Resection Of Primary Colorectal Cancer Research Articles

Cumulative operative time and postoperative complication risk in synchronous resections of colorectal liver metastases and primary tumors

Presenter: Allison N Martin MD, MPH | The University of Texas MD Anderson Cancer Center Background: Selection of patients for synchronous resection of colorectal liver metastases (CLM) and primary colorectal cancers (CRC) is complex due to inherent complication rates. We sought to identify perioperative factors associated with postoperative morbidity after synchronous resection. Methods: Using a prospectively maintained quality improvement database, adult patients undergoing synchronous CLM and CRC resection from 1/1/2017-7/1/2020 were included, and 90-day postoperative outcomes were collected. The primary outcome of this study was to estimate effects of clinical covariates on the occurrence of grade 2 or worse (grade ≥2) complications as defined by the Accordion Severity Grading System. Univariate and sequential multivariable logistic regression models were used to estimate the impact of colorectal resection type, Kawaguchi-Gayet complexity grade of hepatectomy and perioperative risk factors on outcomes, including 90-day postoperative complications. Results: A total of 120 patients underwent synchronous CLM and CRC resection during this study period. Most patients (62%) underwent a low-complexity hepatectomy (Kawaguchi-Gayet 1 [KG1]), and the most common CRC resections were right colectomy (n=37, 31%) and proctectomy (n=40, 33%). The most common synchronous resection was a KG1 CLM resection with proctectomy (n=30, 25%). Nearly 40% (n=46) of patients experienced grade ≥2 complications, and 12% (n=14) experienced grade ≥3 complications. Grade ≥2 complication was associated with longer length of stay (median LOS 7.5 vs. 4 days, p506 minutes) had higher rates of grade ≥2 complications (37% vs. 15%, p=0.04) and were associated with a greater than 4-fold increased risk of grade ≥2 morbidity (OR 4.3, 95% CI 1.41-13.1, p=0.01). As an intraoperative surrogate for complexity of hepatectomy, Pringle inflow occlusion time above the median (33 minutes) was not significantly associated with increased risk of grade ≥2 morbidity (p=0.26). In multivariable analysis, increasing operative time was independently associated with grade ≥2 complications, especially for those resections in the highest quartile (OR 7.28, 95% CI 1.73-30.6, p=0.007; Table 1). Conclusion: In patients preoperatively selected for synchronous CLM and CRC resection, prolonged operative time is independently associated with grade ≥2 complications. Surgical teams should consider preoperative initiatives to address factors related to total operative time, including team dynamics, communication, and case selection, to accurately predict and reduce cumulative operative time as a strategy to mitigate complication risk. Operative time may also inform intraoperative decisions after the hepatectomy to continue with or delay the colorectal resection.

Deep learning model for the prediction of microsatellite instability in colorectal cancer: a diagnostic study.

Detecting microsatellite instability (MSI) in colorectal cancer is crucial for clinical decision making, as it identifies patients with differential treatment response and prognosis. Universal MSI testing is recommended, but many patients remain untested. A critical need exists for broadly accessible, cost-efficient tools to aid patient selection for testing. Here, we investigate the potential of a deep learning-based system for automated MSI prediction directly from haematoxylin and eosin (H&E)-stained whole-slide images (WSIs). Our deep learning model (MSINet) was developed using 100 H&E-stained WSIs (50 with microsatellite stability [MSS] and 50 with MSI) scanned at 40× magnification, each from a patient randomly selected in a class-balanced manner from the pool of 343 patients who underwent primary colorectal cancer resection at Stanford University Medical Center (Stanford, CA, USA; internal dataset) between Jan 1, 2015, and Dec 31, 2017. We internally validated the model on a holdout test set (15 H&E-stained WSIs from 15 patients; seven cases with MSS and eight with MSI) and externally validated the model on 484 H&E-stained WSIs (402 cases with MSS and 77 with MSI; 479 patients) from The Cancer Genome Atlas, containing WSIs scanned at 40× and 20× magnification. Performance was primarily evaluated using the sensitivity, specificity, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUROC). We compared the model's performance with that of five gastrointestinal pathologists on a class-balanced, randomly selected subset of 40× magnification WSIs from the external dataset (20 with MSS and 20 with MSI). The MSINet model achieved an AUROC of 0·931 (95% CI 0·771-1·000) on the holdout test set from the internal dataset and 0·779 (0·720-0·838) on the external dataset. On the external dataset, using a sensitivity-weighted operating point, the model achieved an NPV of 93·7% (95% CI 90·3-96·2), sensitivity of 76·0% (64·8-85·1), and specificity of 66·6% (61·8-71·2). On the reader experiment (40 cases), the model achieved an AUROC of 0·865 (95% CI 0·735-0·995). The mean AUROC performance of the five pathologists was 0·605 (95% CI 0·453-0·757). Our deep learning model exceeded the performance of experienced gastrointestinal pathologists at predicting MSI on H&E-stained WSIs. Within the current universal MSI testing paradigm, such a model might contribute value as an automated screening tool to triage patients for confirmatory testing, potentially reducing the number of tested patients, thereby resulting in substantial test-related labour and cost savings. Stanford Cancer Institute and Stanford Departments of Pathology and Biomedical Data Science.

