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Background RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear. Methods Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS). Results We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3-9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS 3 or ≥ 9. Conclusions In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.

The most appropriate venous reconstruction method remains debatable when a long section of portal vein (PV) and/or superior mesenteric vein (SMV) must be resected in patients undergoing a pancreaticoduodenectomy (PD). The aim of the present study was to describe the technical details of the parachute technique, a modified end-to-end anastomotic maneuver that can be used in the above-mentioned circumstances, and to investigate its safety and feasibility. Patients who underwent venous reconstruction using the parachute technique after receiving a PD with PV resection for pancreatic cancer between January 2014 and March 2019 were retrospectively reviewed. For the parachute technique, the posterior wall was sutured in a continuous fashion while the stitches were left untightened. The stitches were then tightened from both sides after the running suture of the posterior wall had been completed, thereby dispersing the tension applied to the stitched venous wall when the venous ends were brought together and solving any problems that would otherwise have been caused by over-tension. The postoperative outcomes and PV patency were then investigated. Fifteen patients were identified. The median length of the resected PV/SMV measured in vivo was 5 cm (range, 3–6 cm). The splenic vein was resected in all the patients and was reconstructed in 13 patients (87%). The overall postoperative complication rate (≥ Clavien-Dindo grade I) was 60%, while a major complication (≥ Clavien-Dindo grade IIIa) occurred in 1 patient (7%). No postoperative deaths occurred in this series. The PV patency at 1 year was 87%. The parachute technique is both safe and feasible and is a simple venous reconstruction procedure suitable for use in cases undergoing PD when the distance between the resected PV and SMV is relatively long.

Beta-tricalcium phosphate (β-TCP) serves as a bone substitute in clinical practice because it is resorbable, biocompatible, osteointegrative, and osteoconductive. Particles of β-TCP are also inflammatory mediators although the mechanism of this function has not been fully elucidated. Regardless, the ability of β-TCP to stimulate the immune system might be useful for immunomodulation. The present study aimed to determine the effects of β-TCP particles on NLR family pyrin domain containing 3 (NLRP3) inflammasome complexes. We found that β-TCP activates NLRP3 inflammasomes, and increases interleukin (IL)-1β production in primary cultured mouse dendritic cells (DCs) and macrophages, and human THP-1 cells in caspase-1 dependent manner. In THP-1 cells, β-TCP increased also IL-18 production, and NLRP3 inflammasome activation by β-TCP depended on phagocytosis, potassium efflux, and reactive oxygen species (ROS) generation. We also investigated the effects of β-TCP in wild-type and NLRP3-deficient mice in vivo. Immune cell migration around subcutaneously injected β-TCP particles was reduced in NLRP3-deficient mice. These findings suggest that the effects of β-TCP particles in vivo are at least partly mediated by NLRP3 inflammasome complexes.

The improvement of effective multidrug agents has allowed more patients to undergo resection for pancreatic cancer (PC). In the conversion cases of initially unresectable PC after induction chemotherapy, pancreatic surgeons often encounter challenging vein resections cases such as those of long-segment portal vein (PV)/superior mesenteric vein (SMV) encasement or occlusion of the distal (caudal) SMV. Given the lack of consensus for the optimal approach for major vein resections and reconstructions in these situations, this review summarizes the literature on this topic and provides the best currently available approaches for challenging vein reconstruction cases. For long-segment PV/SMV encasement, tips for direct end-to-end anastomosis without grafts and the splenic vein (SpV) reconstruction to prevent left-side portal hypertension will be introduced. For distal SMV encasement, several bypass techniques to deal with collateralizations will be introduced. Even though some high-volume PC centers are obtaining favorable outcomes for challenging vein resection cases, existing evidence on this topic is limited. It is essential to organize the well-designed international multicenter studies for the small population of challenging vein resection cases. With the emergence of effective chemotherapies, the number of PC patients who can undergo curative resection is increasing. Achieving more successful vessel resection and reconstruction in the treatment of PC is a common goal that pancreatic surgeons should focus on together.

