Curative-intent Resection Research Articles

Mass-forming intrahepatic cholangiocarcinoma: treatment outcomes after curative-intent resection in an Australian tertiary referral hospital.

Mass-forming intrahepatic cholangiocarcinoma (MF-ICC) is the second most common primary liver cancer and liver resection offers the best chance of possible cure. This study aimed to assess treatment outcomes and prognostic factors for long-term survival in patients who underwent curative-intent liver resection. A retrospective analysis was conducted on prospectively collected data from patients with MF-ICC managed at the Royal North Shore/North Shore Private Hospital from January 1998 to October 2023. Baseline, peri-operative and long-term outcomes have been analysed, including an overall survival (OS) and disease-free survival (DFS) analysis. During the 25-year study period, 47 patients underwent curative-intent liver resection for primary MF-ICC at a median age of 70 years. The median OS was 36 months, with a 5-year OS of 33%. Multiple liver tumours (HR = 2.84; 95% CI = 1.24-6.48; P = 0.013) and a positive resection margin (HR = 2.46; 95% CI = 1.10-5.52; P = 0.029) were identified as independent predictors of poor long-term OS. Recurrence occurred in 62% of patients after a median DFS of 16 months, with poor tumour differentiation (HR = 3.93; 95% CI = 1.62-9.54; P = 0.002) and elevated tumour markers (HR = 3.47; 95% CI = 1.53-7.87; P = 0.003) as independent predictors of poor DFS. Liver resection can offer a significant chance for prolonged survival in a highly selected population of patients with MF-ICC. However, the surgical challenges inherent in treating this rare disease are evident, emphasizing the need for a multimodal approach and continued exploration of additional therapies to enhance personalized treatment strategies.

Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice.

Many patients with hepatocellular carcinoma (HCC) experience recurrence after curative-intent resection or ablation, with a poor prognosis. Real-world patterns of recurrence and the prognostic significance of early recurrence in U.S. clinical practice have not been well characterized. This retrospective observational study was designed to evaluate the impact of recurrence on overall survival (OS) among patients with HCC following initial curative-intent resection or ablation. We used the Surveillance, Epidemiology, and End Results cancer registry linked with Medicare claims (January 1, 2010-December 31, 2019). Eligible patients (≥66 years) diagnosed with HCC (2010-2017) had liver resection or ablation within 180 days of diagnosis. Patients were stratified by recurrence status using diagnosis- and treatment-based definitions of recurrence. Early or late recurrence was defined as within 1 year or after 1 year, respectively. Adjusted OS analyses used multivariable Cox regression models. A total of 1,146 patients were included. During a median overall follow-up of 35.2 months, 736 (64%) patients had a recurrence, of whom 380 (52%) had early recurrence (within 1 year). In the adjusted analysis, patients with recurrence had a 2.24-fold higher risk of death (95% confidence interval 1.85, 2.71; P < 0.001). Patients with early recurrence had a 1.39-fold higher risk of death (95% confidence interval 1.14, 1.68; P < 0.001) than those with late recurrence. Recurrence and the timing of recurrence are significant predictors of increased mortality risk for patients with HCC following initial curative-intent resection or ablation, highlighting the need for effective adjuvant therapies that may delay or avoid recurrences.

KRAS Variants Are Associated With Survival Outcomes and Genomic Alterations in Biliary Tract Cancers.