Risk Stratification Based on Synchronous Neoplasia and Clinical Physicochemical Characteristics Predicts a Higher Incidence of Metachronous Advanced Neoplasia in Patients Undergoing Colorectal Resection for Colorectal Cancer.

PurposePatients who undergo primary colorectal cancer (CRC) resection remain at increased risk for metachronous advanced neoplasia (MAN) in the remnant colorectum. This study aimed to investigate the incidence and clinicopathological characteristics predictive of MAN development in the residual colon after surgery.Patients and MethodsWe retrospectively reviewed 450 primary CRC cases referred to our hospital during a 4-year period. Univariate and multivariate analyses were performed to identify risk factors for MAN. The cumulative incidence of MAN was evaluated by the Cox proportional hazards model.ResultsMAN development was confirmed in 78 of the 450 patients (17.3%). Overall 1-, 2-, 3-, and 5-year cumulative probabilities were 0.9%, 4.8%, 9.8%, and 16.1%, respectively, for MAN. Among the clinical and colonoscopic factors at baseline, the independent factors that were significantly associated with MAN were synchronous neoplasia, carcinoembryonic antigen (CEA) level ≥10.0 ng/mL, and index cancer size ≥50 mm. The cumulative probability of MAN was significantly higher for patients with synchronous advanced neoplasia (SAN) than for those without synchronous neoplasia (P = 0.000). A subgroup analysis of patients based on the CEA level and index cancer size indicated that CEA ≥10 ng/mL and index cancer ≥50 mm resulted in a significantly higher cumulative probability of MAN (P = 0.039).ConclusionPatients with SAN or high preoperative serum CEA levels and large index cancer are at increased risk for early-onset MAN. More intensive surveillance strategies may be appropriate for these groups. Risk stratification based on synchronous neoplasia and clinical physicochemical characteristics requires further investigations involving modified appropriate postoperative colonoscopic surveillance schedules.

Exam 1: Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis

Exam 1: Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001). From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.

Abdominal lymph node recurrence from colorectal cancer: Resection should be considered as a curative treatment in patients with controlled disease

BackgroundLymph node recurrences (LNR) from colorectal cancer (CRC) still represent a therapeutic challenge, as standardized recommendations have yet to be established. The aim of this study was to analyze short- and long-term oncological outcomes following resection of LNR from CRC. MethodsAll patients with previously resected CRC who underwent histopathologically confirmed LNR resection in 3 tertiary referral centers between 2010 and 2017 were reviewed. Short- and long-term outcomes were analyzed, mainly recurrence-free and overall survival. Further recurrences following LNR resection were also analyzed. ResultsOverall, 18 patients were included. Primary CRC was left-sided in 16 (89%) patients, staged T3-4 in 15 (83%), N+ in 14 (78%) and presented with synchronous metastases in 8 (43%). Median time interval between primary CRC and LNR resections was 31 months. Performed lymphadenectomies were aortocaval (n = 10), pelvic (n = 7), in hepatic pedicle (n = 3) and mesenteric (n = 1). Four patients had associated liver metastases resection. Three (17%) presented with postoperative complications, of which one Clavien-Dindo 3. Fourteen (78%) patients presented with further recurrences after a mean delay of 9 months, with 36% of patients presenting with early (<6 months) recurrence. Five (36%) patients could undergo secondary recurrence resection and 3 (21%) patients radiotherapy. Median overall survival following LNR resection reached 44 months. ConclusionsCurrent results suggest that LNR resection is feasible and associated with improved survival, in selected patients. Longer time interval between primary CRC resection and LNR occurrence appeared to be a favorable prognostic factor whereas multisite recurrence appeared to be associated with impaired long-term survival.

