Efficacy of daratumumab in newly diagnosed multiple myeloma patients with 1q21 gain.

BACKGROUND: Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified. PATIENTS: We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022. RESULTS: The overall response rate was 82% for patients with 1q21+and 78% for patients without 1q21+. Median progression-free survival (PFS) and median overall survival (OS) were not reached in either group. Neither 1q21 copy number nor co-existence of other high-risk cytogenetic abnormalities significantly affected PFS or OS. CONCLUSION: Our preliminary data suggests that outcomes of daratumumab treatment in NDMM 1q21+patients might be non-inferior to those in non-1q21+patients.

Growth speed of large brain metastases between diagnostic and radiosurgical planning MRI and predictors of rapid tumor growth.

PURPOSE: We aimed to assess volumetric changes of large brain metastases (≥ 2 cm) between their diagnosis and planning for treatment with fractionated stereotactic radiation surgery (fSRS). Predictors of rapid tumor growth were also analyzed. MATERIALS AND METHODS: One hundred nine patients harboring 126 large brain metastases were retrospectively evaluated. Tumor characteristics were evaluated on diagnostic magnetic resonance imaging (dMRI) and MRI performed when planning fSRS (pMRI). Average tumor growth rate and percentage growth rate were calculated. Predictors of rapid growth (percentage growth rate > 5%) were determined using multivariate logistic regression. RESULTS: Both tumor diameter and volume were significantly larger on pMRI than on dMRI (P < 0.001). Median tumor percentage growth rate was 2.6% (range, - 10.8-43.3%). Eighty-eight tumors (70%) were slow-growing (percentage growth rate < 5%) and 38 (30%) grew rapidly (percentage growth rate ≥ 5%). Major peritumoral edema and no steroids were predictors of rapid tumor growth. CONCLUSION: Large brain metastases can grow considerably between the time of diagnosis and the time of fSRS treatment planning. We recommend the time between dMRI and fSRS treatment initiation be as short as possible.

Facile synthesis of 1,2-aminoalcohols via α-C-H aminoalkylation of alcohols by photoinduced hydrogen-atom transfer catalysis.

1,2-Aminoalcohols are common motifs found in a wide range of natural products and pharmaceutical compounds. Here we report a photocatalytic method for the direct conversion of readily available aliphatic alcohols into synthetically valuable 1,2-aminoalcohols. A dual catalytic system consisting of an acridinium photoredox catalyst and a cationic hydrogen-atom transfer (HAT) catalyst based on 1,4-diazabicyclo[2.2.2]octane (DABCO) enables an efficient and site-selective HAT from the α-C-H bonds of unprotected primary and secondary alcohols. The subsequent radical addition to a newly designed chiral N-sulfinyl α-iminoester afforded various 1,2-aminoalcohols, including enantiomerically enriched ones, under mild photochemical conditions with high atom and step economy.

Anatomical and anastomotic viability indexes for stratifying the risk of anastomotic leakage in esophagectomy with retrosternal reconstruction.

Background: Risk prediction of anastomotic leakage using anatomical and vascular factors has not been well established. This study aimed to assess the anatomical and vascular factors affecting the hemodynamics of the gastric conduit and develop a novel risk stratification system in patients undergoing esophagectomy with retrosternal reconstruction. Methods: This retrospective cohort study analyzed 202 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube retrosternal reconstruction between January 2008 and December 2020. Risk factors for anastomotic leakage (AL), including the anatomical index (AI) and anastomotic viability index (AVI), were evaluated using a logistic regression model. Results: According to the logistic regression model, the independent risk factors for AL were preoperative body mass index ≥23.6 kg/m2 (odds ratio [OR], 7.97; 95% confidence interval [CI], 2.44-26.00; P < 0.01), AI <1.4 (OR, 23.90; 95% CI, 5.02-114.00; P < 0.01), and AVI <0.62 (OR, 8.02; 95% CI, 2.57-25.00; P < 0.01). The patients were stratified into four AL risk groups using AI and AVI as follows: low-risk group (AI ≥1.4, AVI ≥0.62 [2/99, 2.0%]), intermediate low-risk group (AI ≥1.4, AVI <0.62 [2/29, 6.9%]), intermediate high-risk group (AI <1.4, AVI ≥0.62 [8/53, 15.1%]), and high-risk group (AI <1.4, AVI <0.62 [11/21, 52.4%]). Conclusion: The combination of AI and AVI strongly predicted AL. Additionally, the use of AI and AVI enabled the stratification of the risk of AL in patients who underwent esophagectomy with retrosternal reconstruction.

