Resection Of Primary Colorectal Cancer Research Articles

Deep learning for prediction of colorectal cancer outcome: a discovery and validation study

Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72-5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07-4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes. The Research Council of Norway.

Management of isolated para-aortic lymph node recurrence after surgery for colorectal cancer.

PurposeThe rare incidence of isolated para-aortic lymph node (PALN) recurrence of colorectal cancer has precluded the formulation of treatment guidelines. This study evaluated and compared the effects of different treatment modalities on survival outcomes in patients with PALN recurrence.MethodsPatients diagnosed with isolated PALN recurrence after curative resection for primary colorectal cancer from January 2004 to December 2014 were evaluated retrospectively. Patients with isolated recurrence were selected using imaging modalities. Overall survival (OS) and survival after recurrence (SAR) were analyzed and compared between different treatments using the Kaplan-Meier method.ResultsThe median OS was 64 months with a median follow-up time of 50 months. Of the 46 patients with PALN recurrence, 35 (76.1%) had isolated recurrences. Of these 35 patients, 16 underwent PALN resection and 19 received chemotherapy. Median SAR was significantly longer in patients who did than did not undergo resection (71 months vs. 39 months, P = 0.017). Median OS tended to be longer in patients who did than did not undergo resection (77 months vs. 62 months, P = 0.055). SAR was similar in patients who received radiotherapy and those who underwent resection (34 months vs. 46 months, P = 0.146). Three of 16 patients (18.8%) who underwent resection were found to be recurrence-free.ConclusionSurgical resection of isolated PALN recurrence may benefit patients, with favorable survival outcomes and by providing definitive diagnosis for proper treatment planning.

Simultaneous Laparoscopic Resection of Primary Colorectal Cancer and Associated Liver Metastases: A Systematic Review

Simultaneous Laparoscopic Resection of Primary Colorectal Cancer and Associated Liver Metastases: A Systematic Review

Circulating tumour DNA in early stage colorectal cancer: can blood tell all?

The decision to offer adjuvant chemotherapy after primary resection for non-metastatic colorectal cancer (CRC) is principally guided by histopathologic parameters. However, this approach lacks precision with many patients potentially receiving unnecessary treatment. For example, only about 1 in 20 patients with stage II colon cancer will benefit from adjuvant chemotherapy (1). In large part, this is due to the lack of prognostic biomarkers to precisely stratify patient risk and to guide a personalised approach to treatment. Additionally, for the past 15 years there has been no progress in developing more effective adjuvant therapy beyond oxaliplatin and fluoropyrimidine (2-6).

Necessity of Genetic Evaluation of Metachronous Metastases of Colorectal Cancer: Quantitative Analysis of Genetic Discordance Between Metachronous Metastases and Radically Resected Primary Colorectal Cancers Using Next-Generation Sequencing

Mutation analyses provide the basis of selecting an appropriate target agent for the treatment of metastatic colorectal cancer. However, metachronous metastases developed after the treatment of primary tumor could create significant opportunities for different genetic profiles relative to the primary tumors. The purpose of this study was to assess the necessity of genetic evaluation of metachronous metastases; we performed a quantitative analysis of genetic discordance between metachronous metastases and radically resected primary colorectal cancers using next-generation sequencing. This was a retrospective study. Patients from a single-institution tertiary care center were studied. We enrolled 33 patients who underwent resection of metachronous metastases between January 2014 and December 2016, ≥6 months after radical resection of primary colorectal cancer and whose tissue was available for analysis. Tumor samples were analyzed by next-generation sequencing. The mutant allele frequency was analyzed to evaluate the proportion of mutations in the tumor tissue. The mutant allele frequency of KRAS in metachronous metastases was higher in 6 cases (mean difference =% 25.5% (range, 9.5%-58.0%)) and lower in 3 cases (mean difference = 9.3% (range, 8.0-10.0%) compared with each of their primary tumors. In 1 case, the KRAS mutant-type (mutant allele frequency = 22.6%) metachronous metastasis had developed from the KRAS wild-type primary tumor. Tumor sample may not represent perfectly the whole tumor of the patient because of heterogeneity. Genetic discordance can exist between metachronous metastases and radically resected primary colorectal cancers. For appropriate target therapy, genetic evaluation of metachronous metastases needs to be considered when possible. See Video Abstract at http://links.lww.com/DCR/A932.