KRAS variants are associated with poor outcomes in biliary tract cancers (BTCs). This study assesses the prevalence of KRAS variants and their association with survival and recurrence in patients with intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder adenocarcinoma (GB). In this cross-sectional, single-institution study at Memorial Sloan Kettering, tumors from 985 patients treated between 2004 and 2022 with IHC, EHC, and GB who underwent either curative-intent resection or were treated with chemotherapy for unresectable disease were used for targeted sequencing. Of the 985 patients sequenced, 15% had a KRAS mutation. Five hundred and seventy-two had unresectable disease (n = 395 IHC, n = 71 EHC, n = 106 GB) and 413 were treated with curative-intent resection (n = 175 IHC, n = 119 EHC, and n = 119 GB). Median follow-up time was 18 months (IQR, 11-31). KRAS G12D mutations were most common in IHC (38%) and EHC (37%) tumors. Mutations in SF3B1 co-occurred with mutant KRAS in IHC and EHC, with comutant resectable patients having worse survival after adjusting for tumor type (hazard ratio [HR], 4.04 [95% CI, 1.45 to 11.2]; P = .007). KRAS G12 mutations were associated with worse survival in patients with IHC compared with wild-type (WT) or other KRAS mutations, regardless of resection status (unresectable P < .001, resectable P = .011). After adjusting for clinical covariates, KRAS G12 mutations remained a prognostic indicator for patients with IHC compared with WT (HR, 1.99 [95% CI, 1.41 to 2.80]; P < .001). The adverse impact of KRAS mutations in BTC is driven by G12 alterations in patients with IHC regardless of resection status, which was not observed in GB or EHC. There are unique comutational partners in distinct BTC subsets. These differences have important clinical implications in the era of KRAS-targeted therapeutics.

Presentation, Treatment, and Survival Among Asians With Gastric Cancer

IntroductionIn aggregate, Asian patients have a higher incidence and mortality from gastric cancer (GC) than Non-Hispanic White (NHW) patients. However, there is a lack of data regarding outcomes among Asian-American subpopulations with GC. MethodsThe National Cancer Database was used to identify patients with GC between 2004 and 2020. Asian patients were disaggregated by region, with a further subanalysis of Eastern Asians. Outcomes of interest included the initial localized/regional presentation versus metastatic disease and cancer care measures including undergoing surgical excision or resection for stages I-III, receiving guideline-concordant care, receiving delayed treatment (> 90 days for any treatment type), and overall survival. Outcomes were adjusted for patient/disease characteristics, treatment, and zip-code socioeconomic factors using logistic regression. ResultsAmong 182,811 patients with GC, 7.2% (n = 13,051) were classified as Asian. More than one-half of the Asian cohort was categorized as East Asian (n = 6,762, 50.1%), with Chinese patients compromising 44.0% (n = 2972) of this subcohort. East Asian patients had greater odds of presenting with nonmetastatic disease (odds ratio [OR] 1.59; P < 0.001), undergoing a curative-intent resection (OR 1.52; P < 0.001), and receiving guideline-concordant care (OR 1.26; P < 0.001) compared to NHW patients. Asians from outside of East, Southeast, and South Asia had increased odds of delayed treatment (OR 1.29, P = 0.024). Asians, in aggregate and by each subpopulation, had a lower mortality risk than NHW patients (P < 0.001). ConclusionsAsian patients with GC have improved outcomes in aggregate compared to NHW patients, largely driven by the East Asian subpopulation. All Asian subpopulations demonstrated improved survival in comparison with NHW patients.

Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma.

BackgroundCholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system, which can be classified into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). Surgical resection is the curative treatment for all subtypes of CCA. This study evaluates patients with CCA who underwent surgery and determines factors that impact their survival.MethodsWe conducted a retrospective analysis of 720 patients diagnosed with CCA from October 2013 to December 2018. Patients were categorized into iCCA (n = 398), pCCA (n = 237), and dCCA (n = 85) based on tumor location. Data including demographic information, clinical presentation, treatment modalities, and survival statistics were collected and analyzed.ResultsThe overall resectability rate was 78.3%, with resectability highest in pCCA patients (83.5%). Overall median survival time (MST) was 11.6 months and varied among subtypes: iCCA 10.9 months, pCCA 11.2 months, and dCCA 15.4 months. Patients underwent curative-intent resection significantly improved survival compared to those with palliative resection or unresectable disease in all subtypes. R0 resection patients had better overall survival (OS) than R1 resection patients: 5-year survival rate of 20.2% vs. 4.3% in all CCA (p < 0.001), 21.4% vs. 7% in iCCA (p < 0.001), 17.2% vs. 0% in pCCA (p < 0.001), and 23.1% vs. 0% in dCCA (p = 0.105), respectively. Positive resection margin was an independent prognostic factor for OS in pCCA and iCCA.ConclusionSurgical resection is the only cure for CCA. Curative-intent resection is more effective than palliative resection in improving survival rates. When performing curative-intent resection, the goal is R0 resection. This is because it improves overall survival over R1 resection.

Basal metabolic rate by FAO/WHO/UNU as a prognostic factor for survival in patients with gastric cancer: A cohort study

The basal metabolic rate (BMR) is a crucial indicator of the body’s energy expenditure at rest and is essential for understanding metabolic needs. This retrospective study evaluated the prognostic significance of BMR in 521 predominantly Asian patients with stage I–III gastric cancer who underwent curative-intent resection. BMR was calculated using the Food and Agriculture Organization/World Health Organization/United Nations University (FWU BMR) equation. Multivariate Cox regression analysis identified FWU BMR as a significant predictor of overall survival (OS) (P &lt; .001). Fractional polynomial modeling revealed a linear relationship between FWU BMR and OS, with higher values correlating with lower mortality risk. The FWU model, which included FWU BMR along with other clinical variables, showed superior predictive performance (C-index: 0.815, iAUC: 0.775) compared to that of the same model lacking BMR. Additionally, although the differences were not statistically significant, the FWU model also outperformed those using the BMR derived from alternative equations, including the Harris–Benedict equation. The nomogram, based on the FWU model, demonstrated good calibration. These findings suggest that the FWU BMR is a valuable prognostic factor in patients with gastric cancer post-resection, enhancing predictive accuracy and aiding in personalized post-surgical care. However, further validation in diverse populations is required.

Recurrence Timing and Risk Following Curative Resection of Colorectal Liver Metastases: Insights From a Hazard Function Analysis.

There is no consensus on the optimal surveillance interval for patients undergoing resection of colorectal liver metastases (CRLM). We sought to assess the timing and intensity of recurrence following curative-intent resection of CRLM utilizing a recurrence-free survival (RFS) hazard function analysis. Patients with CRLM who underwent curative-intent resection were identified from a multi-institutional database. The RFS hazard function was used to plot hazard rates and identify the peak of recurrence over time. Among 1804 patients, the median RFS was 19.9 months. In the analytic cohort, the RFS hazard curve peaked at 5.9 months (peak hazard rate: 0.054) and gradually declined, indicative of early recurrence. In subgroup analyses, patients with high and medium tumor burden scores (TBS) had RFS hazard peaks at 4.9 months (peak hazard rate: 0.060) and 5.8 months (peak hazard rate: 0.054), respectively. In contrast, patients with low TBS had a later peak at 7.5 months, with the lowest peak hazard rate of 0.047. The recurrence peak for CRLM patients occurred approximately 6 months postsurgery, highlighting the need for intensified early postoperative surveillance. Patients with high TBS experienced earlier recurrence, underscoring the importance of close monitoring, particularly during the first 6 months after surgery.

ASO Author Reflections: Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer

ASO Author Reflections: Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer

Advantage of Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Lymph node metastasis (LNM) is among the most important predictors of poor prognosis after surgery for gallbladder cancer (GBC). Traditionally, staging has been based on the raw count of LNM, with a high risk of understaging patients who undergo inadequate lymph node dissection (LND). The log odds of metastatic lymph nodes (LODDS) may represent an alternative staging approach to stratify patients more accurately after resection of GBC. In this cross-sectional study, patients who underwent curative-intent surgery with LND for GBC were identified from an international database. Two predictive models were built and compared, each integrating a different lymph nodes status indicator [i.e., American Joint Committee on Cancer (AJCC) and LODDS]. Among 199 patients, the median number of lymph nodes examined was 5 [interquartile range (IQR): 3.0, 8.0]; most patients had T1 (n = 26, 13.1%) or T2 (n = 97, 48.7%) disease, and a subset had LNM (n = 87, 44.0%). Multivariable Cox analysis demonstrated LODDS was an independent predictor of overall survival [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.5-2.3; p < 0.001]. The LODDS model demonstrated better performance compared with a traditional model that utilized the AJCC N category [concordance (C) index: 0.814 versus 0.763; p < 0.001]. Patients classified as high- versus low-risk based on LODDS had much worse overall survival (OS) (4.9% versus 83.7%, respectively; p < 0.001). The LODDS model performance remained high even among patients with inadequateLND (< 6 LN) (C index: 0.87). An online calculator was developed ( https://catalano-giovanni.shinyapps.io/LoddsGBC/ ). A novel prognostic model based on LODDS may overcome the inherent limitations of the current AJCC staging system, reducing understaging among patients with fewer than six total lymph nodes evaluated.

