Metachronous Liver Metastases Research Articles

Prognostic assessment of T-cells in primary colorectal cancer and paired synchronous or metachronous liver metastasis.

Prognostic value of T-cells between primary colorectal cancer (pCRC) and its paired synchronous and metachronous liver metastasis (LM) is underinvestigated and is the subject of the present study. We enrolled into this retrospective cohort study patients, who underwent resection of both pCRC and synchronous LM (N = 55) or metachronous LM (N = 44). After immunohistochemical staining for CD3+, CD8+, and CD45R0+ whole slides were scanned and T-cell densities were quantified using QuPath software in tumor center (TC), inner margin (IM), outer margin (OM), and peritumor zone (PT) of pCRC and LM. High densities of CD8+ T-cells in TC, OM and PT of synchronous LM were associated with longer disease-free survival (DFS). Greater densities of CD3+ T-cells in IM and PT and CD8+ T-cells in IM, OM and PT in synchronous LM over pCRC were associated with longer DFS. Greater densities of CD8+ T-cells in the TC and IM and CD3+ T-cells in the IM of pCRC were found in the metachronous over synchronous group. The first novel finding demonstrated that high density of CD8+ T cells in synchronous LM were associated with favorable outcome. The second finding of high CD8+ cell density in pCRC in metachronous over synchronous CRC may provide a mechanistic basis for the delay of metastatic spread. Both findings could be applied clinically with own reference values.

CT feature of irregular extensive ulceration as a predictor of liver metastasis in gastric gastrointestinal stromal tumours.

This study aimed to investigate whether the computed tomography (CT) finding of irregular extensive ulceration (IEU) can serve as a predictor of liver metastasis (LIM) in patients with gastric gastrointestinal stromal tumours (GISTs). This study retrospectively collected clinical and imaging data from 286 patients diagnosed with low-, intermediate-, or high-risk gastric GISTs, or primary lesions with LIM from three medical institutions. The patients were categorised into non-LIM and LIM groups according to whether they had synchronous or metachronous LIM. Multivariate logistic regression analyses were performed to identify significant predictors of LIM. Additionally, receiver operating characteristic (ROC) curve, subgroup, and pathologic-radiologic correlation analyses were conducted. A total of 124 patients were ultimately enroled. There were significant differences in sex, site, growth pattern, size, shape, ulceration and Ki-67 expression between LIM and non-LIM groups. ROC curve analysis demonstrated that IEU had the highest area under the curve for predicting LIM (AUC = 0.842; 95% CI: 0.760-0.924; p < 0.001). Multivariate analysis indicated that IEU was the most significant independent predictor of high LIM risk (OR = 88.62; 95% CI: 2.80-2803.54; p = 0.011). Subgroup analysis showed that IEU was more frequently associated with male sex, age ≤ 55 years, proximal sites, irregular shapes, mixed growth patterns, and a high Ki-67 expression. The CT feature of IEU serves as an independent predictor of LIM in gastric GISTs and is strongly associated with high Ki-67 expression. Question Accurate assessment of LIM risk in patients with gastric GISTs is crucial, yet current non-invasive predictors remain inadequate. Findings IEU on CT is an independent predictor of LIM, with high diagnostic accuracy and a significant association with elevated Ki-67 expression. Clinical relevance IEU on CT scans enables non-invasive risk stratification for LIM in gastric GISTs. Our study refined the assessment of ulceration types, highlighting significant heterogeneity, which may guide personalised treatment strategies.

New definition of borderline resectable colorectal liver metastasis based on prognostic outcomes.

Although surgical resection is the curative treatment for colorectal liver metastases (CRLM), the efficacy of neoadjuvant chemotherapy (NAC) has been discussed due to recent remarkable advances in chemotherapy. The definition of borderline resectable (BR) is most important, where neoadjuvant chemotherapy should be administered. This study aimed to examine a new definition of BR CRLM based on the results of the treatment outcomes. This study included 127 patients who underwent liver resection for CRLM after exclusion of conversion cases between April 2010 and December 2023. Upfront resection was performed for synchronous and single liver metastasis or metachronous liver metastases. NAC was administered for multiple synchronous liver metastases. In order to find a new definition of BR, we examined the prognostic factors obtained from the treatment outcomes. CA19-9 level > 37.0 was the only prognostic factor in the upfront group [hazard ratio (HR) 2.386, 95% CI, 1.583-4.769; p = 0.049]. in the NAC group, a maximum tumor diameter ˃3 cm (HR 2.248, 95% CI 1.038-4,867, p = 0.040), CA19-9 level > 37.0 (HR 2.239, 95% CI 1.044-4.800, p = 0.038), and a right-sided primary tumor in the colon (HR 2.770, 95% CI 1.284-5.988, p = 0.009) were identified as significant prognostic factors. In cases of CRLM, patients with CA19-9 levels > 37.0, or CA19-9 level with < 37.0 but with a primary tumor in the right colon or a maximum tumor diameter of > 3cm can be defined as BR CRLM and should be treated with NAC.