The oncologic advantage of anatomic resection (AR) for primary hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the clinical advantages of AR for primary HCC by using propensity score-matching and by assessing treatment strategies for recurrence after surgery. The study reviewed data of patients who underwent AR or non-anatomic resection (NAR) for solitary HCC (≤ 5 cm) in two institutions between 2004 and 2017. Surgical outcomes were compared between the two groups in a propensity score-adjusted cohort. The time-to-interventional failure (TIF), defined as the elapsed time from resection to unresectable/unablatable recurrence, also was evaluated. The inclusion criteria were met by 250 patients: 77 patients (31%) with AR and 173 patients (69%) with NAR. In the propensity score-matched populations (AR, 67; NAR, 67), the 5-year recurrence-free survival (RFS) for AR was better than for NAR (62% vs 35%; P = 0.005). No differences, however, were found in the 5-year overall survival between the two groups (72% vs 78%; P = 0.666). The 5-year TIF rates for the NAR group (60%) also were similar to those for the AR group (66%) (P = 0.413). In the cohort of 67 patients, curative repeat resection or ablation therapy was performed more frequently for the NAR patients (42%) than for the AR patients (10%) (P

Plasmacytoid dendritic cells (pDCs) promote viral elimination by producing large amounts of Type I interferon. Recent studies have shown that pDCs regulate the pathogenesis of diverse inflammatory diseases, such as cancer. Fatty acid-binding protein 5 (FABP5) is a cellular chaperone of long-chain fatty acids that induce biological responses. Although the effects of FABP-mediated lipid metabolism are well studied in various immune cells, its role in pDCs remains unclear. This study, which compares wild-type and Fabp5-/- mice, provides the first evidence that FABP5-mediated lipid metabolism regulates the commitment of pDCs to inflammatory vs tolerogenic gene expression patterns in the tumor microenvironment and in response to toll-like receptor stimulation. Additionally, we demonstrated that FABP5 deficiency in pDCs affects the surrounding cellular environment, and that FABP5 expression in pDCs supports the appropriate generation of regulatory T cells (Tregs). Collectively, our findings reveal that pDC FABP5 acts as an important regulator of tumor immunity by controlling lipid metabolism.

Background: The effect of intraindividual variability in lipid levels on the onset of acute coronary syndrome (ACS) remains uncertain. We evaluated the relationship between intraindividual variability in lipid levels and culprit lesion morphologies by optical coherence tomography (OCT). Methods and Results: Seventy-four consecutive patients with ACS whose cholesterol levels were assessed ≥3 times during outpatient visits before the onset of ACS were enrolled in the study; 222 patients without significant stenotic lesions were used as a control group. Based on OCT findings of culprit lesions, ACS patients were categorized into a plaque rupture ACS (PR-ACS) group (n=44) or a non-plaque rupture ACS (NPR-ACS) group (erosion or calcified nodule; n=30). Visit-to-visit variability in lipid levels was evaluated using the corrected variability independent of the mean (cVIM). Patients with ACS had significantly higher low-density lipoprotein cholesterol (LDL-C) levels and cVIM in LDL-C than the control group. The PR-ACS group had significantly higher mean LDL-C levels and greater cVIM in LDL-C than the control group. The PR-ACS group had a significantly higher cVIM than the NPR-ACS group, despite similar mean LDL-C levels. Multivariate analysis revealed that higher cVIM of LDL-C was an independent predictor of PR-ACS (odds ratio 1.06; P=0.018). Conclusions: In addition to the LDL-C level, greater visit-to-visit variability in LDL-C levels may be associated with the onset of ACS induced by plaque rupture.