Bidirectional Elongation Strategy Using Ambiphilic Radical Linchpin for Modular Access to 1,4-Dicarbonyls via Sequential Photocatalysis.

Organic molecules that can be connected to multiple substrates by sequential C-C bond formations can be utilized as linchpins in multicomponent processes. While they are useful for rapidly increasing molecular complexity, most of the reported linchpin coupling methods rely on the use of organometallic species as strong carbon nucleophiles to form C-C bonds, which narrows the functional group compatibility. Here, we describe a metal-free, radical-mediated coupling approach using a formyl-stabilized phosphonium ylide as a multifunctional linchpin under visible-light photoredox conditions. The present method uses the ambiphilic character of the phosphonium ylide, which serves as both a nucleophilic and an electrophilic carbon-centered radical source. The stepwise and controllable generation of these radical intermediates allows sequential photocatalysis involving two mechanistically distinct radical additions, both of which are initiated by the same photocatalyst in one pot with high functional group tolerance. The methodology enables a bidirectional assembly of the linchpin with two electronically differentiated alkene fragments and thus offers rapid and modular access to 1,4-dicarbonyl compounds as versatile synthetic intermediates.

Zn(II)-Dipicolylamine-Attached Amphiphilic Polythiophene for Quantitative Pattern Recognition of Oxyanions in Mixtures.

Herein, we propose a novel amphiphilic polythiophene-based chemosensor functionalized with a Zn(II)-dipicolylamine side chain (1poly ⋅ Zn) for the pattern recognition of oxyanions. Optical changes in amphiphilic 1poly ⋅ Zn can be induced by the formation of a random coil from a backbone-planarized structure upon the addition of target oxyanions, which results in blueshifts in the UV-vis absorption spectra and turn-on-type fluorescence responses. Dynamic behavior in a polythiophene wire and/or among wires could be a driving force for obtaining visible color changes, while the molecular wire effect is dominant in obtaining fluorescence sensor responses. Notably, the magnitude of optical changes in 1poly ⋅ Zn has depended on differences in properties of oxyanions, such as their binding affinity, hydrophilicity, and molecular geometry. Thus, various colorimetric and fluorescence response patterns of 1poly ⋅ Zn to oxyanions were obtained, albeit using a single chemosensor. A constructed information-rich dataset was applied to pattern recognition for the simultaneous group categorization of phosphate and carboxylate groups and the prediction of similar structural oxyanions at a different order of concentrations in their mixture solutions.

Risk factors for rectal bleeding after volumetric-modulated arc radiotherapy of prostate cancer.

Background: It is crucially important to understand the risk factors for rectal bleeding after volumetric-modulated arc radiotherapy (VMAT) for prostate cancer to prevent subsequent rectal bleeding. We assayed clinical and dosimetric data to investigate the risk factors for rectal bleeding after VMAT of prostate cancer. Materials and methods: This study included 149 patients with prostate cancer who received VMAT from February, 2012 to June, 2020. Irradiated total doses were 78 Gy/39 fractions in 33 patients (22.1%), 76 Gy/38 fractions in 89 (59.7%), 74 Gy/37 fractions in 4 (2.7%), and 72 Gy/36 fractions in 23 (15.4%). We investigated multiple clinical and dosimetric factors with reference to rectal bleeding. Results: The median observation period was 38 months. Fourteen patients (9.4%) experienced rectal bleeding: five (3.4%) were classified as Grade 2, and nine (6.0%) as Grade 1. There were significant differences between Grade ≥ 1 and Grade 0 patients in the overlap region of the planning target volume (PTV) and the rectum, the rectal V30-75, and the mean rectal dose (p < 0.05). There were significant differences between Grade 2 and Grade 0-1 patients in rectal V30-65 and mean rectal dose (p < 0.05). Conclusions: Rectal bleeding occurred, but its grades and rate of occurrence were permissible. Higher rectal doses were shown to be related to rectal bleeding, and reduction of low/intermediate and mean rectal doses will be important for preventing rectal bleeding.