Development and validation of a TRIM27-based nomogram for predicting metachronous liver metastasis and prognosis in postoperative colorectal cancer patients

BackgroundColorectal cancer ranks among the most prevalent malignancies globally. Accurate prediction of metachronous liver metastasis is crucial for optimizing postoperative management. Tripartite motif-containing protein 27 (TRIM27), an E3 ubiquitin ligase, is implicated in diverse cellular functions and tumorigenesis.MethodsThis study aimed to develop and validate a TRIM27-based nomogram for prognostication in colorectal cancer patients. Transcriptome sequencing of five paired tumor and normal tissue samples identified TRIM27 as a potential prognostic biomarker. Immunohistochemistry was employed to assess TRIM27 expression in colorectal cancer cohorts from two institutions.ResultsTRIM27 expression correlated significantly with both the prognosis of colorectal cancer patients and the occurrence of metachronous liver metastasis. A nomogram incorporating TRIM27 and clinical factors was constructed and demonstrated robust predictive accuracy in an independent validation cohort.ConclusionThe TRIM27-based nomogram is a valuable prognostic tool for predicting prognosis and metachronous liver metastasis in colorectal cancer patients, aiding in personalized treatment decisions.

An actinomycosis infection resembling peritoneal dissemination of rectal cancer: a case report

BackgroundActinomycosis is a suppurative and granulomatous inflammation commonly caused by Actinomyces israelii. Due to its rarity and the paucity of characteristic clinical features, diagnosis of intra-abdominal actinomycosis is challenging, especially when the patient has a treatment history of abdominal cancer.Case presentationThe patient is a 72-year-old man who has a history of multiple abdominal surgeries for rectal cancer, including low anterior resection for primary rectal cancer, partial hepatic resection for metachronous liver metastasis, and Hartmann surgery for local recurrence. The patient has also undergone parastomal hernia repair using the Sugarbaker method. One year after hernia repair, computed tomography (CT) identified a mass lesion between the abdominal wall and the mesh, suggesting the possibility of peritoneal recurrence of rectal cancer. The accumulation of fluorodeoxyglucose (FDG) was evident via positron emission tomography-CT (PET-CT), while tumor marker levels were within the normal range. On laparotomy, the small intestine, abdominal wall, mesh, colon, and stoma were observed to be associated with the mass lesion, and en bloc resection was carried out. However, postoperative histopathological examination revealed an actinomyces infection without any cancerous cells.ConclusionsThis case highlights the challenges faced by surgeons regarding preoperative diagnosis of actinomycosis, especially when it occurs after the resection of abdominal cancer. Also, this case reminds us of the importance of a histopathological examination for abdominal masses or nodules before starting chemotherapy.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Right hepatectomy in absence of the left portal vein using the porto-rex shunt procedure

Abstract Objectives Exact knowledge of the portal vein (PV) anatomy is essential for any hepatobiliary procedure. Absence of the portal bifurcation with the complete blood flow to the left lobe coming from the right portal vein (RPV) is an extremely rare anatomical variation. Case presentation In this situation, a solitary metachronous colorectal liver metastasis with suspected infiltration of the RPV and the right bile duct was detected in a 51-year-old male patient. Neither percutaneous ablation nor stereotactic radiotherapy were considered indicated due to the close proximity to the central structures. Hence, a surgical two-step procedure was scheduled. First, a porto-rex shunt with an 8 mm PTFE graft to maintain the portal blood flow to the left lobe was performed. In addition, the RPV was ligated during the same procedure. After recovery, the procedure was completed with a right hepatectomy. The final pathological report confirmed invasion of the right bile duct and the RPV and resection margins were tumor-free. Conclusion This case shows that careful preoperative assessment of vascular anatomy is critical. The use of the porto-rex shunt allowed a potentially curative resection in an otherwise irresectable situation.