OGC SO34 - Textbook Outcome in Gastric Cancer Elective Surgery: A multicentre analysis

Abstract Background Textbook outcome (TO) is a composite measure of surgical outcomes that, when collectively achieved, depict the optimal result for the patient. Multidimensional parameters, like TO offer a in depth picture of hospital performance, by combining multiple indicators. While an increasing number of studies are evaluating TO in cancer, its application for gastric cancer is still a recent advance. Since surgical reality differs worldwide, a common language is essential when setting outcome goals. This study aims to assess TO accomplishment in several hospital typologies that offer curative-intent resections for gastric cancer. Method A prospective observational multi-institutional audit and 90 day follow-up included data from 138 institutions, in 47 countries. This is a preliminary analysis with focus on TO. Adult patients who underwent elective gastric cancer resection with curative intent, between April 1st and September 30th, 2022, were included. Textbook Outcome (TO) was achieved when all the following seven criteria were met: complete resection (R0), more than 15 lymph nodes sampled, discharge before 21 days, no mortality, no severe morbidity (Clavien–Dindo over 2), no reintervention and no readmission within 90 days post-operative. Results A total of 380 collaborators submitted data on 1538 patients. The mean age was 64.2 years and 58.5% were males. A total of 734 (48%) from the included 1538 patients, achieved TO. “No reintervention in 90 days” was registered in 92% of patients. “No morbidity in 90 days” was observed in 71%. “More than 15 lymph nodes sampled" was achieved in only 79%. The 90-day morbidity and mortality rates were 38.2% (n=587) and 2.9% (n=45), respectively. Conclusion This study demonstrates that achieving Textbook Outcome in gastric cancer resection is seldom attainable. A significant variability across the different outcome parameters within the participating centres was expected. The high rates of mortality-free and reintervention-free outcomes express an effective postoperative care. The lower rates of adequate lymph node sampling and morbidity-free outcomes indicate areas for improvement. Further research should focus on standardizing protocols and improving specific surgical practices to enhance overall TO rates in gastric cancer patients, among the hospital typologies and geographic locations, included in this study.

Impact of Socioeconomic Deprivation on Care Quality and Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer in United States Veterans.

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI > 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732-0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502-0.698) and PFT (aOR 0.816, 95% CI 0.694-0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103-1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750-0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911-1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930-1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC.

Risk of metachronous peritoneal metastases after surgery for obstructive colon cancer: Multivariate analysis from a series of 1,085 patients