Neoadjuvant therapy is used for borderline resectable pancreatic ductal adenocarcinoma (PDAC) with high risk of incomplete resection and early recurrence. Because distal PDAC is rare, the optimal criteria for neoadjuvant therapy specific for distal PDAC remain unclear. We hypothesized large distal PDAC would recur earlier than small distal PDAC. The aim of this study was to identify the risk factors for failure of upfront resection for resectable distal PDAC. The study cohort comprised 158 patients with resectable distal PDAC who underwent radical resection. The long-term outcomes were recurrence-free survival (RFS), disease-specific survival (DSS), and post-recurrence survival (PRS). R0 resection was achieved in 92% of patients, and median DSS for the entire cohort was 31 months. Among 103 patients who developed recurrence, 32 (31%) developed recurrence within 6 months. The median PRS and DSS for those with early recurrence was 6 and 10 months, respectively, compared with 11 and 30 months, respectively, for those with late recurrence (p = 0.017 and p 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p 4 cm remained a significant predictor of early recurrence (p 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection.

The histone methyltransferase SET domain-containing protein 8 (SETD8), which methylates histone H4 lysine 20 (H4K20) and non-histone proteins such as p53, plays key roles in human carcinogenesis. Our aim was to determine the involvement of SETD8 in endometrial cancer and its therapeutic potential and identify the downstream genes regulated by SETD8 via H4K20 methylation and the p53 signaling pathway. We examined the expression profile of SETD8 and evaluated whether SETD8 plays a critical role in the proliferation of endometrial cancer cells using small interfering RNAs (siRNAs). We identified the prognostically important genes regulated by SETD8 via H4K20 methylation and p53 signaling using chromatin immunoprecipitation sequencing, RNA sequencing, and machine learning. We confirmed that SETD8 expression was elevated in endometrial cancer tissues. Our in vitro results suggest that the suppression of SETD8 using siRNA or a selective inhibitor attenuated cell proliferation and promoted the apoptosis of endometrial cancer cells. In these cells, SETD8 regulates genes via H4K20 methylation and the p53 signaling pathway. We also identified the prognostically important genes related to apoptosis, such as those encoding KIAA1324 and TP73, in endometrial cancer. SETD8 is an important gene for carcinogenesis and progression of endometrial cancer via H4K20 methylation.

Purpose: To investigate the detailed relationship between high wall shear stress (WSS) and plaque rupture (PR) in longitudinal and circumferential locations.Methods: Overall, 100 acute coronary syndrome (ACS) patients whose culprit lesions had PR documented by optical coherence tomography (OCT) were enrolled. Lesion-specific three-dimensional coronary artery models were created using OCT data. At the ruptured portion, tracing of the luminal edge of the residual fibrous cap was smoothly extrapolated to reconstruct the luminal contour before PR. Then, WSS was computed from computational fluid dynamics analysis. PR was classified into central-PR and lateral-PR according to the disrupted fibrous cap location.Results: In the longitudinal 3-mm segmental analysis, multivariate analysis demonstrated that higher WSS in the upstream segment was independently associated with Upstream-PR and a thinner fibrous cap was independently associated with Downstream-PR. In PR cross-sections, PR region had a significantly higher average WSS than the non-PR region. In the cross-sectional analysis, peak WSS was most frequently observed in the lateral region (66.7%) in lateral-PR, whereas that in central-PR was most frequently observed in the central region (70%). Multivariate analysis demonstrated that the presence of peak WSS at the lateral region, thinner broken fibrous cap, and larger lumen area were independently associated with lateral-PR, while the presence of peak WSS at the central region and thicker broken fibrous cap were independently associated with central-PR.Conclusions: A combined approach with computational fluid dynamics simulation and morphological plaque evaluation by OCT might help predict future PR-induced ACS events.

