and CD163 (tumor-supportive macrophage marker), in specimens from patients with radically resected pT4 CRC at stages II-IV was performed. mIS levels in the T4 CRC cohort were not associated with prognosis. However, low mSIA levels were associated with low survival. Furthermore, low mSIA was an independent predictor of recurrence in patients with radically resected pT4 CRC. In patients with CRC who did not receive postoperative adjuvant chemotherapy, low mSIA was a major poor prognostic factor; however, this was not observed in patients receiving adjuvant chemotherapy. Evaluation of the tumor-infiltrating immune cell population could serve as a valuable marker of recurrence and poor prognosis in patients with locally advanced CRC. mSIA assessment after radical CRC resection may be promising for identifying high-risk patients with pT4 CRC who require aggressive adjuvant chemotherapy.
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Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.
Assuntos
Neoplasias do Colo , Humanos , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/terapia , Terapia Neoadjuvante , Taxa de SobrevidaRESUMO
BACKGROUND: The treatment of locally advanced colon cancer is challenging, particularly when there is invasion of the abdominal wall. In such cases, balancing the securing of margins and sufficiently repairing abdominal wall defects is important, but difficult when the extent of invasion is large. CASE PRESENTATION: A 34-year-old male was referred to our hospital with abdominal pain and diagnosed with obstructive transverse colon cancer. He had undergone ileo-sigmoid colostomy at his previous hospital. The tumor was massive and invaded the abdominal wall (maximum diameter: approximately 12 cm), and was accompanied by regional lymph node swelling. No distant metastasis was detected. We diagnosed the tumor as cT4bN2bM0 Stage IIIC locally advanced transverse colon cancer and planned neoadjuvant chemotherapy. After two courses of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan), he developed an entero-cutaneous fistula due to tumor penetration and required emergency diverting ileostomy construction. After the procedure, contrast-enhanced computed tomography showed good tumor shrinkage. As a result, the planned chemotherapy was canceled and he underwent radical resection of the tumor. En bloc extended right hemicolectomy was performed with excision of the fistula, ensuring a sufficient margin. The post-excision defect at the anterior abdominal wall involved 11 × 16 cm of fascia and 6 × 9 cm of skin located in the middle of the abdomen. A free anterolateral thigh flap was harvested from the right thigh and vascular pedicle was anastomosed to the right gastroepiploic artery and vein. The fascia lata, which was included in the anterolateral thigh flap, was sutured onto the abdominal wall fascia as inlay fashion to reconstruct the abdominal wall defect. Histopathology revealed moderately differentiated adenocarcinoma of the colon with no tumor cells in the abdominal wall tissue [post-chemotherapeutic state, therapy effect: Grade 1b; Stage IIA (ypT3N0M0)]. All resected margins of the specimen were free from adenocarcinoma. He was discharged on postoperative day 16. CONCLUSION: We report a case of colon cancer extensively invading the abdominal wall, which was completely resected. The abdominal wall defect was reconstructed with a free anterolateral thigh flap after tumor shrinkage with neoadjuvant chemotherapy. We present an efficient strategy for managing locally advanced colon cancer with extensive abdominal wall invasion.
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Background: Controversy persists about neoadjuvant chemotherapy (NAC) within the field of locally advanced colon cancer (LACC). The purpose of this study was to assess the existing and latest literature with high quality to determine the role of NAC in various aspects. Methods: A comprehensive literature search of the PubMed, Embase, Web of Science, and the Cochrane Library databases was conducted from inception to April 2022. Review Manager 5.3 was applied for meta-analyses with a random-effects model whenever possible. Results: Overall, 8 studies were included in this systematic review and meta-analysis, comprising 4 randomized controlled trials (RCTs) and 4 retrospective studies involving 40,136 participants. The 3-year overall survival (OS) (HR: 0.90, 95% CI: 0.66-1.23, P = 0.51) and 5-year OS (HR: 0.89, 95% CI: 0.53-1.03, P = 0.53) were comparable between two groups. Mortality in 30 days was found less frequent in the NAC group (OR: 0.43, 95% CI: 0.20-0.91, P = 0.03), whereas no significant differences were detected concerning other perioperative complications, R0 resection, or adverse events. In terms of subgroup analyses for RCTs, less anastomotic leak (OR: 0.51, 95% CI: 0.31-0.86, P = 0.01) and higher R0 resection rate (OR: 2.35, 95% CI: 1.04-5.32, P = 0.04) were observed in the NAC group. Conclusions: NAC is safe and feasible for patients with LACC, but no significant survival benefit could be demonstrated. The application of NAC still needs to be prudent until significant evidence supporting the oncological outcomes is presented. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022333306).
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INTRODUCTION: With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. MATERIALS AND METHODS: From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). RESULTS: In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23-60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. CONCLUSION: Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies.