Synchronous Liver Metastases Research Articles

Risk factors, prognostic predictors, and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis.

Liver metastasis (LM) remains a major cause of cancer-related death in patients with pancreatic cancer (PC) and is associated with a poor prognosis. Therefore, identifying the risk and prognostic factors in PC patients with LM (PCLM) is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients. However, there are limited data on risk and prognostic factors in PCLM patients. To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms. Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance, Epidemiology, and Results Database. Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode. The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model. The performance of the two nomogram models was evaluated using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and risk subgroup classification. The Kaplan-Meier method with a log-rank test was used for survival analysis. We enrolled 33459 patients with PC in this study. Of them, 11458 (34.2%) patients had LM at initial diagnosis. Age at diagnosis, primary site, lymph node metastasis, pathological type, tumor size, and pathological grade were identified as independent risk factors for LM in patients with PC. Age > 70 years, adenocarcinoma, poor or anaplastic differentiation, lung metastases, no surgery, and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM. The C- index of diagnostic and prognostic nomograms were 0.731 and 0.753, respectively. The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves, calibration plots, and DCA curves. The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation. Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention. External validation is required to confirm these results.

Simultaneous resection of primary tumour and metastases for colorectal cancer with synchronous liver metastases: a single centre experience.

Introduction: Approximately 22% of patients with colorectal cancer present with synchronous metastases. More patients are undergoing resection of liver metastases as surgical strategies and neoadjuvant treatments advance, shifting management from palliation to disease control. Surgical management of colorectal cancer with synchronous liver metastases is traditionally performed separately. Multiple retrospective simultaneous surgery reports deem synchronous resection feasible but outcome data are heterogeneous data and limited. The aim of this study was to analyse the experience of simultaneous resection of the primary tumour and liver metastasis at a UK tertiary centre with attention to surgical, oncological outcomes and survival benefit.

A Case of Cecal Adenocarcinoma with Synchronous Liver Metastasis and BRCA1 Pathological Variant Detected in the Germline as a Secondary Finding ofa Cancer Gene Panel Test

症例は75歳女性で，倦怠感を主訴に精査し，盲腸癌，切除不能多発肝転移，腹膜播種と診断された．コンパニオン遺伝子検査結果ではRAS変異型（KRAS G12V），BRAF V600E野生型，microsatellite stableで，FOLFOX+bevacizumab療法を導入した．がん遺伝子パネル検査を行ったところ，生殖細胞系列にBRCA1病的バリアントが検出され，遺伝性乳癌卵巣癌症候群と診断され，本人および家族に対して遺伝カウンセリングを行った．がん遺伝子パネル検査の普及により，期せずして生殖細胞系列に二次的所見が得られ，遺伝性疾患の診断に繋がる機会は増えると予測される．このことは説明同意文書には必ず記載があるものの，患者側のみならず医療者側も認識に乏しい場合は少なくなく，今一度，患者への十分な説明を肝に銘じ，遺伝カウンセリングの体制を整えることが極めて重要である．

Spatial transcriptomics deconvolves prognosis in colorectal cancer with synchronous liver metastases

Background: Patients demonstrating strong immune responses to primary colorectal cancer (CRC) have a survival benefit following surgery, while those with predominantly stromal microenvironments do poorly. Biomarkers to identify patients with colorectal cancer liver metastases (CRLM) who have good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary CRC and CRLM, and to interrogate the underlying functional biology that drives disease progression.

A Predictive Model for the Early Death of Breast Cancer With Synchronous Liver Metastases: A Population-Based Study.

Breast cancer liver metastasis (BCLM) is a severe condition often resulting in early death. The identification of prognostic factors and the construction of accurate predictive models can guide clinical decision-making. A large sample of data from the Surveillance, Epidemiology, and End Results (SEER) database was analyzed, including 3711 patients diagnosed with de novo BCLM between 2010 and 2015. Predictive models were developed using histograms, and stepwise regression addressed variable collinearity. Internal validation was performed, and results were compared to similar studies. In this study of 3711 BCLM patients, 2571 didn't have early death. Out of the 1164 who died early, 1086 had cancer-specific early death. Prognostic factors for early death, including age, race, tumor size, and lymph node involvement, were identified. A nomogram based on these factors was constructed, accurately predicting early all-cause and cancer-specific death. Valuable insights into the prognosis of BCLM patients were provided, and important prognostic factors for early death were identified. The developed nomogram can assist clinicians in identifying high-risk patients for early death and inform treatment decisions.

Deep learning-based assessment of body composition and liver tumour burden for survival modelling in advanced colorectal cancer.

Personalized therapy planning remains a significant challenge in advanced colorectal cancer care, despite extensive research on prognostic and predictive markers. A strong correlation of sarcopenia or overall body composition and survival has been described. Here, we explore whether automated assessment of body composition and liver metastases from standard of care CT images can add to clinical parameters in personalized survival risk prognostication. We retrospectively analysed clinical imaging data from 85 patients (50.6% female, mean age 58.9 SD 12.2years) with colorectal cancer and synchronous liver metastases. Pretrained deep learning models were used to assess body composition and liver metastasis geometry from abdominal CT images before the initiation of systemic treatment. Abdominal muscle-to-bone ratio (MBR) was calculated by dividing abdominal muscle volume by abdominal bone volume. MBR was compared with body mass index (BMI), abdominal muscle volume, and abdominal muscle volume divided by height squared. Differences in overall survival based on body composition and liver metastasis parameters were compared using Kaplan-Meier survival curves. Results were correlated with clinical and biomarker data to develop a machine learning model for survival risk prognostication. The MBR, unlike abdominal muscle volume or BMI, was significantly associated with overall survival (HR 0.39, 95% CI: 0.19-0.80, P=0.009). The MBR (P=0.022), liver metastasis surface area (P=0.01) and primary tumour sidedness (P=0.007) were independently associated with overall survival in multivariate analysis. Body composition parameters did not correlate with KRAS mutational status or primary tumour sidedness. A prediction model based on MBR, liver metastasis surface area and primary tumour sidedness achieved a concordance index of 0.69. Automated segmentation enables to extract prognostic parameters from routine imaging data for personalized survival modelling in advanced colorectal cancer patients.

Safety and Efficacy of Simultaneous Resection of Gastric Carcinoma and Synchronous Liver Metastasis-A Western Center Experience.

Background and objectives: Gastric cancer (GC) is often diagnosed in the metastatic stage. Palliative systemic therapy is still considered the gold standard, even for patients with resectable oligometastatic disease. The aim of the current study is to assess the potential benefit of up-front gastric and liver resection in patients with synchronous resectable liver-only metastases from GC (LMGC) in a Western population. Materials and Methods: All patients with GC and synchronous LMGC who underwent gastric resection with or without simultaneous resection of LMs between January 1997 and December 2016 were selected from the institutional records. Those with T4b primary tumors or with unresectable or more than three LMs were excluded from the analysis. All patients who underwent emergency surgery for hemorrhagic shock or gastric perforation were also excluded. Results: Out of 28 patients fulfilling the inclusion criteria, 16 underwent simultaneous gastric and liver resection (SR group), while 12 underwent palliative gastric resection (GR group). The median overall survival (OS) of the entire cohort was of 18.81 months, with 1-, 3- and 5-year OS rates of 71.4%, 17.9% and 14.3%, respectively. The 1-, 3- and 5-year OS rates in SR group (75%, 31.3% and 25%, respectively) were significantly higher than those achieved in GR group (66.7%, 0% and 0%, respectively; p = 0.004). Multivariate analysis of the entire cohort revealed that the only independent prognostic factor associated with better OS was liver resection (HR = 3.954, 95% CI: 1.542-10.139; p = 0.004). Conclusions: In a Western cohort, simultaneous resection of GC and LMGC significantly improved OS compared to patients who underwent palliative gastric resection.

Simultaneous Hepatic and Visceral Resection: Preoperative Risk Stratification and Implications on Return to Intended Oncologic Therapy.

Sequence of therapies for synchronous liver metastasis (LM) is complex, with data supporting individualized approaches, although no guiding tools are currently available. We assessed the impact of simultaneous hepatic and visceral resections (SHVR) on textbook outcome (TO) and return to intended oncologic therapy (RIOT), and provide risk-stratification tools to guide individualized decision making and counseling. Patients with synchronous LM undergoing hepatectomy ± SHVR were included (2015-2021). Primary and secondary outcomes were TO and RIOT (days), respectively. Using multivariable modeling, a risk score for TO was developed. Decision tree analysis using recursive partitioning was performed for hierarchical risk stratification. The associations between SHVR, TO, and RIOT were examined. Among 533 patients identified, 124 underwent SHVR. TO overall was 71.7%; 79.2% in the non-SHVR group and 46.8% in the SHVR group (p<0.001). SHVR was the strongest predictor of non-TO (right colon/small bowel: odds ratio [OR] 4.63, 95% confidence interval [CI] 2.65-8.08; left colon/rectum: OR 6.09, 95% CI 2.59-14.3; stomach/pancreas: OR 6.69, 95% CI 1.46-30.7; multivisceral: OR 10.9, 95% CI 3.03-39.5). A composite score was developed yielding three risk strata for TO (score 0-2: 89% vs. score 3-5: 67% vs. score ≥ 6: 37%; p<0.001). Decision tree analysis was congruent, identifying SHVR as the most important determinant of TO. In patients with colorectal LM, SHVR was associated with delayed time to RIOT (p=0.004); the risk-stratification tool for TO was equally predictive of RIOT (p<0.01). SHVR is associated with reduced likelihood of TO and in turn delayed RIOT. As SHVR is increasingly performed in order to consolidate cancer care, patient selection considering these different outcomes is critical.

Natural History of Stage IV Pancreatic Cancer. Identifying Survival Benchmarks for Curative-intent Resection in Patients With Synchronous Liver-only Metastases.

To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients. Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups. We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan-Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis. We identified 241 patients. Median OS was 7 months (95% CI, 5-9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17-39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR). The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.

Health-Related Quality of Life Following Simultaneous Resection for Synchronous Colorectal Cancer Liver Metastases.

Up to 25% of colorectal cancer patients present with synchronous liver metastases that can be treated with two operations or a single 'simultaneous' operation. Morbidity and mortality appear similar between approaches, however changes in health-related quality-of-life following simultaneous resection are not well reported. A prospective, feasibility trial for simultaneous resection of synchronous colorectal liver metastases was conducted. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 at baseline (preoperatively), and 4 and 12weeks postoperatively. Week 4 and 12 scores were compared with baseline using t-tests. Minimally important clinical differences were considered as a 10-point difference from baseline. C30 and QLQ-LMC21 were completed at baseline, 4weeks, and 12weeks by 39 (95%), 35 (85%) and 34 (83%) patients, and 39 (95%), 33 (80%) and 33 (80%) patients, respectively; 79% and 75% had at least one MICD according to QLQ-C30 at 4 and 12 weeks. At 4 weeks, physical functioning (mean difference (MD) - 11.9%, p = 0.002), role functioning (MD - 23.6, p = 0.007), and pain (MD + 19.7, p = 0.017) had significant worsening from baseline. At 12 weeks postoperatively, role functioning (MD - 19.7, p = 0.011) and fatigue (MD + 14.3, p = 0.03) were the only domains that remained significantly worse. By 12 weeks, pain and physical functioning had returned to baseline. There were no major demographic differences among those with and without an MICD at 12 weeks. Simultaneous resection of colorectal liver metastases led to clinically significant worsening fatigue and role functioning that persisted at 12weeks post-surgery.

Single-cell transcriptome analysis of tumor immune microenvironment characteristics in colorectal cancer liver metastasis.

Liver metastasis is the leading cause of death in colorectal cancer (CRC) patients, and the precise mechanisms remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the cellular and molecular heterogeneity between CRC primary lesion and corresponding liver metastasis, and to clarify the characteristics of the tumor microenvironment (TME) in synchronous liver metastasis of CRC. A case of microsatellite stable (MSS) sigmoid carcinoma with synchronous liver metastasis was selected, and tissues from the primary tumor and the liver metastasis were collected for scRNA-seq. The EdgeR package software was used to identify the differentially expressed genes between cells. Gene Set Enrichment Analysis (GSEA) was performed and the clusterProfiler R package was used for Gene Ontology (GO) enrichment analysis. The SCENIC and CellphoneDB packages were used to reconstruct the transcriptional regulatory networks and to analyze the intercellular interaction network, respectively. Compared to the primary tumor, the proportion of myeloid cells in the metastatic tumor was significantly increased, while B cells and plasma cells were decreased. In the metastatic tumor, the myeloid-derived suppressor cell (MDSC) characteristic gene, mannose receptor C-type 1 (MRC1) and tumor associated macrophage 2 (TAM2)-related gene, were highly expressed. Furthermore, angiogenesis, oxidative phosphorylation, and endothelial mesenchymal transition (EMT) of myeloid cells were also significantly enhanced. There were less myeloid cells in primary tumors, and these were mainly monocytes and TAM1; while the number of TAM2 was significantly upregulated in the metastatic samples. In liver metastasis, the T cell population was exhausted, and this was accompanied by a significant increase in the number of CD4+ T cells and a decrease in the number of CD8+ T cells. Furthermore, some immune checkpoint molecules were highly expressed. Interactions between myeloid cells and other cell populations appeared to be strong. The TME of CRC liver metastasis is significantly immunosuppressed. Interactions between myeloid cells and other cell populations in the TME contribute to the establishment of a pro-metastatic niche that promotes colonization and growth of CRC cells in the liver. TAMs may be a potential immunotherapeutic target for MSS CRC.

Disparities in treatment and survival for patients with isolated colorectal liver metastases

BackgroundSurgical resection improves survival for patients with isolated colorectal liver metastasis. National studies on the disparities related to this topic are limited; therefore, we investigated factors that affect surgical treatment and survival. MethodsWe queried the National Cancer Database (2010–2017) for patients with isolated synchronous colorectal liver metastasis. Multivariable logistic regression and Cox proportional hazard regressions were used to identify factors associated with surgical resection, treatment at high-volume facilities, and overall survival. ResultsOf 34,050 patients with isolated colorectal liver metastasis, surgical resection (n = 7,810; 23.0%) was more likely among patients who were of high socioeconomic status (odds ratio = 1.16; 95% confidence interval, 1.04–1.31), traveled long distance for treatment (odds ratio = 1.48; 95% confidence interval, 1.31–1.66), and were treated at high-volume facilities (odds ratio = 4.86; 95% confidence interval, 14.45–5.30). Black patients were less likely to undergo resection (odds ratio = 0.75; 95% confidence interval, 0.69–0.82). Treatment at high-volume facility was more common among patients who were Black (odds ratio = 1.14; 95% confidence interval, 1.07–1.21), were of high socioeconomic status (socioeconomic status index 7: odds ratio = 1.21; 95% confidence interval, 1.11–1.31), and traveled long distance (odds ratio = 4.03; 95% confidence interval, 3.63–4.48) and less likely for nonmetropolitan residents and those of low socioeconomic status (P < .05). Patients of high socioeconomic status and those who traveled long distance, were treated at high-volume facilities, underwent surgical resection, and received perioperative chemotherapy had an associated survival advantage (P < .05 for all), whereas Black race was associated with poorer overall survival (P < .05). ConclusionNonmedical patient factors, such as race, socioeconomic status, and geography, are associated with treatment and survival for isolated colorectal liver metastases. Disparities persist after adjusting for surgical resection and treatment facility. These barriers must be addressed to improve care for vulnerable cancer patients.

Oncological outcomes of neoadjuvant chemotherapy in patients with resectable synchronous colorectal liver metastasis: A result from a propensity score matching study.

The efficacy and safety of neoadjuvant chemotherapy (NAC) in treating resectable synchronous colorectal liver metastases (CRLM) remain controversial. Data from CRLM patients who underwent simultaneous liver resection between January 2015 and December 2019 were collected from the Surveillance, Epidemiology, and End Results (SEER) database (SEER cohort, n=305) and a single Chinese Cancer Center (NCC cohort, n=268). Using a 1:2 ratio of propensity score matching (PSM), the prognostic impact of NAC for patients who underwent NAC before surgical treatment and patients who underwent surgical treatment alone was evaluated. After PSM, there was no significant difference in overall survival (OS) between patients receiving NAC prior to CRLM resection and those undergoing surgery only, in both the NCC and SEER cohorts (each P > 0.05). Age was an independent predictor of OS only in the SEER cohort (P = 0.040), while the pN stage was an independent predictor for OS only in the NCC cohort (P = 0.002). Furthermore, Disease-free survival (DFS) was comparable between the two groups in the NCC cohort. In a subgroup analysis, the DFS and OS in the NAC- group were significantly worse than those in the NAC+ group for patients with more than two liver metastases in the NCC cohort (P < 0.05 for both). NAC did not have a significant prognostic impact in patients with resectable synchronous CRLM. However, patients with more than two liver metastases could be good candidates for receiving NAC.

Neoadjuvant Versus Adjuvant Chemotherapy for Resectable Metastatic Colon Cancer in Non-academic and Academic Programs.

Overall survival advantage of chemotherapy before versus after metastasectomy of liver or lung lesion is not clear for colon cancer with synchronous liver or lung metastasis. Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver or lung at diagnosis were identified between 2010 and 2015 through the National Cancer Database (NCDB). Patients were categorized into 2 cohorts: pre-operative/peri-operative chemotherapy (neoadjuvant -[NAC]) or post-operative chemotherapy (adjuvant [AC]). Survivals and factors associated with were compared between the 2 groups. A total of 3038 patients with colon cancer with liver or lung metastases were identified. The percentage of patients receiving NAC had steadily increased from 12.29% to 28.31%, mostly in academic programs. On multivariate analysis, patients who received NAC had an overall survival advantage in the non-academic setting whereas no advantage is seen in the patients treated in the academic settings. The median overall survival for patients receiving NAC and AC was 47.24 months and 38.08 months, respectively. Factors associated with overall survival advantage in NAC patients treated in non-academic programs included age 20-49 years, CEA value of >30, right-sided colon primary, liver metastasis, and clear resection margins. Metastatic colon cancer with single organ liver or lung lesions benefits from neoadjuvant chemotherapy, especially in -non-academic settings. The overall survival advantage in this setting has not been shown before.

Long-term outcomes of staged liver resection for synchronous liver metastases from colorectal cancer and the clinical impact of early recurrence: A single-center retrospective cohort study.

This study was undertaken to evaluate the long-term outcomes of staged liver resection for synchronous liver metastases (SLM) from colorectal cancer (CRC), and to elucidate the prognostic impact and predictors of early recurrence (ER), which was defined as recurrence within 6 mo. Patients with SLM from CRC, except for initially unresectable SLM, from January 2013 to December 2020 were included. First, overall survival (OS) and relapse-free survival (RFS) after staged liver resection were evaluated. Second, eligible patients were classified as follows: patients who were unresectable after resection of CRC (UR), patients with ER, and patients without ER (non-ER), and their OS after resection of CRC were compared. In addition, risk factors for ER were identified. The 3-y OS and RFS rates after resection of SLM were 78.8% and 30.8%, respectively. Next, the eligible patients were classified as follows: ER (N=24), non-ER (N=56), and UR (N=24). The non-ER group had a significantly better OS than the ER (3-y OS: 89.7% vs 48.0%, P=.001) and UR (3-y OS: 89.7% vs 61.6%, P < .001) groups, while there was no significant difference between the ER and UR groups in OS (3-y OS: 48.0% vs 61.6%, P=.638). Increasing carcinoembryonic antigen (CEA) before and after resection of CRC was identified as an independent risk factor for ER. Staged liver resection for SLM from CRC was feasible and useful for oncological evaluation, as changes in CEA could predict ER, which was associated with a poor prognosis.

Practical Implications of KRAS Mutation Status and Sidedness of Primary Tumour in Patients with Colorectal Cancer and Synchronous Liver Metastases: A Subset Analysis of the CoSMIC Study.

Simple SummaryPatients presenting with liver metastases at the time of diagnosis of their colorectal cancer (termed ‘synchronous disease’) have a worse outcome than those whose disease is limited to the primary bowel tumour. There is evidence to show that patients with tumours on the right side of the colon have worse survival. Furthermore, mutations in the KRAS gene have also been shown to adversely affect outcome. This study explores the association between the side of the primary colorectal tumour in patients with synchronous disease and mutations in the KRAS gene on survival. We analyse a specific cohort of patients from the previously published CoSMIC study who presented with colorectal cancer and synchronous liver metastases and who had their colorectal tumour analysed for KRAS mutations. We find that for this cohort, neither mutations in the KRAS gene nor the side of the colon tumour influenced survival.Patients with colorectal cancer presenting with synchronous liver metastases have less favourable outcomes than those with primary-only disease. There is evidence of different genetic mutational signatures according to the sidedness of the primary tumour. KRAS mutations are key driver mutations in colorectal cancer progression. This post hoc analysis of the previously reported CoSMIC inception cohort explores the association between primary tumour sidedness and KRAS mutational status on the outcome of patients with colorectal cancer and synchronous liver metastases. Patients diagnosed with synchronous disease were recruited between April 2014 and March 2017 and, after exclusions, 83 patients undergoing colorectal primary KRAS mutation testing constituted the final study population. Data were collected prospectively on demographic profiles, treatment, and outcomes. Twenty-one patients (25%) had right-sided tumours and 62 (75%) had left-sided tumours, with 46 (55%) and 37 (45%) exhibiting wildtype and mutated KRAS, respectively. There was no difference in distribution of liver metastases by KRAS status (unilobar vs. bi-lobar; p = 0.58; Fisher’s Exact test) and no difference in 5-year survival according to KRAS mutation status (Log-rank test, p = 0.82) or tumour sidedness (p = 0.16). In summary, in this cohort of patients with colorectal cancer and synchronous liver metastases, neither KRAS mutation status nor tumour sidedness influenced survival.

Simultaneous resection of synchronous colorectal liver metastasis: Feasibility and development of a prediction model.

Timing of resection for synchronous colorectal liver metastasis (CRLM) has been debated for decades. The aim of the present study was to assess the feasibility of simultaneous resection of CRLM in terms of major complications and develop a prediction model for safe resections. A retrospective single-center study of synchronous, resectable CRLM, operated between 2013 and 2021 was conducted. Upper limit of 95% confidence interval (CI) of major complications (≥ grade IIIA) was set at 40% as the safety threshold. Logistic regression was used to determine predictors of morbidity. Prediction model was internally validated by bootstrap estimates, Harrell's C-index, and correlation of predicted and observed estimates. Ninety-two patients were operated. Of them, 41.3% had rectal cancers. Major hepatectomy (≥ 4 segments) was performed for 25 patients (27.2%). Major complications occurred in 20 patients (21.7%, 95% CI: 13.8%-31.5%). Predictors of complications were the presence of comorbidities and major hepatectomy (area under the ROC curve: 0.692). Unacceptable level of morbidity (≥ 40%) was encountered in patients with comorbidities who underwent major hepatectomy. Simultaneous bowel and CRLM resection appear to be safe. However, caution should be exercised when combining major liver resections with bowel resection in patients with comorbid conditions.

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents (64Cu-DOTATATE or 68Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.

Disparities in Care Access to Liver-Directed Therapy Among Medicare Beneficiaries with Colorectal Cancer Liver Metastasis.

