Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma.

BACKGROUND: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. METHODS: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. RESULTS: The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. CONCLUSION: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.

Real-world outcome of patients with extensively pretreated multiple myeloma who were treated with selinexor and dexamethasone: a Korean multicenter retrospective analysis.

The outcomes of patients with myeloma after exposed to penta-classes are extremely poor. Selinexor is the first approved exportin inhibitor for those patients, but intractable toxicities may limit its use. This retrospective study evaluated the real-world efficacy and safety of selinexor plus dexamethasone (XD) and involved 48 patients with multiple myeloma, who were treated from November 2020 to October 2022. Their median age was 64 years, and the median number of prior lines of therapy was 6. The overall response rate was 25%, and the median progression-free survival (PFS) was 2.1 months (95% confidence interval (CI), 1.7-2.5). Patients on a reduced initial dose, delayed treatment, and dose reduction had better PFS. After XD treatment failure, 17 patients received subsequent therapy and had a median PFS of 2.4 months. The median overall survival was 4.6 months (95% CI, 2.3-6.9). Among the patients, 12 (25%) and 17 (35%) experienced dose reduction and delayed treatment, respectively. Our data show that the real-world efficacy of XD treatment in heavily pretreated patients was modest and that improving treatment adherence through reducing initial doses or delaying treatments may improve patient outcomes.

Imaging of Facial Nerve With 3D-DESS-WE-MRI Before Parotidectomy: Impact on Surgical Outcomes.

OBJECTIVE: The intra-parotid facial nerve (FN) can be visualized using three-dimensional double-echo steady-state water-excitation sequence magnetic resonance imaging (3D-DESS-WE-MRI). However, the clinical impact of FN imaging using 3D-DESS-WE-MRI before parotidectomy has not yet been explored. We compared the clinical outcomes of parotidectomy in patients with and without preoperative 3D-DESS-WE-MRI. MATERIALS AND METHODS: This prospective, non-randomized, single-institution study included 296 adult patients who underwent parotidectomy for parotid tumors, excluding superficial and mobile tumors. Preoperative evaluation with 3D-DESS-WE-MRI was performed in 122 patients, and not performed in 174 patients. FN visibility and tumor location relative to FN on 3D-DESS-WE-MRI were evaluated in 120 patients. Rates of FN palsy (FNP) and operation times were compared between patients with and without 3D-DESS-WE-MRI; propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to adjust for surgical and tumor factors. RESULTS: The main trunk, temporofacial branch, and cervicofacial branch of the intra-parotid FN were identified using 3D-DESS-WE-MRI in approximately 97.5% (117/120), 44.2% (53/120), and 25.0% (30/120) of cases, respectively. The tumor location relative to FN, as assessed on magnetic resonance imaging, concurred with surgical findings in 90.8% (109/120) of cases. Rates of temporary and permanent FNP did not vary between patients with and without 3D-DESS-WE-MRI according to PSM (odds ratio, 2.29 [95% confidence interval {CI} 0.64-8.25] and 2.02 [95% CI: 0.32-12.90], respectively) and IPTW (odds ratio, 1.76 [95% CI: 0.19-16.75] and 1.94 [95% CI: 0.20-18.49], respectively). Conversely, operation time for surgical identification of FN was significantly shorter with 3D-DESS-WE-MRI (median, 25 vs. 35 min for PSM and 25 vs. 30 min for IPTW, P < 0.001). CONCLUSION: Preoperative FN imaging with 3D-DESS-WE-MRI facilitated anatomical identification of FN and its relationship to the tumor during parotidectomy. This modality reduced operation time for FN identification, but did not significantly affect postoperative FNP rates.

Upper gastrointestinal tract perforation assessed by contrast-enhanced ultrasonography after oral Sonazoid administration in a stomach leakage mouse model.