Purpose After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after introduction of these measures (2009–2018), these data were not compared with the 30 years before 2009 (1979–2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods. Methods From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period. Results Retrospective IgG4 immunostaining of TFCP revealed 14 (43.8%) cases of AIP in the former 30 years versus 5 (45.5%) in the latter 10 years. There were 32 (6.7%) cases of TFCP among 675 patients in the former 30 years and 11 (0.9%) among 1289 patients in the latter 10 years. Conclusions When the TFCP ratio of pancreatic resections and the AIP ratio of TFCPs were compared between the two periods, the TFCP ratio was 4.7% versus 0.9% and the AIP ratio was 43.8% versus 45.5%, respectively. These findings indicate that IgG4 measurement and EUS-FNA are imperative for the diagnosis of TFCP.

Purpose It is rare to find surgically-resectable metastatic lesions that are limited to the pancreas, by preoperative imaging. In this retrospective study, we reviewed the histopathologic findings in pancreatic surgical resection specimens to determine the factors that contribute to the prognostic improvement of surgical treatment for pancreatic metastases. Methods From 1979 to 2018, 43 patients underwent pancreatic resection for metastatic tumors in the Department of Hepato-Biliary-Pancreatic Surgery of the Cancer Institute of the Japanese Foundation for Cancer Research. Survival curves were created using the Kaplan–Meier method, and comparisons of survival were performed using the log-rank test.Results Primary tumors comprised renal cell carcinoma (RCC), colorectal carcinoma (CRC), and miscellaneous malignancies (MM) in 23, 9, and 11 cases, respectively. Histopathologically, the patterns of metastases were classified as hematogenous (32), lymphatic (8), and peritoneal (3). Regarding the prognosis after metastasectomy of the pancreas, there were significant differences for disease-free interval (< 5 years versus ≥5 years) and primary tumor (RCC versus CRC/MM). The rate of secondary or accompanying lymph node metastasis around the main metastasis was 5/9 (56%) for CRC, 5/11 (45%) for MM, and 1/23 (4%) for RCC. Conclusion Survival outcomes are more favorable for disease-free intervals ≥ 5 years, pancreatic metastasis from RCC, and with lymphatic metastasis. Lymph node dissection is not strictly necessary for the surgical removal of pancreatic metastasis from RCC, whereas this is highly recommended for patients with metastasis from CRC or MM.

Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and are present in the blood, their identity is poorly characterized in vivo, limiting the identification of their origin in the blood. Since skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined markers that distinguish skeletal muscle-derived EVs (SkM-EVs) from others, whether skeletal muscle releases EVs in vivo and how much SkM-EVs account for plasma EVs remain poorly understood. In this work, we perform quantitative proteomic analyses on EVs released from C2C12 cells and human iPS cell-derived myocytes and identify potential marker proteins that mark SkM-EVs. These markers we identified apply to in vivo tracking of SkM-EVs. The results show that skeletal muscle makes only a subtle contribution to plasma EVs as their source in both control and exercise conditions in mice. On the other hand, we demonstrate that SkM-EVs are concentrated in the skeletal muscle interstitium. Furthermore, we show that interstitium EVs are highly enriched with the muscle-specific miRNAs and repress the expression of the paired box transcription factor Pax7, a master regulator for myogenesis. Taken together, our findings confirm previous studies showing that skeletal muscle cells release exosome-like EVs with specific protein and miRNA profiles in vivo and suggest that SkM-EVs mainly play a role within the muscle microenvironment where they accumulate.

Recent technological innovations have led to the development of methods for the rapid identification of high-affinity macrocyclic peptides for a wide range of targets; however, it is still challenging to achieve the desired activity and membrane permeability at the same time. Here, we propose a novel small molecule lead discovery strategy, ″Peptide-to-Small Molecule″, which is a combination of rapid identification of high-affinity macrocyclic peptides