Clinicopathological and mutational analyses of colorectal cancer with mutations in the POLE gene.

Here, we investigated the clinicopathological and mutation profiles of colorectal cancer (CRC) with POLE mutations. Whole‐exome sequencing was performed in 910 surgically resected primary CRCs. Tumors exceeding 500 counts of nonsynonymous single nucleotide variants (SNVs) were classified as hypermutators, whereas the remaining were classified as nonhypermutators. The hypermutators were subdivided into 2 groups. CRCs harboring more than 20% C‐to‐A and less than 3% C‐to‐G transversions were classified as POLE category tumors, whereas the remaining were classified as common‐hypermutators. Gene expression profiling (GEP) analysis was performed in 892 (98.0%) tumors. Fifty‐seven (6.3%) and 10 (1.1%) tumors were classified common‐hypermutators and POLE category tumors, respectively. POLE category tumors harbored a significantly higher SNV count than common‐hypermutators, and all POLE category tumors were associated with exonuclease domain mutations, such as P286R, F367C, V411L, and S297Y, in the POLE gene. Patients with POLE category tumors were significantly younger than those with nonhypermutators and common‐hypermutators. All POLE mutations in the early‐onset (age of onset ≤50 years old) POLE category (7 tumors) were P286R mutations. GEP analysis revealed that PD‐L1 and PD‐1 gene expression levels were significantly increased in both common‐hypermutators and POLE category tumors compared with those in nonhypermutators. CD8A expression was significantly upregulated in POLE category tumors compared with that in nonhypermutators. Thus, we concluded that CRCs with POLE proofreading deficiency had characteristics distinct from those of other CRCs. Analysis of POLE proofreading deficiency may be clinically significant for personalized management of CRCs.

Simultaneous resection of primary colorectal cancer and its liver metastases: why not?

In patients with colorectal cancer and synchronous liver metastases the issue of performing a simultaneous resection of both the primary tumour and the liver metastases is a matter of much debate, especially among surgeons. The study by Howard et al . provides relevant information and is a nice reflection of general daily practice decision making in the Canadian surgical community (1).

The Disease-Free Interval Between Resection of Primary Colorectal Malignancy and the Detection of Hepatic Metastases Predicts Disease Recurrence But Not Overall Survival

IntroductionThe disease-free interval (DFI) between resection of primary colorectal cancer (CRC) and diagnosis of liver metastases is considered an important prognostic indicator; however, recent analyses in metastatic CRC found limited evidence to support this notion.ObjectiveThe current study aims to determine the prognostic value of the DFI in patients with resectable colorectal liver metastases (CRLM).MethodsPatients undergoing first surgical treatment of CRLM at three academic centers in The Netherlands were eligible for inclusion. The DFI was defined as the time between resection of CRC and detection of CRLM. Baseline characteristics and Kaplan–Meier survival estimates were stratified by DFI. Cox regression analyses were performed for overall (OS) and disease-free survival (DFS), with the DFI entered as a continuous measure using a restricted cubic spline function with three knots.ResultsIn total, 1374 patients were included. Patients with a shorter DFI more often had lymph node involvement of the primary, more frequently received neoadjuvant chemotherapy for CRLM, and had higher number of CRLM at diagnosis. The DFI significantly contributed to DFS prediction (p =0.002), but not for predicting OS (p =0.169). Point estimates of the hazard ratio (95% confidence interval) for a DFI of 0 versus 12 months and 0 versus 24 months were 1.284 (1.114–1.480) and 1.444 (1.180–1.766), respectively, for DFS, and 1.111 (0.928–1.330) and 1.202 (0.933–1.550), respectively, for OS.ConclusionThe DFI is of prognostic value for predicting disease recurrence following surgical treatment of CRLM, but not for predicting OS outcomes.