Abstract 3331: Role of innate immune cells in the development of vessel co-opting CRC liver metastases

Abstract Approximatively 50 % of patients who undergo resection for primary colorectal cancer will develop liver metastases. Liver metastases present as two major histopathological growth patterns (HGP) the desmoplastic and the replacement HGP. In the desmoplastic HGP, the cancer cells are surrounded by a desmoplastic stromal ring preventing their contact with the normal liver. In the replacement HGP, the cancer cells infiltrate the normal liver and replace hepatocytes near the tumour periphery. We have found that the desmoplastic HGP tumors derive their blood supply through angiogenesis while the replacement HGP tumors are non-angiogenic and co-opt the blood vessel of the liver they invade. Furthermore, we have published that patients under chemotherapy presenting with a vessel co-opting phenotype have a worse pathological response and five-year overall survival compared to patients presenting with angiogenic liver metastases. Their prognosis is worse when treated with bevacizumab an anti-VEGF antibody used alongside chemotherapy. CRCLM are considered immunologically cold lesions, with low numbers of infiltrating T-cells, and thought to be unlikely to benefit from immunotherapies. We have recently found that neutrophils and macrophages but not lymphocytes infiltrate vessel co-opting lesions to a greater extent than angiogenic lesions. Using flow cytometry and the Nanostring GeoMx spatial protein profiling platform capable of detecting up to 96 proteins simultaneously on FFPE tissue slices, we established the immunoprofile of immune cells recruited to angiogenic or vessel co-opting CRCLM lesions in chemonaive and treated patients. Many studies have demonstrated that neutrophils and macrophages play an important role in tumor progression, modification of the ECM, angiogenesis, and immunosuppression. We hypothesize that innate immune cells can facilitate blood vessel co-option of CRCLM lesions and contribute to an immunosupressive environment favorable to tumor growth. Fully understanding the role of the innate immune system in the developmend of vessel co-opting CRCLM tumors could allow for the development of immunotherapies capable of converting vessel co-opting lesions into angiogenic lesions that are more successfully treated with chemotherapy and anti-angiogenic therapies. Citation Format: Thomas Z. Mayer, Diane H. Kim, Miran Rada, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos. Role of innate immune cells in the development of vessel co-opting CRC liver metastases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3331.

Abstract 6519: Patient, primary colorectal tumor and liver metastases factors which influence survival after liver metastasectomy and therefore should be considered at the preoperative tumor board

Abstract Aim of the study: Patients with colorectal liver metastases (CRLM) should be considered for liver surgery and this study illuminate important factors to be considered at the preoperative multidisciplinary tumor board. Background: Survival after surgical resection or ablation of colorectal liver metastases is increasingly favorable but only a minority of patients undergo curatively intended treatment. Several studies have shown the importance of assessing resectability by liver surgeons. Which prognostic factors to consider before liver surgery is not fully understood. Methods: The Swedish colorectal cancer registry (SCRCR) and the Swedish registry for liver tumors (SweLiv) were linked to identify radically resected primary colorectal cancer patients during the years 2009-2013 also surgically treated for liver metastases, synchronously or metachronously. CRLM characteristics and treatment strategies as well as primary tumor and patient factors were analyzed for prognostic impact. 5-year age-standardized relative survival (RS) and 5-year excess mortality rate ratio (EMRR) were calculated. Treatment with ablation only for tumors with maximum size of 30 mm was analyzed in a propensity score weighted cox regression. Results: 1325 patients were included in the study cohort, whereof 300 were 75 years or older. 1200 were treated with resection and 125 were treated with ablation only. Age-standardized relative five-year survival after open resection of colorectal liver metastases was 54.8 % (95 % CI: 50.6-58.7) and after ablation 32.4 % (95 % CI: 23.3-41.9). Multivariate analysis identified age ≥75 years, tumor size &amp;gt;20 mm, location in segment 4, 6, 7 or 8, multiple metastatic sites and progress after chemotherapy as important risk factors with more than 25 % higher EMRR. Only when analyzed without segments included in the multivariate model was the number of metastases a significant risk factor. Vascular invasion, lymph node ratio and complications at time of primary tumor resection were also important negative prognostic factors. Ablation of small metastases compared to resection was a significant risk factor (HR 2.25 (95 % CI 1.61-3.15)). Conclusion: Tumor size over 20 mm and location of metastases as well as lymph node status and complications after resection of the primary tumor are important risk factors for survival outcome after liver surgery of CRLM. Progress after preoperative chemotherapy and ablation compared to resection more than doubled the risk of death within 5 years. Citation Format: Peter Scherman, Peter Naredi, Ingvar Syk, Erik Holmberg, Magnus Rizell. Patient, primary colorectal tumor and liver metastases factors which influence survival after liver metastasectomy and therefore should be considered at the preoperative tumor board [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6519.