Postoperative inflammatory markers predict survival in patients after McKeown esophagectomy for esophageal cancer.

BACKGROUND: Preoperative C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) are correlated with a poor prognosis of various cancers. The significance of postoperative systemic inflammation markers for prognostic stratification of patients with esophageal cancer (EC) has not been established. Therefore, this study aimed to elucidate the impact of postoperative CAR and NLR on survival in patients with EC for prognostic stratification. METHODS: A total of 235 patients who received curative esophagectomy were analyzed. A Cox proportional hazard model was performed to detect prognostic factors. RESULTS: Multivariate analysis revealed that postoperative CAR ≥ 0.05 (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.57) and NLR ≥ 3.0 (HR, 2.81; 95% CI, 1.79-4.40) were independent prognostic factors for overall survival. Meanwhile, postoperative CAR ≥ 0.05 (HR, 1.61; 95% CI, 1.07-2.41) and NLR ≥ 3.0 (HR, 1.92; 95% CI, 1.29-2.85) were also significant prognostic factors for relapse-free survival. In addition, the patient group with postoperative CAR ≥ 0.05 and NLR ≥ 3.0 had the worst survival. CONCLUSIONS: Postoperative CAR ≥ 0.05 and NLR ≥ 3.0 can predict the poor survival of patients who received curative esophagectomy for EC.

The histone demethylase Utx controls CD8+ T-cell-dependent antitumor immunity via epigenetic regulation of the effector function.

CD8+ T cells play a central role in antitumor immune responses. Epigenetic gene regulation is essential to acquire the effector function of CD8+ T cells. However, the role of Utx, a demethylase of histone H3K27, in antitumor immunity remains unclear. In this study, we examined the roles of Utx in effector CD8+ T-cell differentiation and the antitumor immune response. In a murine tumor-bearing model, an increased tumor size and decreased survival rate were observed in T-cell-specific Utx KO (Utx KO) mice compared with wild-type (WT) mice. The number of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) was significantly decreased in Utx KO mice. We found that the acquisition of effector function was delayed and attenuated in Utx KO CD8+ T cells. RNA sequencing revealed that the expression of effector signature genes was decreased in Utx KO effector CD8+ T cells, while the expression of naïve or memory signature genes was increased. Furthermore, the expression of Cxcr3, which is required for the migration of effector CD8+ T cells to tumor sites, was substantially decreased in Utx KO CD8+ T cells. These findings suggest that Utx promotes CD8+ T-cell-dependent antitumor immune responses partially through epigenetic regulation of the effector function.

Microscopic venous invasion is a predictor of prognosis in patients with esophageal squamous cell carcinoma undergoing ineffective neoadjuvant chemotherapy and surgery.