PURPOSE: The purpose of this study was to elucidate whether contrast-enhanced ultrasonography (CEUS) can visualize orally administered Sonazoid leaking into the peritoneal cavity in a postoperative stomach leakage mouse model. METHODS: Adult female mice (n=33, 9-10 weeks old) were used. Preoperative CEUS was performed after delivering Sonazoid via intraperitoneal injection and the per oral route. A gastric leakage model was then generated by making a surgical incision of about 0.5 cm at the stomach wall, and CEUS with per oral Sonazoid administration was performed. A region of interest was drawn on the CEUS images and the signal intensity was quantitatively measured. Statistical analysis was performed using a mixed model to compare the signal intensity sampled from the pre-contrast images with those of the post-contrast images obtained at different time points. RESULTS: CEUS after Sonazoid intraperitoneal injection in normal mice and after oral administration in mice with gastric perforation visualized the contrast medium spreading within the liver interlobar fissures continuous to the peritoneal cavity. A quantitative analysis showed that in the mice with gastric perforation, the orally delivered Sonazoid leaking into the peritoneal cavity induced a statistically significant (P<0.05) increase in signal intensity in all CEUS images obtained 10 seconds or longer after contrast delivery. However, enhancement was not observed before gastric perforation surgery (P=0.167). CONCLUSION: CEUS with oral Sonazoid administration efficiently visualized the contrast medium spreading within the peritoneal cavity in a postoperative stomach leakage mouse model.

Pharmacokinetic/pharmacodynamic parameters of vancomycin for predicting clinical outcome of enterococcal bacteremia.

PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for Ctrough, 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 µg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean Ctrough ≥ 13.94 µg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

Development of prediction models for distinguishable cognitive trajectories in patients with amyloid positive mild cognitive impairment.

The clinical outcomes of patients with amyloid beta-positive (Aß+) mild cognitive impairment (MCI) are heterogeneous. We therefore developed prediction models for distinguishable cognitive trajectories in Aß+ participants with MCI. We included 238 Aß+ participants with MCI from the Alzheimer's Disease Neuroimaging Initiative to develop a group-based trajectory model and 63 Aß+ participants with MCI from the Samsung Medical Center for external validation. Three distinguishable classes, slow decliners (18.5%), intermediate decliners (42.9%), and fast decliners (38.7%), were identified. Intermediate decliners were associated with older age, higher AV45 standardized uptake value ratios (SUVR) and lower fluorodeoxyglucose (FDG) SUVR than slow decliners. Fast decliners were associated with older age, presence of APOE ε4, higher AV45 SUVR and lower FDG SUVR than slow decliners. Prediction models of cognitive decline showed good discrimination and calibration capabilities in the development and validation data sets. Our analysis yields novel insights into the cognitive trajectories of Aß+ patients with MCI, which will facilitate their effective stratification in Aß-targeted clinical trials.

Preoperative Helical Dynamic Enhanced Multidetector Row Computed Tomography: Can It Be a Prognostic Indicator in Early-Stage Non-small Cell Lung Cancer?

OBJECTIVE: This study aimed to investigate the prognostic significance of dynamic contrast-enhanced computed tomography in patients with stage IA non-small cell lung cancer (NSCLC). METHODS: We retrospectively enrolled 139 patients (77 men, 62 women; mean age, 59 years) with stage IA NSCLC who underwent dynamic contrast-enhanced computed tomography. Data on age, pathologic subtype, peak enhancement, and net enhancement of primary lung cancer were collected and correlated with 5-year survival. RESULTS: Peak enhancement had a significant correlation with overall survival in the univariable analysis (hazard ratio [HR], 1.18, confidence interval [CI], 1.01-1.38; P = 0.04) and in the multivariable analysis (HR, 1.19; CI, 1.01-1.39; P = 0.04). Patients with peak enhancement of 90 Hounsfield unit or higher had a significantly increased risk of death compared with patients with less enhancement after curative surgery (HR, 4.15; CI, 1.23-13.95; P = 0.02). CONCLUSIONS: Our study confirmed the prognostic significance of peak enhancement as an indicator for the overall survival of stage IA NSCLC.

Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma.

PURPOSE: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. MATERIALS AND METHODS: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. RESULTS: An ANC of 32.5/µL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/µL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. CONCLUSION: In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual's susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

Trimodality therapy for locally advanced esophageal squamous cell carcinoma: the role of volume-based PET/CT in patient management and prognostication.

PURPOSE: To evaluate the role of positron emission tomography/computed tomography (PET/CT) in predicting pathologic complete response (pCR) and identify relevant prognostic factors from clinico-imaging-pathologic features of locally advanced esophageal squamous cell carcinoma (eSCC) patients undergoing trimodality therapy. METHODS: We evaluated 275 patients with eSCCs of T3-T4aN0M0 and T1-T4aN1-N3M0 who received trimodality therapy. We correlated volume-based PET/CT parameters before and after concurrent chemoradiation therapy with pCR after surgery, clinico-imaging-pathologic features, and patient survival. RESULTS: pCR occurred in 75 (27.3%) of 275 patients, of whom 61 (80.9%) showed 5-year survival. Pre-total lesion glycolysis (pre-TLG, OR = 0.318, 95% CI 0.169 to 0.600), post-metabolic tumor volume (post-MTV, OR = 0.572, 95% CI 0.327 to 0.999), and % decrease of average standardized uptake value (% SUVavg decrease, OR = 2.976, 95% CI = 1.608 to 5.507) were significant predictors for pCR. Among them, best predictor for pCR was pre-TLG with best cutoff value of 205.67 and with AUC value of 0.591. Performance status (HR = 5.171, 95% CI 1.737 to 15.397), pathologic tumor size (HR = 1.645, 95% CI 1.351 to 2.002), pathologic N status (N1, HR = 1.572, 95% CI 1.010 to 2.446; N2, HR = 3.088, 95% CI 1.845 to 5.166), and post-metabolic tumor volume (HR = 1.506, 95% CI 1.033 to 2.195) were significant predictors of overall survival. CONCLUSION: Pre-TLG, post-MTV, and % SUVavg decrease are predictive of pCR. Additionally, several clinico-imaging-pathologic factors are significant survival predictors in locally advanced eSCC patients undergoing trimodality therapy.

Prognostic Value of Preoperative Serum Calcitonin Levels for Predicting the Recurrence of Medullary Thyroid Carcinoma.

Background: Serum calcitonin level is a useful biomarker for predicting primary tumor size, the extent of lymph node, and distant metastasis in patients with medullary thyroid carcinoma (MTC). However, the association between preoperative serum calcitonin levels and long-term oncologic outcomes has not yet been established. The aims of this study were to determine the preoperative serum calcitonin cut-off value for predicting disease recurrence and to evaluate its prognostic value. Methods: Patients with MTC (n = 169) who were treated at a tertiary referral hospital in Korea between 1995 and 2019 were enrolled. To determine the preoperative serum calcitonin cut-off value for predicting structural recurrence, the maximum of the standardized log-rank statistics of all possible cut-off values was used. Multivariable Cox regression analysis was used to determine prognostic factors for disease-free survival. Results: The overall disease-free survival rate was 75.7%. The preoperative serum calcitonin cut-off value that predicted structural recurrence was 309 pg/mL. Preoperative serum calcitonin levels of > 309 pg/mL were the strongest independent predictor of disease recurrence (hazard ratio (HR) 5.33, 95% confidence interval (85% CI) 1.67-16.96; P = 0.005). Lateral lymph node metastasis (HR 3.70, 95% CI 1.61-8.51; P = 0.002) and positive resection margins (HR 3.57, 95% CI 1.44-8.88; P = 0.006) were also significant predictors of disease recurrence. Conclusions: The preoperative serum calcitonin cut-off value is useful in clinical practice. It is also the best predictive factor for disease-free survival. Preoperative serum calcitonin levels may help determine the optimal postoperative follow-up strategy for patients with MTC.