Construction of a nomogram model based on biomarkers for liver metastasis in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) with liver metastasis have a poor prognosis, and there are no reliable biomarkers for predicting disease progression. Currently, no recognized and reliable prediction model exists to anticipate liver metastasis in NSCLC, nor have the risk factors influencing its onset time been thoroughly explored. This study conducted a retrospective analysis of 434 NSCLC patients from two hospitals to assess the association between the risk and timing of liver metastasis, as well as several variables. The patients were divided into two groups: those without liver metastasis and those with liver metastasis. We constructed a nomogram model for predicting liver metastasis in NSCLC, incorporating elements such as T stage, N stage, M stage, lack of past radical lung cancer surgery, and programmed death ligand 1 (PD-L1) levels. Furthermore, NSCLC patients with wild-type EGFR, no prior therapy with tyrosine kinase inhibitors (TKIs), and no prior radical lung cancer surgery showed an elevated risk of early liver metastasis. In conclusion, the nomogram model developed in this study has the potential to become a simple, intuitive, and customizable clinical tool for assessing the risk of liver metastasis in NSCLC patients following validation. Furthermore, it provides a framework for investigating the timing of metachronous liver metastasis.

SLC14A1 and TGF-β signaling: a feedback loop driving EMT and colorectal cancer metachronous liver metastasis

BackgroundColorectal cancer (CRC) metachronous liver metastasis is a significant clinical challenge, largely attributable to the late detection and the intricate molecular mechanisms that remain poorly understood. This study aims to elucidate the role of Solute Carrier Family 14 Member 1 (SLC14A1) in the pathogenesis and progression of CRC metachronous liver metastasis.MethodsWe conducted a comprehensive analysis of CRC patient data from The Cancer Genome Atlas and GSE40967 databases, focusing on the differential expression of genes associated with non-metachronous liver metastasis and metachronous liver metastasis. Functional assays, both in vitro and in vivo, were performed to assess the biological impact of SLC14A1 modulation in CRC cells. Gene set enrichment analysis, molecular assays and immunohistochemical analyses on clinical specimens were employed to unravel the underlying mechanisms through which SLC14A1 exerts its effects.ResultsSLC14A1 was identified as a differentially expressed gene, with its overexpression significantly correlating with poor relapse-free and overall survival. Mechanistically, elevated SLC14A1 levels enhanced CRC cell invasiveness and migratory abilities, corroborated by upregulated TGF-β/Smad signaling and Epithelial-Mesenchymal Transition. SLC14A1 interacted with TβRII and stabilized TβRII protein, impeding its Smurf1-mediated K48-linked ubiquitination and degradation, amplifying TGF-β/Smad signaling. Furthermore, TGF-β1 reciprocally elevated SLC14A1 mRNA expression, with Snail identified as a transcriptional regulator, binding downstream of SLC14A1’s transcription start site, establishing a positive feedback loop. Clinically, SLC14A1, phosphorylated Smad2, and Snail were markedly upregulated in CRC patients with metachronous liver metastasis, underscoring their potential as prognostic markers.ConclusionsOur findings unveil SLC14A1 as a critical regulator in CRC metachronous liver metastasis, providing novel insights into the molecular crosstalk between SLC14A1 and TGF-β/Smad signaling. These discoveries not only enhance our understanding of CRC metachronous liver metastasis pathogenesis, but also highlight SLC14A1 as a promising target for therapeutic intervention and predictive marker.

Temporal and spatial heterogeneity of HER2 status in metastatic colorectal cancer