BACKGROUND: Neoadjuvant chemotherapy followed by surgery is Japan's most effective treatment modality for advanced thoracic esophageal squamous cell carcinoma. However, the prognosis is not as expected. This study aimed to examine prognostic factors in patients with pathologically ineffective neoadjuvant chemotherapy followed by surgery for esophageal squamous cell carcinoma. METHODS: We retrospectively analyzed patients who underwent neoadjuvant chemotherapy followed by curative esophagectomy for esophageal squamous cell carcinoma between December 2008 and July 2021. The patients were divided into the neoadjuvant chemotherapy effective group and the neoadjuvant chemotherapy ineffective group according to the pathological diagnosis. Clinicopathological data, prognosis, and recurrence were analyzed. RESULTS: A total of 143 patients (121 males, 22 females; median age, 67 years) were included in this study. Of these, 34 patients were classified into the effective group and the remaining 109 patients were assigned to the ineffective group. The ineffective group had significantly worse overall survival and recurrence-free survival than the effective group (p = 0.0192 and p = 0.0070, respectively). In the ineffective group, multivariate analysis demonstrated that microscopic venous invasion was an independent prognostic factor for overall survival (hazard ratio 2.44; 95% confidence interval 1.13-5.30) and recurrence-free survival (hazard ratio 2.43; 95% confidence interval 1.24-4.73). CONCLUSIONS: Microscopic venous invasion was associated with poor survival and cancer recurrence in the neoadjuvant chemotherapy ineffective group of patients who underwent esophagectomy for esophageal squamous cell carcinoma.

[Coagulative complete remission following early gastric cancer resection in a patient with steroid-resistant acquired hemophilia A and nephrotic syndrome].

During laparoscopic cholecystectomy, an 89-year-old man was discovered to have a prolonged APTT. He was transferred to our hospital for a thorough examination because wound bleeding necessitated a reoperation. Based on coagulation factor VIII activity (FVIII:C) of 3.6% and FVIII inhibitor levels of 48.5 BU/ml, he was diagnosed with acquired hemophilia A (AHA). Due to concerns about his advanced age and postoperative infection, immunosuppressive therapy with prednisolone 0.5 mg/kg/day was initiated. His clinical course was favorable, except hemorrhagic shock caused by intramuscular hemorrhage on the right back, although low FVIII inhibitor levels persisted for more than a month; additionally, lower leg edema and increased urinary protein were also observed. He was diagnosed as with AHA and secondary nephrotic syndrome, possibly because of early gastric cancer. As a result, radical endoscopic submucosal dissection (ESD) was performed while a recombinant coagulation factor VIIa preparation was administered. AHA improved rapidly following ESD, and coagulative remission was achieved. Simultaneously, the nephrotic syndrome improved. Because the control of malignant tumors may improve the status of AHA, the timing of malignant tumor intervention must be considered considering the risk of bleeding and infection associated with immunosuppression.

["Borono-lectin"-mediated Crosstalk and Its Application to Bioengineering].

Boronic acids are able to reversibly interact with the diol groups, a commonly found motif in biomolecules including sugars, ribose and catechols. For their carbohydrate-binding properties, they can be regarded as a synthetic mimic of lectins and often termed as "borono-lectins." Importantly, the borono-lectins platform can be chemically tailored to manifest a broad profile of binding strength and specificity. Besides the structural versatility, some derivatives can undergo a sharp inversion in the state of hydration in synchronization with the molecular recognitions. This feature, when combined with amphiphilic polymeric backbones, translates into many creative principles for fine-tuning or switching the hydration and more complex molecular assemblies in a way interactive with biology. Here we provide a brief overview of our recent efforts on the related applications with special focuses on smart insulin delivery systems and sialic acid detections relevant to cancer diagnosis and treatment among others.

Lambert-Eaton myasthenic syndrome with primary thymic marginal zone B-cell lymphoma: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune paraneoplastic syndrome with proximal muscle weakness, that often complicates small cell lung cancer. It is known that neurological symptoms do not improve with malignancy treatment alone in many LEMS patients, therefore treatment is often difficult. Since Lambert-Eaton myasthenic syndrome is a rare disease with a frequency of about 1/100 that of myasthenia gravis, there are only a few case reports on malignancy complications other than small cell lung cancer. We report a LEMS patient in his 40s who was found to have an anterior mediastinal mass. We performed surgical resection and confirmed the diagnosis of primary thymic marginal zone B-cell lymphoma by pathological diagnosis using immunostaining. Thymectomy and malignant lymphoma treatment with rituximab had no effect on neurological symptoms. The neurological symptoms improved only after we provided comprehensive care with the haematology, neurology, and rehabilitation department.