Combined transarterial chemoembolization and radiofrequency ablation for subphrenic versus nonsubphrenic hepatocellular carcinoma: a propensity score matched study.

PURPOSE: To compare therapeutic outcomes of combined transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) treatment for small hepatocellular carcinoma (HCC) in subphrenic versus nonsubphrenic locations by propensity score matching. METHODS: This retrospective study included 293 patients with single HCC (≤ 3 cm) ineligible for ultrasound-guided RFA who received iodized oil TACE and subsequent RFA between June 2010 and January 2017. The patients were divided into two groups according to the tumor location: subphrenic (n = 99) and nonsubphrenic (n = 194). Subphrenic HCC was defined as a tumor abutting the diaphragm. Local tumor progression (LTP) and overall survival (OS) rates were compared by propensity score matching. Procedure-related complications were also assessed. RESULTS: Matching yielded 93 matched pairs of patients. In the matched cohorts, cumulative 1-, 3-, and 5-year LTP rates were 5.4%, 12.1%, and 12.1% in the subphrenic group and 1.1%, 7.5%, and 8.6% in the nonsubphrenic group, respectively, with no significant differences (p = 0.278). Corresponding OS rates were 100%, 80.2%, and 71.3% in the subphrenic group and 97.9%, 88.1%, and 75.6% in the nonsubphrenic group, respectively, with no significant differences (p = 0.308). The subphrenic location was not a significant risk factor for LTP and OS in multivariate analysis. There were no significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The therapeutic outcomes of combined TACE and RFA for small subphrenic HCC were similar to those for nonsubphrenic HCC. The combination therapy seems to be an effective and safe method in treating small subphrenic HCC.

Surgeon Volume and Long-Term Oncologic Outcomes in Patients with Medullary Thyroid Carcinoma.

BACKGROUND: Surgery is the most important curative treatment for medullary thyroid carcinoma (MTC). The relationship between surgeon volume (the number of surgeries performed) and short-term surgical outcomes, such as increased postoperative complication or costs, is well established. This study evaluated whether surgeon volume influenced long-term oncologic outcomes. METHODS: We retrospectively reviewed 246 patients diagnosed with MTC after initial thyroid surgery from 1995 to 2019. After exclusion, 194 patients were eligible for inclusion in the study. Surgeons were categorized as low/intermediate volume (fewer than 100 operations per year) or high volume (at least 100 operations per year). RESULTS: Of the 194 included patients, 60 (30.9%) developed disease recurrence, and 9 (4.6%) died of MTC during the median follow-up of 92.5 months. Having a low/intermediate-volume surgeon was associated with high disease recurrence (log-rank test, p < 0.001). After adjustment for age, sex, tumor type (sporadic versus hereditary), primary tumor size, presence of central lymph node metastasis (LNM), presence of lateral LNM, extrathyroidal extension, and positive resection margin, surgeon volume was a significant factor for disease recurrence (hazard ratio 2.28, p = 0.004); however, cancer-specific survival was not affected by surgeon volume (hazard ratio 4.16, p = 0.115). CONCLUSIONS: Surgeon volume is associated with long-term oncologic outcome. MTC patients will be able to make the best decisions for their treatment based on the results of this study.

The different central nervous system efficacy among gefitinib, erlotinib and afatinib in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer.