BackgroundHER2-targeted therapies have recently emerged as an option in the management of metastatic colorectal cancer (mCRC) overexpressing HER2. However, data regarding HER2 status in primary CRC and its corresponding liver metastases are limited, potentially influencing clinical decisions. Therefore, the aim of this study was to compare the HER2 status in primary CRC and paired liver metastases.MethodsPatients with mCRC who were operated from their primary colorectal cancer and their corresponding synchronous or metachronous liver metastases, in the digestive surgery department of Besançon University Hospital, between April 1999 and October 2021, were included. Tissue microarrays were constructed from matched primary CRC and liver metastastic tissue samples. HER2 status was assessed by immunohistochemistry and in situ hybridization according to Valtorta’s criteria.ResultsA series of 108 paired primary CRC and liver metastases, including a series of multiple liver metastases originating from the same patients (n = 24), were assessed. Among the primary CRC, 89 (82.4%), 17 (15.8%) and 2 (1.8%) cases were scored 0, 1 + and 2 + respectively. In liver metastases, 99 (91.7%), 7 (6.5%) and 2 (1.8%) were scored 0, 1 + and 2, respectively. Overall, there was a 19% discrepancy rate in HER2 status between primary CRC and metastases, which increased to 21% in cases with multiple synchronous or metachronous liver metastases in a given patient. No significant difference was found between metachronous and synchronous metastases regarding the HER2 status (p = 0.237).ConclusionsOur study highlights the temporal and spatial heterogeneity of HER2 status between primary CRC and corresponding liver metastases. These findings raise the question of a sequential evaluation of the HER2 status during disease progression, to provide the most suitable treatment strategy.

Case Report: Metachronous intussusception: A complex case report of small intestinal adenocarcinoma

Small intestinal adenocarcinomas, comprising less than 5% of digestive cancers, present diagnostic and therapeutic intricacies often overshadowed by more common digestive malignancies. This report highlights the unique metachronous characteristic of the case, emphasizing the presence of intussusception, to contribute valuable knowledge and refine medical approaches for optimizing outcomes in these rare and complex scenarios. A 73-year-old male, previously operated for right colon adenocarcinoma, developed metachronous liver metastasis a year later, successfully treated. Presenting with acute intestinal obstruction, imaging confirmed mechanical obstruction, prompting small intestine resection and stoma creation. The postoperative phase, characterized by meticulous care, ensures ongoing close oncological follow-up for this complex medical journey, with the added complication of intussusception. Amid the rarity of small intestinal adenocarcinomas in digestive cancers, our unique case sheds light on the challenges in diagnosis and treatment, particularly highlighting the presence of intussusception. The distinctive approach of small intestine resection and stoma creation underscores ongoing debates on adjuvant chemotherapy, reflecting an evolving management landscape. This underscores the crucial role of continuous research and multidisciplinary strategies in optimizing outcomes for patients facing this uncommon malignancy complicated by intussusception. This report provides valuable insights into the complexities of diagnosing and managing small intestinal adenocarcinomas, particularly when complicated by intussusception. As we navigate this nuanced medical terrain, continuous research and multidisciplinary approaches remain pivotal for refining our understanding and optimizing outcomes in small intestinal adenocarcinomas.

Abstract 5528: Adaptive immune cells in colorectal cancer between normal mucosa, primary tumor and liver metastasis