Nationwide outcomes of simultaneous resection of primary colorectal cancer and synchronous liver metastases

Nationwide outcomes of simultaneous resection of primary colorectal cancer and synchronous liver metastases

Risk factors affecting hospital stay among patients undergoing colon cancer surgery: a prospective cohort study.

To identify and validate risk factors that contribute to prolonged length of hospital stay (LOS) in patients undergoing resection for colorectal cancer. This prospective cohort study included 1955 patients admitted to 22 hospitals for primary resection of colorectal cancer. Multivariate analyses were used to identify and validate risk factors, randomizing patients into a derivation and a validation cohort. Multiple correspondence and cluster analysis were performed to identify clinical subtypes based on LOS. The strongest independent predictors of prolonged LOS were postoperative reintervention, surgical site infection, open surgery, and distant metastasis. The multiple correspondence and cluster analysis provided three groups of patients in relation to prolonged LOS: patients with the longest LOS included the highest percentage of patients with open surgery, distant metastasis, deep surgical site infections, emergency admissions, additional diagnostic factors, and highly contaminated surgical sites. Patients with prolonged LOS (> 14days) were more likely to develop adverse outcomes within 30days after discharge. Patients undergoing resection of colorectal cancer cluster into different groups based on LOS of the index admission. Those with prolonged LOS were more likely to develop adverse outcomes within 30days after discharge. Some of the strongest independent predictors of prolonged LOS, such as surgical infections or open surgery, could be modified to reduce LOS and, in turn, other adverse outcomes. NCT02488161.

Assessment of systemic and metastatic neutrophilic inflammation in synchronously resected colorectal cancer and liver metastases.

534 Background: Immunotherapy has proven a largely ineffective treatment for MMR proficient colorectal cancer (CRC). Resistance to immunotherapy is due to the immunosuppressive microenvironment of colorectal cancer, with CMS4 disease proving most aggressive. Using a cohort of synchronously resected CRC and metastases we examine the relationships between common immune cells in the circulation and microenvironment of primary and secondary CRC to assess microenvironmental determinants of outcome in metastatic CRC. Methods: 46 patients that had synchronous resection of primary CRC and liver metastasis at Glasgow Royal Infirmary were included. The relationships between Neutrophil lymphocyte ratios (NLR), tissue MPO and CXCR2 positive neutrophils, CD68 positive macrophages, and CD8 positive effector T cells and Klintrup-Makinen (KM) scores were quantified. Results: There was correlation between MPO and CXCR2 positive neutrophils (r = 0.668, P = 0.014) within metastases and both of these factors were independently associated with poor outcome ( P &lt; 0.001, P = 0.002 respectively). High CD8+ T cells numbers and KM grade in both primary and metastatic niches were independently associated with better outcome following synchronous resection (P &lt; 0.01). High systemic neutrophil counts (NLR) were associated with poor outcome in patients having synchronous resection (P = 0.001) and correlated with neutrophil numbers in metastases (r = 0.329, P = 0.05). MPO (P &lt; 0.001) and CXCR2 (P = 0.004) positive neutrophils within the metastatic niche and KM grade of the primary tumour (P = 0.002) remained negative prognostic indicators on multivariate analysis. Conclusions: While CD8+ T cells impact positively on prognosis, the negative impact of neutrophils within the metastatic niche is the strongest determinant of outcome in synchronously resected CRC. This study raises questions as to the heterogeneity of neutrophils within primary and metastatic colorectal cancer and whether negatively prognostic neutrophils can be phenotyped and therapeutically targeted.