Gut microbiota regulate physiological functions in various hosts, such as energy metabolism and immunity. Lactic acid bacteria, including Lactobacillus plantarum, have a specific polyunsaturated fatty acid saturation metabolism that generates multiple fatty acid species, such as hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and trans-fatty acids. How these bacterial metabolites impact host physiology is not fully understood. Here, we investigated the ligand activity of lactic acid bacteria-produced fatty acids in relation to nuclear hormone receptors expressed in the small intestine. Our reporter assays revealed two bacterial metabolites of γ-linolenic acid (GLA), 13-hydroxy-cis-6,cis-9-octadecadienoic acid (γHYD), and 13-oxo-cis-6,cis-9-octadecadienoic acid (γKetoD) activated peroxisome proliferator-activated receptor delta (PPARδ) more potently than GLA. We demonstrate that both γHYD and γKetoD bound directly to the ligand-binding domain of human PPARδ. A docking simulation indicated that four polar residues (T289, H323, H449, and Y473) of PPARδ donate hydrogen bonds to these fatty acids. Interestingly, T289 does not donate a hydrogen bond to GLA, suggesting that bacterial modification of GLA introducing hydroxy and oxo group determines ligand selectivity. In human intestinal organoids, we determined γHYD and γKetoD increased the expression of PPARδ target genes, enhanced fatty acid β-oxidation, and reduced intracellular triglyceride accumulation. These findings suggest that γHYD and γKetoD, which gut lactic acid bacteria could generate, are naturally occurring PPARδ ligands in the intestinal tract and may improve lipid metabolism in the human intestine.

Mucosal atrophy and enlarged folds of stomach by double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) are two major features of Helicobacter pylori-induced chronic gastritis. These were previously shown to be risk indicators of gastric cancer, but their predictability for clinicopathological characters of developed gastric cancer is unelucidated. In addition, evidence for decreasing the mortality of gastric cancer by appropriate follow-up of UGI screening is needed. The 5134 generally healthy UGI-XR examinees, who underwent follow-up UGI-XR or upper gastrointestinal endoscopy (UGI-ES) more than once, were prospectively observed for 10 years. At the beginning of follow-up, 1515 (29.5%) had mucosal atrophy and 990 (19.5%) had enlarged folds. For the serum anti-H. pylori IgG, 1301 (25.3%) were positive, 177 (3.4%) were possibly positive, and 3656 (71.2%) were negative. During the 10-year observation period, gastric cancer developed in 15 subjects, among which 13 had mucosal atrophy and 10 had enlarged folds. These two features were expectedly useful indicators for gastric cancer incidence, but they showed no significant association with tumor stage or histological type of developed cancer. Only one of the 5134 subjects died of gastric cancer during 10 years, which was significantly lower than the predicted number of gastric cancer death (6.78 for 10 years) according to the mortality rate in Japan. Neither mucosal atrophy nor enlarged folds of stomach showed a significant association with clinicopathological features of developed gastric tumors. Appropriate follow-up of cancer screening by UGI-XR or UGI-ES can reduce the risk of gastric cancer-related death.

A modified Fong clinical score (m-Fong CS) that includes the RAS mutation status has recently been proposed and offered an improved survival stratification of patients who undergo surgery and systemic chemotherapy for colorectal liver metastases (CLM). The aim of this study is to assess whether a CS that includes RAS status is influenced by whether patients receive perioperative chemotherapy. We created a new CS using multivariate analysis of data of patients who underwent hepatectomy for CLM for the first time between 2010 and 2016 at a single hospital (n = 341, 79% received perioperative chemotherapy). The resulting CS and m-Fong CS were then validated in the patient cohort at three other hospitals (n = 309). Furthermore, the applicability of the two CS in the total cohort (n = 650) was tested according to whether the patients received perioperative chemotherapy. The new CS comprised mutant RAS status, ≥4 CLMs, and a CA19-9 level ≥100 U/mL (1 point per factor). Both the new CS and m-Fong CS failed to stratify the survival of the 309 patients in the validation cohort, including those who did not receive perioperative chemotherapy (29%). Both of the CS accurately stratified the survival of patients who underwent perioperative chemotherapy but not of those who underwent surgery alone. A CS that includes the RAS mutation status can stratify the survival of patients who undergo hepatectomy combined with perioperative chemotherapy, but it has limited value for patients who undergo surgery alone.