BackgroundLiver-directed therapies (LDT) are important components of the multidisciplinary care of patients with colorectal cancer liver metastases (CRCLM) that contribute to improved long-term outcomes. Factors associated with receipt of LDT are poorly understood.Patients and MethodsPatients > 65 years old diagnosed with CRCLM were identified within the Medicare Standard Analytic File (2013–2017). Patients with extrahepatic metastatic disease were excluded. Mixed-effects analyses were used to assess patient factors associated with the primary outcome of LDT, defined as hepatectomy, ablation, and/or hepatic artery infusion chemotherapy (HAIC), as well as the secondary outcome of hepatectomy.ResultsAmong 23,484 patients with isolated CRCLM, only 2004 (8.5%) received LDT, although resectability status could not be determined for the entire cohort. Among patients who received LDT, 61.7% underwent hepatectomy alone, 28.1% received ablation alone, 8.5% underwent hepatectomy and ablation, and 1.8% received HAIC either alone (0.8%) or in combination with hepatectomy and/or ablation (0.9%). Patient factors independently associated with lower odds of LDT included older age, female sex, Black race, greater comorbidity burden, higher social vulnerability index, primary rectal cancer, synchronous liver metastasis, and further distance from a high-volume liver surgery center (p < 0.05). Results were similar for receipt of hepatectomy.ConclusionsDespite the well-accepted role of LDT for CRCLM, only a small proportion of Medicare beneficiaries with CRCLM receive LDT. Increasing access to specialized centers with expertise in LDT, particularly for Black patients, female patients, and those with higher levels of social vulnerability or long travel distances, may improve outcomes for patients with CRCLM.

Association of Simultaneous vs Delayed Resection of Liver Metastasis With Complications and Survival Among Adults With Colorectal Cancer

Simultaneous or delayed resection of synchronous liver metastasis (SLM) with primary colorectal cancer (CRC) remains a controversial topic. To investigate the outcomes of simultaneous vs delayed resection in patients with resectable SLM. This comparative effectiveness research study included 1569 patients with resectable SLM who underwent curative-intent liver resection at 3 independent centers in China between January 1, 2000, to December 31, 2019. A 1:1 propensity score matching was performed. Follow-up was completed on August 31, 2021, and the data were analyzed from April 1 to 30, 2022. Primary outcome was the percentage of patients with at least 1 major complication within 60 days after surgery. Secondary outcomes were intraoperative and postoperative complications, overall survival (OS), and cancer-specific survival (CSS) rates. Among the 1569 patients included, 1057 (67.4%) underwent delayed resection (719 men [68.0%] with a mean [SD] age of 57.4 [11.2] years), and 512 patients (310 men [60.5%] with a mean [SD] age of 57.1 [10.5] years) underwent simultaneous resection. Matching yielded 495 pairs of patients underwent simultaneous resection. The percentage of major perioperative complications did not differ between the simultaneous and delayed resection groups (34.1% vs 30.0%; P = .89). The OS rates were 65.2% at 3 years, 47.1% at 5 years, and 38.0% at 8 years for the delayed resection group and 78.0% at 3 years, 65.4% at 5 years, and 63.1% at 8 years for the simultaneous resection group (hazard ratio [HR], 1.42; 95% CI, 1.10-1.85, P = .003). The CSS rates were 68.3% at 3 years, 48.5% at 5 years, and 37.1% at 8 years for the delayed resection group and 79.2% at 3 years, 67.2% at 5 years, and 65.9% at 8 years for the simultaneous resection group (HR, 1.45; 95% CI, 1.14-1.98; P = .004). On subgroup analysis comparing the 2 strategies according to the KRAS sequence variation status, the OS rates (HR, 1.61; 95% CI, 1.45-2.18; P < .001) and CSS rates (HR, 1.62; 95 CI, 1.40-1.87; P = .003]) in the simultaneous resection group were significantly better than those in the delayed resection group in patients with KRAS wild-type tumors. Results of this study suggest that complication rates did not differ when CRC and SLM were resected simultaneously and that the survival benefits of simultaneous resection were restricted to patients with KRAS wild-type tumors. Integrating molecular features into the treatment decision is a basis for accurate, individualized treatments.