P-133 Extramural venous invasion detected with an elastin stain is a powerful predictor of cancer-specific mortality in STAGE I-IIIB resected colorectal cancer

Extramural venous invasion (EMVI) is considered an indicator of poor prognosis in patients who have undergone resection of primary colorectal cancer (CRC), but its use has not been widely adopted in staging systems or nomograms. In particular, EMVI is not reported in most large case series, is not included in most large CRC databases, and is not incorporated into the current AJCC TNM staging system. Staining for elastin may facilitate the accurate detection of EMVI and minimize inter-observer variability. We examined the prognostic potential of EMVI detected by elastin staining at a tertiary center that performs a high volume of CRC resections. This is a single-institution, observational study of consecutive patients who underwent resection of primary CRC between 01/01/2011 and 31/12//2016. All pathology specimens were re-assessed by reviewers who were blinded to patient outcomes. Venous invasion was detected using an elastin trichrome stain and classified as Intramural or Extramural. Overall and disease-specific survival (OS, DSS) were estimated using the Kaplan-Meier method. Differences between groups were assessed using the Mantel-Cox log-rank test. For the present analysis, we excluded all patients with stage IV (n=80) or IIIC (n=34) CRC. The cohort for analysis included 428 patients (248M, 190F; AJCC 8th edition Stage I n=107; Stage II n=185; Stage IIIA and B n=146) with a median follow-up time of 61 months (0.1-104). For the entire cohort, OS and DSS at 5 years were 82% and 90%, respectively. AJCC stage (p=0.04), but not T stage (p=0.08) or N stage (p=0.09), was prognostic of DSS. Neither grade (p=0.1) nor IMVI (p=0.4) were prognostic, whereas EMVI was highly prognostic of inferior DSS (p< 0.001). In this cohort of Stage I - III CRC patients with complete follow-up, EMVI as assessed by elastin staining was a powerful predictor of death from CRC. Elastin staining, which improves the accuracy and objectivity of EMVI detection, may allow validation of EMVI as an independent prognostic variable that should be incorporated into staging systems and nomograms. Accurate assessment of EMVI would permit refinement of risk estimation, and inform individualized decision-making regarding adjuvant therapy in patients who have undergone resection of CRC.

Physical Activity In Colorectal Cancer Patients 12 Months After Resection: Results From The Colocare Study

While several studies have objectively measured physical activity (PA) and sedentary behavior (SB) in colorectal cancer survivors, the time between cancer diagnosis and accelerometer wear within these studies was highly variable. PURPOSE: To quantify PA and SB in colorectal cancer survivors at a fixed time-point (12 months) after primary tumor resection. METHODS: The ColoCare Study is an international, longitudinal, prospective cohort study in newly-diagnosed colorectal cancer patients that collects questionnaires and biospecimens at regular intervals from diagnosis to 5 years post-resection. For this analysis, participants with stage I-III colorectal cancer from the German Cancer Research Center (DKFZ, Heidelberg, Germany) and the Huntsman Cancer Institute (HCI, Salt Lake City, UT) were provided an Actigraph GT3X+ accelerometer 12 months after primary resection and asked to wear the monitor 24 hours per day for 4+ consecutive days. PA volume and intensity were derived from raw accelerometer data using ActiLife software (v6.16.3) and Freedson (1998) activity cut-points. Pearson correlations were used to evaluate associations between PA, SB, and clinicodemographic characteristics (e.g. BMI). RESULTS: Sixty-eight ColoCare participants (DKFZ n=43; HCI n=25) met valid accelerometer wear criteria (>10 h/day for 4+ days) at the 12 month time-point and were thus included in analysis. Participants spent 8.2 ± 5.8% of monitor wear time in moderate-to-vigorous physical activity (MVPA) and 73.3 ± 9.7% of monitor wear time sedentary. Additionally, participants accrued 168 ± 243 weekly exercise minutes (MVPA in bouts >10 minutes) and 38% were meeting the PA guidelines. Participants enrolled at HCI were significantly more active than those enrolled at the DKFZ (Steps/day: 10,008 ± 2,947 vs.6,188 ± 3,815, p<0.05) and those patients who did not receive adjuvant chemotherapy were more active than those who underwent chemotherapy (Steps/day: 8,585 ± 4,160 vs. 6,350 ± 3,349; p<0.05). CONCLUSIONS: PA levels 12 months after primary colorectal cancer resection were greater than expected, and may be influenced by geographic location and adjuvant chemotherapy use. Supported by the ACSM Paffenbarger-Blair Fund for Physical Activity Epidemiology, the Lackas Foundation, and NIH U01 CA206110