Efficacy and Cost-effectiveness of Pegfilgrastim for Preventing Febrile Neutropenia During Docetaxel, Cisplatin, and 5-Fluorouracil Therapy for Esophageal Cancer.

BACKGROUND/AIM: The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events, such as febrile neutropenia (FN), is high. This study retrospectively examined whether pegfilgrastim treatment reduces FN development during DCF therapy. PATIENTS AND METHODS: This study evaluated 52 patients who were diagnosed with esophageal cancer and underwent DCF therapy at Jikei Daisan Hospital, Tokyo, Japan, between 2016 and 2020. They were divided into non-pegfilgrastim and pegfilgrastim-treated groups, and side-effects of chemotherapy and cost-effectiveness of pegfilgrastim were examined. RESULTS: Eighty-six cycles of DCF therapy were conducted (33 and 53 cycles, respectively). FN was observed in 20 (60.6%) and seven (13.2%) cases, respectively (p<0.001). The lowest absolute neutrophil count during chemotherapy was significantly lower in the non-pegfilgrastim group (p<0.001), and the number of days until improvement from nadir was significantly shorter in the pegfilgrastim group (9 vs. 11 days; p<0.001). No significant difference was found in the onset of grade 2 or more adverse events by Common Terminology Criteria for Adverse Events. However, renal dysfunction was significantly lower in the pegfilgrastim group (30.7% vs. 60.6%, p=0.038). Hospitalization costs were also significantly lower in this group (692,839 vs. 879,431 Japanese yen, p=0.028). CONCLUSION: This study revealed the usefulness and cost-effectiveness of pegfilgrastim in prevention of FN in patients treated with DCF.

Block catiomers with flanking hydrolyzable tyrosinate groups enhance in vivo mRNA delivery via π-π stacking-assisted micellar assembly.

Messenger RNA (mRNA) therapeutics have recently demonstrated high clinical potential with the accelerated approval of SARS-CoV-2 vaccines. To fulfill the promise of unprecedented mRNA-based treatments, the development of safe and efficient carriers is still necessary to achieve effective delivery of mRNA. Herein, we prepared mRNA-loaded nanocarriers for enhanced in vivo delivery using biocompatible block copolymers having functional amino acid moieties for tunable interaction with mRNA. The block copolymers were based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) modified with glycine (Gly), leucine (Leu) or tyrosine (Tyr) via ester bonds to generate block catiomers. Moreover, the amino acids can be gradually detached from the block copolymers after ester bond hydrolyzation, avoiding cytotoxic effects. When mixed with mRNA, the block catiomers formed narrowly distributed polymeric micelles with high stability and enhanced delivery efficiency. Particularly, the micelles based on tyrosine-modified PEG-PG (PEG-PGTyr), which formed a polyion complex (PIC) and π-π stacking with mRNA, displayed excellent stability against polyanions and promoted mRNA integrity in serum. PEG-PGTyr-based micelles also increased the cellular uptake and the endosomal escape, promoting high protein expression both in vitro and in vivo. Furthermore, the PEG-PGTyr-based micelles significantly extended the half-life of the loaded mRNA after intravenous injection. Our results highlight the potential of PEG-PGTyr-based micelles as safe and effective carriers for mRNA, expediting the rational design of polymeric materials for enhanced mRNA delivery.

A Novel Frailty Grade Combined with Cachexia Index and Osteopenia in Esophagectomy.