BackgroundData in the literature suggest that obstruction is an independent predictor of poor prognosis in colon cancer. Of all possible sites of recurrence, peritoneal metastases are associated with worse survival. Our aim was to report the incidence of metachronous peritoneal metastases from a cohort of patients undergoing resection of obstructive colon cancer with curative intent and to identify predictive factors for metachronous peritoneal metastases. MethodsFrom 2000 to 2015, a total of 2,325 patients were treated for obstructive colon cancer in French surgical centers, members of the French National Surgical Association (AFC). Patients with palliative management, synchronous metastatic disease, and with postoperative mortality were excluded. A multivariate analysis was performed to determine independent predictive factors of metachronous peritoneal metastases. ResultsThe cohort included 1,085 patients. The median follow-up was 21.5 months. Metachronous peritoneal metastases occurred in 12% of patients and were diagnosed after a median interval of 13.5 months. The cumulative 3-year metachronous peritoneal metastasis rate was 10.9%. Three-year overall survival was 85% for patients who did not develop recurrence, 71% for those who develop recurrence without peritoneal metastases, and 56% for those with metachronous peritoneal metastases (P < .0001). In multivariate analysis, 3 variables were identified as independent risk factors for metachronous peritoneal metastases: pT4 stage (odds ratio: 1.98; 95% confidence interval: 1.17–3.36; P = .011), pN2 stage (odds ratio: 2.57; 95% confidence interval: 1.89–4.45; P = .0007), and fewer than 12 lymph nodes examined (odds ratio: 2.01; 95% confidence interval: 1.08–3.74; P = .028). ConclusionThis study showed a significant risk of metachronous peritoneal metastases after curative-intent resection of obstructive colon cancer. The awareness of factors predisposing to metachronous peritoneal metastases could improve the treatment strategy of these patients.

Lymphadenectomy for Perihilar Cholangiocarcinoma: Therapeutic Benefit of Lymph Node Number and Station

INTRODUCTIONWe sought to characterize the benefit of lymphadenectomy among patients undergoing curative-intent surgery for perihilar cholangiocarcinoma (pCCA) utilizing the therapeutic index. METHODSData on patients who underwent curative-intent resection for pCCA between 2000-2023 were obtained from 8 high-volume international hepatobiliary centers. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with overall survival (OS). The therapeutic index was determined to assess the therapeutic benefit of lymphadenectomy. RESULTSAmong 341 patients, median number of LNs evaluated was 7 (IQR: 4-11). A total of 127 (37.2%) patients underwent lymphadenectomy of station 12 only, while 146 (42.8%) patients had LNs from stations 12 plus 8 ± 13 harvested. On multivariable analysis, lymphadenectomy of stations 12 plus 8 ± 13 was associated with improved OS (referent, station 12 only: HR 0.51, 95%CI 0.32-0.80). The therapeutic index was highest among patients who underwent LN evaluation of stations 12 plus 8 ± 13 (33.1) and had ≥ 6 LNs harvested (26.3). CONCLUSIONSAt the time of surgery of pCCA, lymphadenectomy should include station 12, as well as stations 8 and 13, with the goal to evaluate > 6 LNs to ensure optimal staging and maximize the therapeutic benefit for patients.

Classifying histopathological growth patterns for resected colorectal liver metastasis with a deep learning analysis.

Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides. The algorithm was developed using digitalized whole-slide images obtained in a single-centre (Erasmus MC Cancer Institute, the Netherlands) cohort of patients who underwent first curative intent resection for colorectal liver metastases between January 2000 and February 2019. External validation was performed on whole-slide images of patients resected between October 2004 and December 2017 in another institution (Radboud University Medical Center, the Netherlands). The outcomes of interest were the automated classification of dichotomous hepatic growth patterns, distinguishing between desmoplastic hepatic growth pattern and non-desmoplatic growth pattern by a deep-learning model; secondary outcome was the correlation of these classifications with overall survival in the histopathology manual-assessed histopathological growth pattern and those assessed using neural image compression. Nine hundred and thirty-two patients, corresponding to 3.641 whole-slide images, were reviewed to develop the algorithm and 870 whole-slide images were used for external validation. Median follow-up for the development and the validation cohorts was 43 and 29 months respectively. The neural image compression approach achieved significant discriminatory power to classify 100% desmoplastic histopathological growth pattern with an area under the curve of 0.93 in the development cohort and 0.95 upon external validation. Both the histopathology manual-scored histopathological growth pattern and neural image compression-classified histopathological growth pattern achieved a similar multivariable hazard ratio for desmoplastic versus non-desmoplastic growth pattern in the development cohort (histopathology manual score: 0.63 versus neural image compression: 0.64) and in the validation cohort (histopathology manual score: 0.40 versus neural image compression: 0.48). The neural image compression approach is suitable for pathology-based classification tasks of colorectal liver metastases.

Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach.

Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM). Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values. Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4months (interquartile range [IQR] 29.9-46.7) versus 120.5months (IQR 97.2-134.0), respectively (p<0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/. An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

Relationships between tumor CD147 expression, tumor-infiltrating lymphocytes, and oncostatin M in hepatocellular carcinoma.

In hepatocellular carcinoma (HCC), CD147 expression contributes to tumor malignancy; however, its relationship with the tumor-immune microenvironment (TIME) remains unclear. This study aimed to elucidate the clinicopathological characteristics associated with CD147 expression in HCC and investigate its association with the TIME, specifically its association with tumor-infiltrating lymphocytes (TILs) and oncostatin M (OSM). Using 397 HCC specimens from patients undergoing curative-intent resection, we assessed CD147 expression in tumor cells and quantified OSM-positive cells and various TILs (CD8+, CD4+, FOXP3+, and CD20+ cells) in the TIME. Using tissue microarrays, these assessments were performed through immunohistochemical analysis. We investigated the associations between CD147 expression status, the density of OSM-positive cells, and the densities of various TILs. High CD147 expression, found in 332 specimens (83.6%), was associated with advanced clinical stage (P = 0.029), fibrosis (P = 0.036), and higher densities of FOXP3+ cells (P = 0.0039), CD4+ cells (P = 0.0012), and OSM-positive cells (P = 0.0017). In CD147-high tumors, OSM-positive cell density was associated with all assessed TIL subsets (CD8+, CD4+, FOXP3+, and CD20+ cells; all Ps < 0.001), whereas in CD147-low tumors, OSM-positive cell density was associated only with FOXP3+ cells (P = 0.0004). In HCC, CD147 expression is associated with an immunosuppressive TIME, characterized by increased FOXP3+ regulatory T cells and a correlation with OSM-positive cells. These results elucidate the potential mechanisms through which CD147 facilitates tumor-immune evasion, suggesting the CD147 - OSM axis as a promising target for therapeutic intervention in HCC.

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors.

To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs). Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated. A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c ≥ 6.5% were included. Patients with HbA1c ≥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001). Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.

Feasibility of ctDNA in detecting minimal residual disease and predicting recurrence for colorectal cancer liver metastases.

Approximately 50% of patients diagnosed with colorectal cancer develop colorectal cancer liver metastases (CRLM). Although curative intent liver resection provides 5-year survival of 40-50%, up to 70% of patients develop recurrence of CRLM. Detection of minimal residual disease (MRD) is essential for timely, optimized treatment. This study evaluated the feasibility and utility of using circulating tumor DNA (ctDNA) to identify MRD and predict disease recurrence. Patients with CRLM that underwent liver resection and had known KRAS or PIK3CA mutations were retrospectively identified. Serial blood samples were collected every 3 months following surgery for disease surveillance. ctDNA was isolated from the samples and analyzed with digital PCR (dPCR). KRAS and PIK3CA mutations were identified by dPCR in 29 patients over 115 timepoints. In patients with detectable ctDNA at time of liver resection, 81% (13/16) developed disease recurrence, while 46% (6/13) of the patients with undetectable ctDNA recurred (p=0.064). Presence of ctDNA was detected in 27.6% (8/29) of the initial postoperative samples. Radiologic recurrence was later diagnosed in 100% (8/8) of these patients, while 52% (11/21) who had undetectable ctDNA postoperatively recurred (p=0.026). Detectable ctDNA postoperatively was associated with a shorter disease-free survival (DFS) of 9 months vs 13 months in patients who had undetectable ctDNA (HR 2.95, 95% CI 1.16-7.49; p=0.02). Liquid biopsy using dPCR can identify low levels of ctDNA, enabling early detection of disease recurrence. Additionally, the presence of ctDNA postoperatively was predictive of recurrence. This study corroborates current literature and provides rational for moving toward a clinical trial using ctDNA and dPCR to detect MRD after CRLM resection.