Although endoscopic naso-biliary drainage (ENBD) is a popular preoperative biliary drainage (PBD) method for patients with perihilar biliary malignancy (PHBM), patient discomfort caused by the nasal tube remains a problem. This study aimed to analyze the safety and efficacy of PBD with the placement of a plastic stent above the papilla [inside-stent (IS)] as a bridging therapy. The outcomes of 78 patients with potentially resectable PHBM, of whom 29 underwent IS placement and 49 underwent ENBD were evaluated. The stent-associated complication rates were not different between the two groups (7% in the IS group and 10% in the ENBD group, P = 0.621). Catheter dislocation occurred less frequently (0% vs. 22%, P = 0.016), and the median time to recurrent biliary obstruction was longer (not reached vs. 32 days, P = 0.039) in the IS group than in the ENBD group. Among the patients who underwent resection, their postoperative severe complication rates were not substantially different (26% vs. 25%, P = 0.923). IS placement is a possible alternative to ENBD as a bridge to a definitive operation for patients with resectable PHBM and a prospective trial to prove its feasibility and safety is therefore warranted.

Whether predicting the rotational atherectomy (RA) effect based on the position of optical frequency domain imaging (OFDI) is accurate remains uncertain. The aim of this study was to evaluate the predictive accuracy of OFDI in identifying RA location and area. Twenty-five patients who underwent RA with OFDI were included. On pre-RA OFDI images, a circle with the dimension of a Rota burr was drawn at the center of the OFDI catheter. The area where the circle overlapped with the vessel wall was defined as the predicted ablation area (P-area), and the actual ablated area (A-area) was measured. The predictive accuracy of OFDI was evaluated as follows: overlapped ablation area (O-area: overlapping P- and A-areas) divided by P-area = %Correct-area, and A-area − O-area divided by A-area = %Error-area. Cross-sections were separated into four categories based on the median values of %Correct- and %Error-area. Among 334 cross-sections, RA effects were confirmed in the predicted location in 87% of them. The median %Correct- and %Error-areas were 43.1% and 64.2%, respectively. Floppy wire, narrow lumen area, OFDI catheter close to the intima, and large arc of calcium were independently associated with good prediction (high %Correct-/low %Error-areas). Non-left anterior descending lesions, OFDI catheter far from the wire, and OFDI catheter and wire far from the intima were associated with irrelevant ablation (low %Correct-/ high %Error-areas). The accuracy of the OFDI-based predictions for RA effects was acceptable with regard to location, but not high with regard to area. Wire types, target vessels, and OFDI catheter and wire positions are important determinants for accurately predicting RA effect using pre-procedural OFDI.

INTRODUCTION: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) has been identified as a surrogate marker for vessel related adverse events. FFR can be derived from standard coronary computed tomography angiography (CTA). Moreover, the FFR derived from coronary CTA (FFRCT ) Planner is a tool that simulates PCI providing modeled FFRCT values after stenosis opening. AIM: To validate the accuracy of the FFRCT Planner in predicting FFR after PCI with invasive FFR as a reference standard. METHODS: Prospective, international and multicenter study of patients with chronic coronary syndromes undergoing PCI. Patients will undergo coronary CTA with FFRCT prior to PCI. Combined morphological and functional evaluations with motorized FFR hyperemic pullbacks, and optical coherence tomography (OCT) will be performed before and after PCI. The FFRCT Planner will be applied by an independent core laboratory blinded to invasive data, replicating the invasive procedure. The primary objective is to assess the agreement between the predicted FFRCT post-PCI derived from the Planner and invasive FFR. A total of 127 patients will be included in the study. RESULTS: Patient enrollment started in February 2019. Until December 2020, 100 patients have been included. Mean age was 64.1 ± 9.03, 76% were males and 24% diabetics. The target vessels for PCI were LAD 83%, LCX 6%, and RCA 11%. The final results are expected in 2021. CONCLUSION: This study will determine the accuracy and precision of the FFRCT Planner to predict post-PCI FFR in patients with chronic coronary syndromes undergoing percutaneous revascularization. ispartof: CLINICAL CARDIOLOGY vol:44 issue:4 pages:446-454 ispartof: location:United States status: published