Efficacy analysis on laparoscopic simultaneous resection of primary colorectal cancer and liver metastases

Objective: To investigate the short-term outcomes of laparoscopic simultaneous resection of primary colorectal cancer and liver metastases in patients with resectable synchronous colorectal liver metastases (SCRLM). Methods: A descriptive case series study was performed. Clinicopathological data of patients with SCRLM who underwent laparoscopic simultaneous resection of colorectal cancer and liver metastases in Zhongshan Hospital between December 2015 and September 2018 were retrieved from a prospective colorectal cancer database. Perioperative presentations and short-term outcomes were analyzed. Results: A total of 53 patients were enrolled with average age of(61.7±11.3) years. Among them, 32 were male (60.4%) and 21 were female (39.6%). Twenty-five patients (47.2%) were American Society of Anesthesiologists (ASA) grade I and 28 (52.8%) were grade II. All the patients completed laparoscopic simultaneous resection without conversion. The average operation time was (320.2±114.5) min. The estimated blood loss was 150.0 (45.0-2000.0) ml, and only 2 cases (3.8%) received intraoperative transfusion. Postoperative pathologic results revealed that the average primary tumor size was (5.4±1.9) cm; 4 cases (7.5%) were T1-2 stage and 48 cases (90.6%) were T3-4 stage; 40 patients (75.5%) had lymph node metastasis; 19 (35.8%) had vascular involvement; 24 (45.3%) had neural invasion. The median number of liver metastases was 1.0 (1-8), and the average size of largest liver metastases was (3.0±1.9) cm. The median margin of liver metastases was 1.0 (0.1-3.5) cm, and only 1 case was R1 resection. The average time to the first postoperative flatus was (67.9±28.9) h, and the average time to the liquid diet was (107.0±33.8) h. The average postoperative indwelling catheterization time was (85.6±56.4) h. The average postoperative hospital stay was (9.2±4.4) d, and the average cost was (82±26) thousand RMB. No death within postoperative 30-day was found. The morbidity of postoperative complication was 32.1% (17/53) and 3 patients developed grade III to IV complications which were improved by conservative treatment. The median follow-up period was 23.2 months. During follow-up, 19 patients (35.8%) developed recurrence or metastasis, and 4 (7.5%) died. The 1- and 2-year disease-free survival (DFS) rates were 68% and 47% respectively, and the 1- and 2-year overall survival rates were 95% and 86% respectively. Conclusions: Laparoscopic simultaneous resection of primary colorectal cancer and liver metastases is safe and feasible in selected patients with SCRLM. Postoperative intestinal function recovery is enhanced, and morbidity and oncological outcomes are acceptable.

Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis

There is controversy over the best therapeutic approach for T1 colorectal cancer. We performed a systematic review and meta-analysis of long-term outcomes of endoscopic resection (ER) vs those of primary or additional surgery. We performed a systematic review of the PubMed, Embase, and Cochrane databases through October 2019 for studies that reported outcomes (overall survival, disease-specific survival, recurrence-free survival at 5 years, recurrence, and metastasis) of ER vs surgery in patients with colorectal neoplasms. Hazard ratios (HR) were calculated based on time to events. In total, 17 published studies with 19,979 patients were included. The median follow-up time among the studies was 36 months. The meta-analysis found no significant differences between primary ER and primary surgery in overall survival (79.6% vs 82.1%, HR, 1.10; 95% CI, 0.84-1.45), recurrence-free survival (96.0% vs 96.7%, HR, 1.28; 95% CI, 0.87-1.88), or disease-specific survival (94.8% vs 96.5%; HR, 1.09; 95% CI, 0.67-1.78). Additional surgery and primary surgery did not produce significant differences in recurrence-free survival (HR, 1.27; 95% CI, 0.85-1.89). A significantly lower proportion of patients who underwent primary ER had procedure-related adverse events (2.3%) than patients who underwent primary surgery (10.9%) (P < .001). Lymphovascular invasion and rectal cancer, but not depth of submucosal invasion, were independently associated with recurrence for all T1 colorectal cancers. In a systematic review and meta-analysis, we found that ER should be considered as the first-line treatment for endoscopically resectable T1 colorectal cancers. In cases of noncurative resection, additional surgery can have comparable outcomes to primary surgery.