Abstract Introduction: We aimed to assess the role of local adaptive immunity in the metastatic process by comparing densities of adaptive immune cells between normal colorectal mucosa (NM), primary colorectal cancer (pCRC) and liver metastases (LM) in patients with synchronous and metachronous disease. Patients and Methods: We enrolled patients, who underwent resection of pCRC and LM in Pilsen University Hospital between 1999 and 2022. 56 patients presented with LM (stage IV, synchronous) and 43 patients (stage II/III) developed LM later (metachronous). After immunohistochemical staining and whole slide scanning densities of CD3+ and CD8+ T cells and CD20+ B cells were quantified in NM, pCRC and LM using QuPath software. In pCRC and LM cell densities were measured in tumor center (TC), inner margin (IM), outer margin (OM) and peritumor (PT) region. IM and OM were defined as 500 µm on each side of the invasive tumor border. Results: For all examined cells in both groups we found smaller densities in TC of pCRC and LM compared to NM (Table). In pCRC of synchronous group compared to LM densities of all cells were smaller in IM and OM and densities of CD3+ and CD8+ cells were smaller in PT region. In pCRC of metachronous group compared to LM densities of all cells were greater in TC, densities of CD3+ were smaller in OM and PT region, whereas densities of CD20+ cells were smaller only in OM. Compared to metachronous group patients with synchronous metastases had smaller densities of CD3+ T cells in IM and CD8+ T cells in TC and IM of pCRC. Conclusion: Development of pCRC is accompanied by decreased densities of T and B cells in TC compared to NM, which further decrease in metachronous LM. Lower densities of T and B cells in IM and OM and T cells in PT region of pCRC compared to LM is a hallmark of synchronous group. TC of pCRC harbors larger numbers of T and B cells compared to LM in metachronous group. Low numbers of CD3+ and CD8+ T cells in IM and CD8+ T cells in TC of primary CRC may contribute to development of synchronous metastases. Densities of CD3+, CD8+ and CD20+ cells per mm2 of the tissue (median) Patients witn liver metastases Synchronous Metachronous NM pCRC LM NM pCRC LM CD3 NM 1014 1042 CD3 TC 313p&amp;lt;0.05 to NM 249p&amp;lt;0.05 to NM 338p&amp;lt;0.05 to NM 199p&amp;lt;0.05 to NM and pCRC CD3 IM 252 431p&amp;lt;0.05 to pCRC 393p&amp;lt;0.05 to pCRC in synchronous group 483 CD3 OM 521 1437p&amp;lt;0.05 to pCRC 649 1953p&amp;lt;0.05 to pCRC CD3 PT 479 873p&amp;lt;0.05 to pCRC 447 987p&amp;lt;0.05 to pCRC CD8 NM 319 390 CD8 TC 58p&amp;lt;0.05 to NM 52p&amp;lt;0.05 to NM 102p&amp;lt;0.05 to NM and to pCRC in synchronous group 52p&amp;lt;0.05 to NM and pCRC CD8 IM 65 96p&amp;lt;0.05 to pCRC 102p&amp;lt;0.05 to pCRC in synchronous group 120 CD8 OM 206 559p&amp;lt;0.05 to pCRC 310 363 CD8 PT 177 369p&amp;lt;0.05 to pCRC 218 291 CD20 NM 331 215 CD20 TC 32p&amp;lt;0.05 to NM 11p&amp;lt;0.05 to NM 27p&amp;lt;0.05 to NM 12p&amp;lt;0.05 to NM and pCRC CD20 IM 20 39p&amp;lt;0.05 to pCRC 20 33 CD20 OM 137 327p&amp;lt;0.05 to pCRC 134 303p&amp;lt;0.05 to pCRC CD20 PT 153 224 196 213 Citation Format: Andriy Trailin, Wenjing Ye, Esraa Ali, Sergii Pavlov, Lenka Cervenkova, Filip Ambrozkiewicz, Ondrej Vycital, Ondrej Daum, Vaclav Liska, Kari Hemminki. Adaptive immune cells in colorectal cancer between normal mucosa, primary tumor and liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5528.

Unraveling the enigma: A comprehensive review of solid pseudopapillary tumor of the pancreas.

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm predominantly observed in young females. Pathologically, CTNNB1 mutations, β-catenin nuclear accumulation, and subsequent Wnt-signaling pathway activation are the leading molecular features. Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies. Surgical resection remains the mainstay treatment. Risk models, such as the Fudan Prognostic Index, show promise as predictive tools for assessing the prognosis of SPTP. Establishing three types of metachronous liver metastasis can be beneficial in tailoring individualized treatment and follow-up strategies. Despite advancements, challenges persist in understanding its etiology, establishing standardized treatments for unresectable or metastatic diseases, and developing a widely recognized grading system. This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology, clinical presentation, pathology, molecular characteristics, diagnostic methods, treatment options, and prognostic factors.

A nomogram prediction model based on clinicopathological combined radiological features for metachronous liver metastasis of colorectal cancer.

Objective: To establish a nomogram prediction model (based on clinicopathological and radiological features) for the development of metachronous liver metastasis (MLM) in patients with colorectal cancer (CRC). Methods: This retrospective study included patients with CRC who underwent surgery at Changshu No.1 People's Hospital and the Second Affiliated Hospital of Soochow University between January 2016 and December 2018. The clinical, pathological, and radiological features of each patient were investigated. Risk factors for MLM were identified by univariable and multivariable analyses. The predictive nomogram for MLM development was constructed. The predictive performance of the nomogram was estimated by the receiver operating characteristics curve, calibration curve, and decision curve analysis. Results: This study included 161 patients with CRC [median age: 66 (range, 33-87) years]. Fifty-nine developed MLM after a median of 12 (range, 2-52) months after surgery. The multivariable logistic regression analysis showed that age >66 years (OR=3.471, 95% CI: 1.272-9.473, P=0.015), N2 stage (OR=6.534, 95% CI: 1.456-29.317, P=0.014), positive vascular invasion (OR=2.995, 95% CI: 1.132-7.926, P=0.027), positive tumor deposit (OR=4.451, 95% CI: 1.153-17.179, P=0.030), and linear (OR=6.774, 95% CI: 1.306-35.135, P=0.023) and nodal pericolic fat infiltration patterns (OR=8.762, 95% CI: 1.521-50.457, P=0.015) were independently associated with MLM. These five factors were used to create a nomogram. The area under the receiver operating characteristics curve of the nomogram was 0.866 (95% CI: 0.803-0.914), indicating favorable prediction performance. The calibration curve of the nomogram showed a satisfactory agreement between the predicted and actual probabilities. Conclusions: A nomogram prediction model based on five clinicopathological and radiological features might have favorable prediction performance for MLM in patients who underwent surgery for CRC. Hence, the present study proposes a nomogram that can easily be used to predict MLM after CRC surgery based on readily available features.