Summary Metastasis is the major cause of cancer-related death, but whether metastatic lesions exhibit the same cellular composition as primary tumors has yet to be elucidated. To investigate the cellular heterogeneity of metastatic colorectal cancer (CRC), we established 72 patient-derived organoids (PDOs) from 21 patients. Combined bulk transcriptomic and single-cell RNA-sequencing analysis revealed decreased gene expression of markers for differentiated cells in PDOs derived from metastatic lesions. Paradoxically, expression of potential intestinal stem cell markers was also decreased. We identified OLFM4 as the gene most strongly correlating with a stem-like cell cluster, and found OLFM4+ cells to be capable of initiating organoid culture growth and differentiation capacity in primary PDOs. These cells were required for the efficient growth of primary PDOs but dispensable for metastatic PDOs. These observations demonstrate that metastatic lesions have a cellular composition distinct from that of primary tumors; patient-matched PDOs are a useful resource for analyzing metastatic CRC., Highlights • Seventy-two PDOs were established from 21 stage IV CRC patients • Forty-one DEGs were identified between primary and corresponding metastatic PODs • scRNA-seq analysis identified OLFM4 as a potential cancer stem cell marker • Different roles of OLFM4+ cells in primary and metastatic PDOs were demonstrated, In this article, Yao and colleagues show the cellular heterogeneity of PDOs derived from stage IV CRC. Primary PDOs possess more variable cellular hierarchy than corresponding metastatic/recurrent PDOs. OLFM4 is identified to be the gene most correlated to the stem cell-like clusters, and OLFM4+ cells are indispensable for the growth of primary PDOs.

Background Previous studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC. Methods We retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR). Results Overall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group. Conclusions It is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC.

The prediction of conversion surgery in patients with technically unresectable colorectal liver metastases has not been generalized or well-established. We developed a predictive model for conversion surgery and assessed the long-term outcomes of patients with technically unresectable colorectal liver metastases.In this single-center, retrospective study, we analyzed the perioperative parameters and outcomes of 892 consecutive patients (2014-2021). Conversion surgery was indicated when the chemotherapy response allowed the complete resection of colorectal liver metastases with negative margins and adequate remnant liver volume.Of the 892 patients, 122 had technically unresectable colorectal liver metastases; 61 underwent conversion surgery (conversion surgery group) and 61 did not (nonconversion surgery group). The median overall survival was significantly higher in the conversion surgery group than in the nonconversion surgery group (5.6 vs 1.8 years, P.001). After univariate and multivariate analyses, the predictive model for conversion surgery was constructed using 4 predictive factors: Rat sarcoma viral oncogene homolog status (mutant, +2 points), tumor number (≥15, +1), hepatic vein contact (≥2 hepatic veins, +1), and the presence of preservable sections (absence of preservable sections, +2). The area under the curve for conversion surgery was 0.889. Patients were graded according to the scores (A [0-2], B [3-4], and C [5-6]), and the conversion rates were 91.5% (A), 32.6% (B), and 10.3% (C) (P.001). Grade A patients (median survival time, 5.7 years) had significantly better overall survival than grade B and C patients (median survival time, 2.2 and 1.6 years, respectively; P.001).Patients who underwent conversion surgery for technically unresectable colorectal liver metastases had better prognoses, and our novel predictive model was useful in predicting conversion surgery and prognosis.