BACKGROUND: Brain metastasis is common in non-small cell lung cancer (NSCLC) and has an even higher incidence in epidermal growth factor receptor (EGFR)-mutant cancers. Although EGFR tyrosine kinase inhibitors (TKIs) are effective against brain metastases, it is unknown which first- or second-generation EGFR TKI is most effective. METHODS: Patients treated with first-line gefitinib, erlotinib, or afatinib for advanced EGFR-mutant NSCLC were included. The efficacy against brain metastasis was evaluated by comparing the response rates of measurable and non-irradiated brain metastases, central nervous system progression-free survival (CNS-PFS), and the cumulative incidence of CNS failure. RESULTS: Among the 559 patients who received EGFR-TKIs (gefitinib, n=299; erlotinib, n=93; afatinib, n=167), 198 had initial brain metastasis before starting EGFR-TKIs. The CNS response rates of gefitinib, erlotinib, and afatinib were 64.7%, 68.2%, and 72.9%, respectively (P=0.78). In the overall study population, irrespective of initial CNS metastasis, the median CNS-PFS was 17.3 months for gefitinib, 12.4 months for erlotinib, and 23.3 months for afatinib (P<0.001). In multivariate analysis for CNS-PFS, the hazard ratio (HR) of afatinib was 0.63 (95% CI, 0.47-0.83) compared with gefitinib or erlotinib. In the competing risk analysis for cumulative incidence of CNS failure, afatinib showed a lower cumulative incidence of CNS failure compared with gefitinib or erlotinib after adjusting for both EGFR mutation type and preexisting CNS metastases (HR 0.51, 95% CI, 0.34-0.75, P=0.0007). CONCLUSIONS: Through there are some limitation as a retrospective study, afatinib showed similar CNS response rates, superior CNS-PFS and cumulative incidence of CNS failure, compared with gefitinib or erlotinib.

Predicting the Risk of Malignancy of Lung Nodules Diagnosed as Indeterminate on Radial Endobronchial Ultrasound-Guided Biopsy.

The next diagnostic step in cases of indeterminate radial probe endobronchial ultrasound (radial EBUS)-guided biopsy results remains uncertain. This study aimed to identify risk factors for malignancy based on clinical findings, chest computed tomography (CT), and radial EBUS images, and to estimate the risk of malignancy in lung nodules that showed indeterminate radial EBUS-guided biopsy results by constructing a nomogram. This retrospective study included 157 patients with indeterminate results on an initial radial EBUS biopsy performed at the Samsung Medical Center from January 2017 to December 2018, but with a definitive final diagnosis. Medical records, chest CT, radial EBUS images, and the final diagnoses were reviewed. Patients were randomly divided into training and validation sets. Factors related to malignancy were identified through logistic regression analysis, and a nomogram was constructed using the training set and subsequently applied to the validation set. Six factors in univariable and multivariable analyses, including upper lobe location, spiculation, satellite nodules, echogenicity, presence of dots or linear arcs, and patency of vessels and bronchi predicted malignancy. A nomogram was constructed based on these predictors. The area under the curve (AUC) value of the nomogram was 0.858 using the chest CT factors, which improved to 0.952 when radial EBUS factors were added. The calibration curve showed good agreement between the actual and nomogram-predicted malignancy outcomes. The utility of radial EBUS images for revealing risk factors of malignancy was confirmed. Furthermore, our nomogram was able to predict the probability of malignancy in lung nodules with indeterminate radial EBUS-guided biopsy results.

Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer.

PURPOSE: We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications. METHODS: NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS). RESULTS: Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001). CONCLUSIONS: In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. APPROACH AND RESULTS: A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n = 713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2 years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio = 0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. CONCLUSION: Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.

Integrated evaluation of clinical, pathological and radiological prognostic factors in squamous cell carcinoma of the lung.