One-stage pure laparoscopic resection of primary colorectal cancer and synchronous hepatic metastases: a single institution experience

One-stage pure laparoscopic resection of primary colorectal cancer and synchronous hepatic metastases: a single institution experience

One-stage pure laparoscopic resection of primary colorectal cancer and synchronous hepatic metastases: a single institution experience

Background: Simultaneous pure laparoscopic resection (SPLR) of the primary colorectal cancer and synchronous liver metastases (LM) is rarely performed. The aim of this study is to review a single institution experience. Methods: Between 2012 and 2016, 64 patients underwent laparoscopic liver resection for various benign and malignant liver tumors. The analysis included SPLR. The primary outcomes of this study were clinical and pathological variables. The secondary outcome was survival. Results: Eight patients underwent SPLR with laparoscopic colectomy (n = 3) and proctectomy (n = 5). Liver resections included only minor surgery: left lateral sectionectomies (n = 4) and atypical resections (n = 4). Average operating time was 270 minutes (range 180 - 390 minutes). Estimated blood loss was in average 380 mL (range 50-600 mL). Conversion to open procedure was performed in one patient. All patients had only one LM and the size was in average 2.6 cm (range 1 – 5 cm). R0 resection was achieved in all cases. Resection margin was in average 6.8 mm (range 2-15 mm). Median (range) hospital stay was 9 (7-42) days. The number of major morbidity was: 1 (Clavien-Dindo 3B), and there was no postoperative mortality. Median follow-up for surviving patients was 13 months. Six patients are alive with no evidence of disease, one patient is alive with disease and one patient died of disease. Conclusion: SPLR is feasible and safe for treatment of synchronous LM and there is no compromise of oncological surgical principles.

Which strategy is better for resectable synchronous liver metastasis from colorectal cancer, simultaneous surgery, or staged surgery? Multicenter retrospective analysis.

PurposeThe optimal treatment for synchronous liver metastasis (LM) from colorectal cancer (CRC) depends on various factors. The present study was intended to investigate the oncologic outcome according to the time of resection of metastatic lesions.MethodsData from patients who underwent treatment with curative intent for primary CRC and synchronous LM between 2004 and 2009 from 9 university hospitals in Korea were collected retrospectively. One hundred forty-three patients underwent simultaneous resection for primary CRC and synchronous LM (simultaneous surgery group), and 65 patients were treated by 2-stage operation (staged surgery group).ResultsThe mean follow-up length was 41.2 ± 24.6 months. In the extent of resection for hepatic metastasis, major hepatectomy was more frequently performed in staged surgery group (33.8% vs. 8.4%, P < 0.001). The rate of severe complications of Clavien-Dindo classification grade III or more was not significantly different between the 2 groups. The 3-year overall survival (OS) rate was 85.0% in staged surgery group and 69.4% in simultaneous surgery group (P = 0.013), and the 3-year recurrence-free survival (RFS) rate was 46.4% in staged surgery group and 30.2% in simultaneous surgery group (P = 0.143). In subgroup analysis based on the location of primary CRC, the benefit of staged surgery for OS and RFS was clearly shown in rectal cancer (P = 0.021 and P = 0.015).ConclusionBased on our results, staged surgery with or without neoadjuvant chemotherapy should be considered for resectable synchronous LM from CRC, especially in rectal cancer, as a safe and fairly promising option.

Standardize the Surgical Technique and Clarify the Relevant Anatomic Concept for Complete Mobilization of Colonic Splenic Flexure Using da Vinci Xi® Robotic System.