A comparative study of total laparoscopic and laparoscopic-assisted simultaneous resection for colorectal cancer liver metastasis

Objective: To compare the safety and outcome between total laparoscopic and laparoscopy-assisted synchronous resection for colorectal cancer patients with liver metastases. Methods: The data of patients who underwent total laparoscopic or laparoscopy-assisted simultaneous resection of primary colorectal cancer and liver metastases in our hospital between December 2008 and December 2016 were collected and analyzed. The total laparoscopic surgery patients were matched 1∶2 to the laparoscopy-assisted surgery patients based on the propensity score. 22 patients were classified in the total laparoscopic group and 44 patients were classified in the laparoscopy-assisted group. The intraoperative conditions and postoperative outcomes of the two groups were compared. Results: There was no difference in the preoperative baseline data between the two groups (P>0.05). The median operative time were 317.50 and 267.50 minutes in the total laparoscopic group and the laparoscopy-assisted group, respectively, and the median intraoperative blood loss were 100 and 200 ml, both with no statistically significant differences (P>0.05). There were 1 case of intraoperative blood transfusion in the total laparoscopic group and 5 cases in the laparoscopy-assisted group, with no statistically significant difference (P=0.650). The median postoperative hospital stay in the two groups were 11.0 and 10.0 days, the median postoperative defecation time were 4.0 and 4.0 days and postoperative complication rates were 13.6% and 20.5%, and none of these differences were statistically significant (P>0.05). However, no Clavien-DindoⅡ level and above complications occurred in total laparoscopic group. The median disease-free survival (DFS) were 15.0 and 15.7 months in the total laparoscopic group and the laparoscopy-assisted group, the overall survival (OS) were 25.9 and 37.6 months, respectively, with no statistically significant differences (P>0.05). Conclusion: Laparoscopy-assisted approaches are similar, so the appropriate approach should be chosen according to the clinical condition and surgeon's experience.

Metastasis directed treatment of brain metastases from colorectal cancer – a Danish population-based cohort study

Background: Brain metastases (BMs) are an uncommon presentation of metastatic colorectal cancer (mCRC) with reported incidence of about 2–4%. Today, there is an increased awareness towards a metastasis directed treatment approach with either surgical resection, stereotactic radiotherapy (SRT) or both. We examined patient characteristics and survival for patients treated with a localized modality for BM from CRC in a nationwide population-based study.Methods: A registry-based cohort study of all patients with a resected primary colorectal cancer and localized treatment of BM during 2000–2013. We computed descriptive statistics and analysed overall survival by the Kaplan–Meier method and Cox regression.Results: A total of 38131 patients had surgery for a primary CRC and 235 patients were recorded with a metastasis directed treatment for BM, comprising resection alone (n = 158), SRT alone (n = 51) and combined resection and SRT (n = 26). Rectal primary tumor (48.9% vs. 36.2%, p < .001) and lung metastasectomy (11.9 vs 2.8%, p < .001) were more frequent in the BM group. The median survival of patients receiving localized treatment for BM was 9.6 months (95% confidence interval (CI) 7.2–10.8). The 1- and 5-year overall survival were 41.7% (95% CI 35–48%) and 11.2% (95% CI 6.9–16.3%). In multivariate analysis, nodal stage was associated with increased mortality with a hazard ratio of 1.63 (95% CI 1.07–2.60, p = .03) for N2 stage with reference to N0.Conclusion: We report a median overall survival of 9.6 months for patients receiving localized treatment for BM from CRC. Lung metastases and rectal primary tumor are more common in the population treated for BM.

Trends in primary surgical resection and chemotherapy for metastatic colorectal cancer, 2000-2016.

e16000 Background: When, whether and in whom resection of the primary tumor for patients with metastatic colorectal cancer (CRC) is indicated remains incompletely elucidated, although a recent randomized trial (JCOG1007, presented at GI ASCO 2020) showed no survival benefit in resection of asymptomatic primary tumors in this population. Given the emergence of multiagent chemotherapy, surgery may be used less, but patterns of care for metastatic CRC have not been reported. As such, we sought to evaluate trends in use of primary surgical resection and chemotherapy among patients with metastatic CRC. Methods: Patients diagnosed with metastatic CRC between 2000-2016 were identified from the Surveillance, Epidemiology and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing primary surgical resection, with year of diagnosis as the primary independent variable. The cohort analysis was also stratified by primary site (colon versus rectum), age ( &lt; 50 vs. &gt;50 years) and whether patients also underwent resection of metastatic sites (yes versus no). The secondary endpoint of interest was receipt of any chemotherapy, also assessed by multivariable logistic regression. Results: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent resection of their primary tumor. The odds of undergoing primary surgery decreased with later year of diagnosis, with patients diagnosed in 2016 61.1% less likely to undergo surgery than those diagnosed in 2000 (AOR 0.39, 95% CI 0.36-0.42, p &lt; 0.0001; absolute percent 62.3% to 43.8%). Black patients and women were also less likely to have surgery (p &lt; 0.001). Similar trends by year for primary surgery were observed among each of the subgroups, although patients with colon primary, young adults (age &lt; 50), and patients also undergoing metastatectomy were more likely to undergo primary surgery (p &lt; 0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with later year of diagnosis, with patients diagnosed in 2016 221% more likely to receive chemotherapy than those diagnosed in 2000 (AOR 2.21, 95% CI 2.04 to 2.40, p &lt; 0.0001; 45.5% to 64.0%). Conclusions: From 2000-2016, we observed a sharp decline in the rate of primary surgical resection for patients with metastatic CRC, while use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC, perhaps with stratification by molecular and clinical characteristics, in order to optimize both cancer-specific and symptomatic outcomes.