BACKGROUNDS: The optimal method for evaluating frailty grade in patients with cancer has not been established in patients undergoing esophagectomy for esophageal cancer. This study aimed to clarify the impact of cachexia index (CXI) and osteopenia on survival in esophagectomized patients for esophageal cancer to develop frailty grade for risk stratification of the prognosis. METHODS: A total of 239 patients who underwent esophagectomy were analyzed. CXI was calculated as follows: skeletal muscle index × serum albumin/neutrophil-to-lymphocyte ratio. Meanwhile, osteopenia was defined as below the cutoff value of bone mineral density (BMD) calculated by the receiver operating characteristic curve. We evaluated the average Hounsfield unit within a circle in the lower midvertebral core of the 11th thoracic vertebra on preoperative computed tomography as BMD. RESULTS: Multivariate analysis revealed that low CXI (Hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.25-3.04) and osteopenia (HR, 1.86; 95% CI, 1.19-2.93) were independent prognostic factors for overall survival. Meanwhile, low CXI (HR, 1.58; 95% CI, 1.06-2.34) and osteopenia (HR, 1.57; 95% CI, 1.05-2.36) were also significant prognostic factors for relapse-free survival. A frailty grade combined with CXI and osteopenia stratified into four groups by their prognosis. CONCLUSIONS: Low CXI and osteopenia predict poor survival in patients undergoing esophagectomy for esophageal cancer. Furthermore, a novel frailty grade combined with CXI and osteopenia stratified the patients into four groups according to their prognosis.

[Acquired hemophilia A that developed after BNT162b2 mRNA COVID-19 vaccination and worsened following re-vaccination].

An 86-year-old Japanese male patient visited a nearby hospital with painful swelling in his left upper and lower limbs 35 days after the second dose of the BNT162b2 mRNA coronavirus disease-2019 (COVID-19) vaccine. He was referred to our hematological department due to a prolonged activated partial thromboplastin time and was urgently admitted. He was diagnosed with acquired hemophilia A (AHA) based on factor VIII (FVIII) activity of 1.7%, FVIII inhibitor of 152.3 BU/ml, and FVIII-binding antibodies detected by enzyme-linked immunosorbent assay. Immunosuppressive therapy with prednisolone (PSL) at 0.5 mg/kg/day was started owing to the risk of infection due to old age and poor activities of daily living. Hemostasis treatment with bypass hemostatic preparations (rFVIIa preparation, FVIIa/FX) was administered for each bleeding event, such as intramuscular and knee joint bleeding, resulting in good hemostatic effects. Coagulative complete remission was achieved on day 69 with PSL treatment; however, FVIII activity decreased with PSL tapering. AHA relapse with rectus abdominis muscle hematoma was observed after the third vaccination. This is the first Japanese report of AHA after COVID-19 vaccination and the world's first case, in which the presence of anti-FVIII-binding antibodies were observed.

Additional Microvascular Anastomosis to Gastric Conduit During Esophagectomy Reduces Anastomotic Leaks: Propensity Score Weighting Study.

BACKGROUND: Impaired gastric conduit perfusion during esophagectomy and reconstruction is considered a key risk factor of anastomotic leaks. The aim of this study is to evaluate the indication and feasibility of additional microvascular anastomosis (AMA) to the gastric conduit in esophageal cancer surgery. PATIENTS AND METHODS: Patients who received an esophagectomy with gastric conduit reconstruction between July 2008 and July 2021 at a single center were reviewed. Patient characteristics, anastomotic viability index (AVI) of the gastric conduit measured with thermal imaging, and operative outcomes were analyzed using Fisher's exact test and Mann-Whitney U test. Two propensity score weighting methods (inverse probability of treatment weighting and overlap weighting) were applied to investigate whether AMA reduces anastomotic leaks. RESULTS: Of the 293 patients who underwent an esophagectomy over the study period, 26 received AMA. AVI in the AMA group was significantly lower than that in the control group (0.64 vs. 0.74, p = 0.026). Overall anastomotic leak rates were 3.8% in the AMA group and 12.4% in the control group. Using two different propensity score weighting methods, the same conclusion was obtained that AMA significantly reduced anastomotic leaks after esophagectomy (both p < 0.001). The logistic regression model for estimating probability of anastomotic leaks provided AVI criteria for AMA application and revealed that AMA significantly reduced the estimated leak rates by a maximum of 49%. CONCLUSIONS: Additional microvascular anastomosis significantly reduced anastomotic leaks after esophagectomy. The proposed AVI criteria for AMA application can help guide surgeons as to when AMA is needed.

Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.