The present study is to set up a standardized approach for complete mobilization of colonic splenic flexure using da Vinci Xi® robotic system, based on clarification of the mesenteric structures of distal transverse colon. The surgical outcomes and relevant anatomic structures of 104 consecutive patients undergoing robotic resection of primary colorectal cancer with the intent of complete mobilization of colonic splenic flexure using da Vinci Xi® robotic system were retrospectively reviewed. Complete mobilization of colonic splenic flexure can be efficiently performed by the Xi® robotic system, as demonstrated by short operation time, minimal intra-operative blood loss, and few surgical complications. Xi® robotic system has overcome the drawbacks of Si® robotic system for the mobilization of colonic splenic flexure. The present study defined the following anatomic hallmarks for the colonic splenic flexure: (1) The transverse mesocolon distal to the inferior mesenteric vein adheres to the low border of pancreas by the avascular fibrous connective tissues, which have been inappropriately named as "mesenteric root"; (2) The colonic splenic flexure abuts closely to spleen with an acute angle in 78.85% (n = 82/104); (3) Only a minority of patients presented with the Riolan branch (15.38%, n = 16/104) or the Moskowitz artery (8.65%, n = 9/104). With increased maneuverability of Xi® robotic arms and the clarification of relevant anatomic concept, the surgical technique for the complete mobilization of colonic splenic flexure can be standardized; and the standardization of surgical technique is the first step toward the enhanced automation in the rapidly evolving robotic systems.

Is laparoscopic simultaneous resection of primary colorectal cancer and liver metastases beneficial

Laparoscopic colorectal resection (LCR) and laparoscopic liver resection (LLR) for selected patients with colorectal cancer and colorectal liver metastases (CRLM) has become a universal treatment, respectively (1,2). If a laparoscopic approach can be applied, less intraoperative blood loss, decreased morbidity, and faster recovery is expected compared to an open approach (3,4).

Is laparoscopic simultaneous resection of primary colorectal cancer and liver metastases beneficial?

Is laparoscopic simultaneous resection of primary colorectal cancer and liver metastases beneficial?

605TiP - Phase II study of resection of primary colorectal cancer and synchronous liver metastasis after S-1 + oxaliplatin (SOX) + bevacizumab (Bmab) therapy and adjuvant S-1 chemotherapy

605TiP - Phase II study of resection of primary colorectal cancer and synchronous liver metastasis after S-1 + oxaliplatin (SOX) + bevacizumab (Bmab) therapy and adjuvant S-1 chemotherapy

To determine if there is a difference in outcomes for patients undergoing synchronous primary colorectal cancer and liver resection with or without preoperative treatment

To determine if there is a difference in outcomes for patients undergoing synchronous primary colorectal cancer and liver resection with or without preoperative treatment

Comparison of short and long-time outcomes between laparoscopic and conventional open multivisceral resection for primary T4b colorectal cancer

This study aimed to compare laparoscopic multivisceral resection (LMVR) with conventional open multivisceral resection (OMVR) for primary T4b colorectal cancer (CRC) in short and long-time outcomes. Patients receiving LMVR or OMVR for primary T4b CRC from January 2009 to June 2016 were enrolled. Patients' clinicopathological characteristics and survival data were collected and analyzed. Multivariable analysis was performed to find the factors related with survival. All statistical analysis was performed by SPSS 22.0. A total of 91 patients (LMVR 38, OMVR 53) were included in this study. Patients undergoing LMVR were associated with smaller incision length (P<0.001), less blood loss (P=0.01) and comparable operative time (P=0.071). Patients in LMVR group also had less time to first flatus (P=0.025). The results also suggested LMVR could reduce the incidence of postoperative complication. The conversion rate was 28.9%. The 3-year OS was 64.2%, 68.4% in OMVR, LMVR group respectively and the 3-year DFS was 56.6%, 52.6% in OMVR, LMVR group respectively. The Kaplan curves demonstrated that LMVR group had similar OS (P=0.896) and DFS (P=0.806) when compared with OMVR group. In addition, the multivariate analysis demonstrated that laparoscopic surgery was not associated with poorer survival. Not all MVR for T4b CRC should be performed by open procedure, LMVR can be safe and feasible for primary T4b CRC in selected patients. It can faster the postoperative recovery and reduce the incidence of postoperative complication. The OS and DFS are also not inferior to open group.