One-stage resection of primary colorectal cancer and hepatic metastases using the Habib Device: analysis of 40 consecutive cases treated in a Unit of general surgery.

More than 50% of patients with colorectal cancer (CRC) present or develop hepatic metastases (HM). The intraoperative use of the Habib 4X® radio frequency probe device is safe in resetting HM and allows a one-stage resection of both CRC and HM with a similar mortality rate than a two-stage surgical treatment. After an exhaustive residential training at the reference center for hepato-biliary surgery of the Imperial College of London, we treated at our unit of general surgery 40 consecutive patients with CRC and HM with the one-stage resection, using the Habib 4X® intraoperative radiofrequency probe device to reset HM. None of the 40 patients died during the intra-operatory and post-operatory periods, none presented liver failures during the postoperative course nor complication related to the Habib's resection procedure (e.g. bleeding, abscess, bile leak). The amount of intra-operative liver bleeding was minimal. New HM arose in 10 (25%) cases, with a mean disease-free interval of 13 months, but the hepatic tissue close to previous resections remained cancer-free. The 69.7% of patients were disease-free at month 24 of the post-operative follow-up and 5-year rate was about 70%. The data suggest that surgeons well trained at a reference center for hepato-biliary surgery may perform with excellent results the one-stage CRC and HM resection with the Habib 4X® device even in a Unit of general surgery.

Impact on operative outcomes of laparoscopic simultaneous resection of colorectal cancer and synchronous liver metastases.

The efficacy of laparoscopic simultaneous resection of primary colorectal cancer and synchronous colorectal liver metastases (SCRLM) remains unclear. We retrospectively evaluated data from 258 patients who had undergone simultaneous curative resection of the primary tumor and SCRLM from 2006 to 2017. We compared surgical outcomes between open, hybrid (laparoscopic colorectal resection and open hepatectomy), and pure laparoscopic approaches. Surgical outcomes were also evaluated between the open hepatectomy (OH) group (ie, open/hybrid surgery) and the laparoscopic hepatectomy (LH) group (ie, pure laparoscopic surgery) in 141 patients later in the study period (2013-2017), when the clinical indications for laparoscopic hepatectomy were restricted to simple wedge resection and/or left lateral sectionectomy in our center. The pure laparoscopic approach was associated with significantly less intraoperative blood loss and a significantly shorter postoperative hospital stay than the open and hybrid approaches. Late in the study period, operative outcomes in the LH group (n = 37) were more favorable than for the OH group (n = 104) in terms of intraoperative blood loss and postoperative hospital stay. In patients with rectal cancer, however, earlier postoperative recovery in the LH group did not differ significantly from the OH group. Laparoscopic simultaneous resection of SCRLM with the primary tumor by simple hepatectomy is safe and may enhance patients' postoperative recovery, especially in patients with colon cancer.

Influence of primary tumour and patient factors on survival in patients undergoing curative resection and treatment for liver metastases from colorectal cancer.

BackgroundResection of the primary tumour is a prerequisite for cure in patients with colorectal cancer, but hepatic metastasectomy has been used increasingly with curative intent. This national registry study examined prognostic factors for radically treated primary tumours, including the subgroup of patients undergoing liver metastasectomy.MethodsPatients who had radical resection of primary colorectal cancer in 2009–2013 were identified in a population‐based Swedish colorectal registry and cross‐checked in a registry of liver tumours. Data on primary tumour and patient characteristics were extracted and prognostic impact was analysed.ResultsRadical resection was registered in 20 853 patients; in 38·7 per cent of those registered with liver metastases, surgery or ablation was performed. The age‐standardized relative 5‐year survival rate after radical resection of colorectal cancer was 80·9 (95 per cent c.i. 80·2 to 81·6) per cent, and the rate after surgery for colorectal liver metastases was 49·6 (46·0 to 53·2) per cent. Multivariable analysis identified lymph node status, multiple sites of metastasis, high ASA grade and postoperative complications after resection of the primary tumour as strong risk factors after primary resection and following subsequent liver resection or ablation. Age, sex and primary tumour location had no prognostic impact on mortality after liver resection.ConclusionLymph node status and complications have a negative impact on outcome after both primary resection and liver surgery. Older age and female sex were underrepresented in the liver surgical cohort, but these factors did not influence prognosis significantly.