Hepatic steatosis predicts metachronous liver metastasis in colorectal cancer patients: a nested case-control study and systematic review.

Nearly twenty-five percent of colorectal cancer (CRC) patients develop metachronous colorectal liver metastasis (CRLM) after curative surgery. Hepatosteatosis is the most prevalent liver condition worldwide, but its impact on the incidence of metachronous CRLM is understudied. In the present study, we aimed to investigate the predictive value of hepatic steatosis on the development of metachronous CRLM. First, a nested case-control study was conducted, enrolling stage I to III CRC patients in the National Colorectal Cancer Cohort (NCRCC) database. Metachronous CRLM patients and recurrence-free patients were matched via propensity-score matching. Fatty liver was identified based on treatment-naïve CT scans and the degree of hepatic fibrosis was scored. Multivariable analysis was conducted to investigate the association between fatty liver and metachronous CRLM. In our database, a total of 414 patients were included. Metachronous CRLM patients had considerably higher rates of hepatic steatosis (30.9% versus 15.9%, P<0.001) and highly fibrotic liver (11.6% versus 2.9%, P=0.001) compared to recurrence-free patients. Multivariable analysis showed that fatty liver (odds ratios [OR]=1.99, 95% confidence interval [CI] 1.19-3.30, P=0.008) and fibrotic liver (OR=4.27, 95% CI 1.54-11.81, P=0.005) were associated with high risk of metachronous CRLM. Further, a systematic literature review was performed to assess available evidence on the association between hepatosteatosis and development of metachronous CRLM. In the systematic review, 1815 patients were pooled from eligible studies, and hepatic steatosis remained a significant risk factor for metachronous CRLM (OR=1.90, 95% CI 1.35-2.66, P<0.001, I2=25.3%). In conclusion, our data suggest that patients with a steatotic liver and a high fibrosis score at CRC diagnosis have elevated risk of developing metachronous CRLM.

NEOADJUVANT TREATMENT OF LIVER METASTASES OF COLORECTAL CANCER: PREDICTIVE FACTORS OF PATHOLOGICAL RESPONSE.

Surgery after neoadjuvant chemotherapy (CT) improves the prognosis of colorectal liver metastases (CRLM). The aim of this study was to evaluate the predictive factors of the histological response of CRLM after neoadjuvant treatment. A retrospective monocentric study including patients with CRLM operated after neoadjuvant treatment. Assessment of histological response was based on the Rubbia-Brandt tumor regression grading score. The scores were grouped into two types of response: Response Group (R) and No Response Group (NR). The study included 77 patients (mean age=56 years, sex ratio=1.57). Node metastases were noticed in 62% of cases. Synchronous liver metastasis was present in 42 cases (55%) and metachronous liver metastasis in 45%. Neoadjuvant treatment consisted of CT only in 52 patients (68%) and CT with targeted therapy in 25 patients (32%). Chemo-induced lesions were present in 44 patients (57%). Histological response was presented (Group R) in 36 cases (47%) and absent (Group NR) in 41 cases (53%). The overall survival of our patients was 32 months. For Group R, survival was significantly greater (p=0.001). The predictive factors of histological response identified were delay in the onset of liver metastasis greater than 14 months (p=0.027) and neoadjuvant treatment combining CT and targeted therapy (p=0.031). In multivariate analysis, the type of neoadjuvant treatment (p=0.035) was an independent predictive factor of histological response. Predictive factors of histological response would allow us to identify patients who would benefit most from neoadjuvant treatment. These patients with CRLM onset of more than 14 months and treated with CT combined with targeted therapy would be the best candidates for a neoadjuvant CT strategy followed by surgical resection.