Proteogenomic Characterization of Early Intrahepatic Recurrence after Curative-Intent Treatment of Colorectal Liver Metastases.

Clinical and pathological factors are insufficient to accurately identify patients at risk of early recurrence after curative-intent treatment of colorectal liver metastases (CRLM). This study aimed to identify candidate prognostic proteogenomic biomarkers for early intrahepatic recurrence after curative-intent resection of CRLM. Patients diagnosed with intrahepatic recurrence within 6 months of liver resection were categorized as the "early recurrence" group, while those who achieved a recurrence-free status for 10 years were designated as "durable remission". Comprehensive genomic and proteomic profiling of fresh frozen samples from these prognostically distinct groups was performed using the TruSight Oncology 500 assay and label-free data-dependent acquisition liquid chromatography-mass spectrometry. Genetic alterations were identified in 117 of the 523 profiled genes in patients with early recurrence. The most common somatic mutations linked to early recurrence were TP53 (88%), APC (71%), KRAS (38%), and SMAD4 (21%). SMAD4 alterations were absent in samples from patients with a durable remission. Calponin-2, versican core protein, glutathione peroxidase 3, fibulin-5, and amyloid-β precursor protein were upregulated more than 2-fold in early recurrence. Exploratory analysis of these proteogenomic biomarkers suggests that SMAD4, calponin-2, and glutathione peroxidase 3 may have the potential to predict early recurrence, enabling improved prognostication and precision oncology in CRLM.

Association between patient medications and postoperative outcomes in early-stage non-small cell lung cancer.

Currently, there is no consensus on how to comprehensively assess comorbidities in lung cancer patients in the clinical setting. Prescription medications may be a preferred comorbidity assessment tool and provide a simple mechanism for predicting postoperative outcomes for lung cancer. We examined the relationship between prescription medications and postoperative outcomes for early-stage non-small cell lung cancer (NSCLC). We conducted a retrospective cohort study of patients with clinical stage I NSCLC who underwent surgical resection in the Veterans Health Administration (VHA) between 10/01/2006 and 09/30/2016. Details of all outpatient prescriptions filled by patients within the VHA system from 1-year up to 14 days before surgery were collected. Medications were categorized using the Anatomical Therapeutic Chemical (ATC) Level One classification system. We assessed the association of medications prescribed in the year prior to surgery with postoperative adverse events (composite of death or major complication) at 30 and 90 days following surgery and overall survival (OS). We included 9,741 veterans in the analysis. The median number of prescription medications filled in the year preceding surgery was 11 (interquartile range: 7-16). In multivariable-adjusted analyses, a higher number of prescription medications was associated with increased risk of 30-day [multivariable-adjusted odds ratio (aOR): 1.016; 95% confidence interval (CI): 1.007-1.026] and 90-day postoperative adverse events (aOR: 1.015; 95% CI: 1.006-1.024) and decreased OS (adjusted hazard ratio: 1.019; 95% CI: 1.014-1.023). Within a subgroup of patients with a high comorbidity burden (Charlson-Deyo Comorbidity Index score of 6-8), a higher number of prescription medications was also associated with reduced OS (P<0.001). Patients prescribed medications from the ATC respiratory system class had elevated risk of postoperative adverse events at 30 days (aOR: 1.255; 95% CI: 1.095-1.439) and 90 days (aOR: 1.254; 95% CI: 1.097-1.434) compared to patients without these prescription medications. Significantly increased odds for 90-day postoperative adverse events were observed with each additional prescription medication from the ATC respiratory (aOR: 1.057; 95% CI: 1.027-1.088) and nervous system (aOR: 1.035; 95% CI: 1.005-1.066) classes. The number of medications prescribed preoperatively is associated with short- and long-term postoperative outcomes for early-stage NSCLC, even when adjusting for several covariates including age and comorbidity burden. Patients prescribed a higher number of medications acting primarily on the respiratory and nervous systems are at elevated risk for postoperative adverse events after curative-intent resection. Prescription medications may be a reliable tool to assess comorbidities and perioperative risk for patients with NSCLC.