The outcome of primary tumor resection in the unresectable stage IV colorectal cancer patients who received the bevacizumab-containing chemotherapy.

Primary tumor resection (PTR) for unresectable metastatic colorectal cancer (mCRC) patients has been documented to be associated with postoperative hyper-neovascularization and enhanced growth of metastases, which may be prevented by bevacizumab. This study aimed to investigate the survival outcome of PTR in patients who received palliative bevacizumab-containing chemotherapy (BCT).From January 2006 to December 2018, medical records of 240 mCRC patients who received palliative BCT at a single tertiary colorectal cancer center were retrospectively reviewed. Patients were classified into three groups: PTR-a (PTR before BCT, n = 60), PTR-b (PTR during BCT, n = 17), and BCT-only group (n = 163). Resectable mCRCs or recurrent diseases were excluded, and the end-point was overall survival (OS) rate.Three groups had similar age, cell differentiation, location of the primary tumor, and the number of metastatic organs. More than two-thirds of patients who received PTR experienced disease-progressions (PD) during their postoperative chemotherapy-free time (PTR-a vs PTR-b; 66.7% vs 76.5%, P = .170), but OS was not inferior to the BCT-only group (PTR-a vs BCT-only; HR 0.477 [95% CI 0.302–0.754], P = .002/PTR-b vs BCT-only; HR 0.77 [95% CI 0.406–1.462], P = .425). The postoperative chemotherapy-free time was similar between PTR-a and PTR-b (median 32.0 [14–98] days vs 41.0 [18–71] days, P = .142), but non-obstructive indications (perforation, bleeding, pain) were the more frequent in the PTR-b than PTR-a. Young age, the number of BCT, and PTR-a were the independent factors for OS.The efficacy of the PTR for unresectable mCRC has been controversial, but this study demonstrated that PTR should be considered for the unresectable mCRC patients regardless before and during BCT.

Effect of phenotype on outcome in synchronously resected primary colorectal cancer and matched liver metastases.

221 Background: 5-year survival of patients with resectable colorectal liver metastases is 25-40%. Mechanisms of disease progression are heterogenous and do not follow a clearly defined pathway from genotype to phenotype. In stage I-III colorectal cancer (CRC), patients with high tumor stroma exhibit poor prognosis, while those with high immune cell infiltrate do well following resection. We hypothesise that stromally-dense phenotypes lead to T cell exclusion, myeloid cell accumulation and aggressive metastatic progression. Here, we examine relationships between histological tumor phenotype, cellular infiltrate and outcomes in metastatic CRC. Methods: A unique cohort of synchronously resected primary CRC and matched liver metastases (n = 46) were assessed for immune cell infiltration (CD3, CD4, CD8, CD68, CD66b), inflammatory signalling (CXCR2, PDL-1, MMP9) and hypoxia (CAIX) using immunohistochemistry. Tumors were phenotypically subtyped using immune infiltrate (Klintrup-Makinen Grade (KM)), stromal invasion (tumor-stroma percentage (TSP)) and proliferation (Ki67). Results: Phenotypic subtype of primary tumors was predictive of metastatic subtype (rho = 0.522, p = 0.003). Immune phenotypes were associated with good prognosis and stromal phenotypes with poor prognosis (p = 0.004). Infiltration of macrophages and granulocytes associated with poor outcomes (p = 0.018) and increased CXCR2 expression (p = 0.03) at both sites. Increased CXCR2+ cells and macrophages at both sites associated with stromal phenotype (p = 0.02), tumour budding (p = 0.002), low KM grade (p = 0.05) and poor prognosis (p = 0.002). Macrophage and MMP9 levels increased in metastases compared to primary tumour, but no changes were seen in lymphocyte infiltration, CXCR2 and CD66b. Conclusions: Density of immune cell infiltrate, in the primary and metastatic niche, conferred good prognosis. In contrast, stromal, myeloid rich tumors convey poor prognosis. This clinically relevant and histologically efficient process permits segregation of disease and supports further study of relationships in the tumour microenvironment of CRC in the context of chemotherapy to better target therapeutics to individual patients.