Manganese-based microcrystals equipped with Ythdf1-targeted biomimetic nanovaccines for reinforced dendritic cell spatiotemporal orchestration

Undesired dendritic cell (DC) spatiotemporal orchestration and innate immune stimulation severely dampens anti-tumor efficacy of cancer vaccines. Here, we develop a manganese-based (Mn2+) metal-organic framework (MOF) microcrystal equipped with Ythdf1-targeted biomimetic nanovaccines to create an in situ proinflammatory immune niche for augmented DC spatiotemporal orchestration. The bimetallic MOF microcrystal serves as a self-adjuvanting delivery platform that cannot only gradually release tumor-associated antigens and Mn2+, but also create an in situ immune niche for DC spatiotemporal orchestration including recruitment (particularly for DC1s, cross-presenting antigens to CD8+ T cells), activation, and lymph node migration. Benefitting from the Mn2+-mediated cGAS-STING activation together with Ythdf1 downregulation-induced antigen cross-presentation reinforcement, the vaccines elicit robust prophylactic efficacy for delaying B16-OVA and MC38 tumor occurrence, and show potent therapeutic efficacy for suppressing postoperative MC38 tumor recurrence and metachronous liver metastasis. Our study provides a versatile and powerful approach for fabricating personalized scaffold cancer vaccines.

Occult Vertebral Fracture (OVF) in Patients Who Underwent Hepatectomy for Colorectal Liver Metastasis: Strong Association with Oncological Outcomes

Aim: The impact of occult vertebral fracture (OVF) on oncological outcomes after surgery has not been investigated, although its significance in orthopedics has been much debated recently. We evaluated the prognostic significance of OVF on the long-term outcomes of patients with colorectal liver metastases (CRLM) after hepatectomy. Methods: We included 140 patients with CRLM who underwent hepatectomy. OVF was identified using quantitative measurement and preoperative sagittal computed tomography image reconstruction from the 11th thoracic vertebra to the 5th lumber vertebra. Results: OVF was identified in 48 (34%) of the patients. In multivariate analysis, lymph node metastases (p &lt; 0.01), multiple tumors (p = 0.02), extrahepatic lesions (p &lt; 0.01), OVF (p &lt; 0.01), intraoperative bleeding (p = 0.04), and curability 1 or 2 (p &lt; 0.01) were independent and significant predictors of disease-free survival and extrahepatic lesions (p &lt; 0.01), osteosarcopenia (p = 0.02), and OVF (p &lt; 0.01) were independent and significant predictors of overall survival. A higher age, adjuvant chemotherapy for a primary lesion before metachronous liver metastases, osteopenia, and hypoalbuminemia were independent risk factors for OVF. Conclusions: The evaluation of preoperative OVF is a useful prognostic factor for risk stratification and clinical decision-making for patients with CRLM.

Two cases of colorectal liver metastasis with residual liver recurrence after a long recurrence-free survival period

BackgroundThe rate of residual liver recurrence after the resection of colorectal liver metastases is high, and most cases recur within 5 years of the initial hepatectomy. Here, we report two cases of residual liver recurrence after radical resection of colorectal liver metastases after a long recurrence-free survival period.Case presentationCase 1 involved a 62-year-old woman treated for ascending colon cancer in April 2011 who underwent right hepatectomy for synchronous colorectal liver metastasis in April 2012. However, in September 2021, computed tomography revealed residual recurrence in the lateral segment of the liver, and a lateral segmentectomy of the liver was performed. In Case 2, a 52-year-old man treated for cecal cancer in July 2002 underwent lateral segmentectomy of the liver for metachronous colorectal liver metastasis in October 2006. Subsequently, there was no recurrence; however, computed tomography showed residual liver recurrence in the right lobe of the liver in October 2021, and an expanded posterior hepatic segmentectomy was performed.Histopathological findings in both cases were consistent with colorectal liver metastases.ConclusionsWe encountered two cases in which residual liver recurrence was observed after a long period of recurrence-free survival. Although rare, there have been a few cases of late recurrence of liver metastases after radical resection of cancer liver metastases.

Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.