OBJECTIVE: Little is known about prognostic factors for lung squamous cell carcinoma (SCC). We aimed to explore radiologic and clinical factors affecting prognosis and to compare the prognosis of both central and peripheral lung SCCs. MATERIALS AND METHODS: Radiologic, clinical, and pathologic profiles of surgically confirmed SCCs from 382 patients were retrospectively reviewed. Tumor location, enhancement, necrosis, the presence of obstructive pneumonitis/atelectasis and underlying lung disease were evaluated on chest CT examination. Age, pulmonary function, tumor marker, and cancer stage were also assessed. Univariate and multivariate Cox regression analyses were performed to identify any correlation to overall survival (OS) and disease-free survival (DFS). Hazard rate estimation and competing risk analysis were done to evaluate recurrence pattern. RESULTS: The median follow-up period was 56.2 months. Tumors were located centrally in 230 patients (60.2%) and peripherally in 152 patients (39.8%). Age (p = 0.002, hazard ratio [HR] 1.03, 95% confidence interval [CI] = [1.01, 1.06]) and interstitial lung abnormalities (ILAs) (p<0.001, HR 5.41, 95% CI = [3.08, 9.52]) were associated with poor OS on multivariate analysis. ILAs also had a strong association to DFS (p<0.001, HR 4.25, 95% CI = [3.08, 9.52]). Central cancers had two peaks of local recurrence development at 15 and 60 months after surgery, and peripheral tumors showed rising curves for metastasis development at 60 months. CONCLUSIONS: CT-determined ILAs are a strong biomarker predicting poor outcome. Prognosis may not vary according to tumor location, but the two groups exhibited different recurrence patterns.

Treatment of Naïve HCC Combined with Segmental or Subsegmental Portal Vein Tumor Thrombosis: Liver Resection Versus TACE Followed by Radiotherapy.

BACKGROUND/AIM: There is no definite consensus regarding management of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). This study aimed to compare clinical outcomes according to initial treatment modality for treatment of naïve HCC combined with subsegmental (Vp1)/ segmental (Vp2) PVTT with liver resection (LR) versus trans-arterial chemoembolization (TACE) followed by radiotherapy (RT). MATERIALS AND METHODS: From our institutional registry, we enrolled 78 patients diagnosed with HCC combined with Vp1 or Vp2 PVTT and treated with LR or TACE followed by RT (TACE-RT) as a primary treatment. RESULTS: LR was more frequently applied for younger, nodular tumor morphology, or solitary tumor. Overall, LR yielded significantly better progression-free survival (PFS) (p=0.02, 41.9% vs. 15.7% at 2-years), and marginally higher overall survival (OS) (p=0.09, 75.8% vs. 61.5% at 2-years). There was an interaction effect between primary treatment and tumor morphology, and a significantly higher PFS was observed after LR in nodular morphology, in contrast with the lower PFS that was achieved after LR in infiltrative or massive morphology. CONCLUSION: Although LR yielded higher PFS than TACE-RT in HCC with Vp1 or Vp2 PVTT with similar acute complications, the difference in PFS between the LR and TACE-RT groups was significantly affected by tumor morphology.

Differentiating metastatic mucinous colorectal adenocarcinomas from simple cysts of the liver using contrast-enhanced and diffusion-weighted MRI.

OBJECTIVE:: To determine the value of contrast-enhanced and diffusion-weighted (DW) MRI for differentiating metastatic mucinous colorectal adenocarcinomas from simple cysts of the liver. METHODS:: 29 patients with 47 metastatic mucinous colorectal adenocarcinomas and/or 19 simple cysts of the liver who underwent contrast-enhanced and DW MRI were included in this retrospective study. Two radiologists assessed the MRI findings by consensus. Qualitative and quantitative analyses were conducted. Significant MRI findings on univariate and multivariate analyses were assessed, and their diagnostic performances for predicting metastatic mucinous colorectal adenocarcinomas were analyzed. RESULTS:: The presence of rim enhancement (odds ratio, 28.43; p = 0.008) and intracystic enhancement (oddsratio, 180.15; p = 0.001) were independently significant factors for predicting metastatic mucinous colorectal adenocarcinomas. The sensitivity and specificity of rim enhancement, intracystic enhancement, and their combination for detecting metastatic mucinous colorectal adenocarcinomas were 83% (39/47) and 63.2% (12/19), 87.2% (41/47) and 89.5% (17/19), and 72.3% (34/47) and 94.7% (18/19), respectively. Compared to simple cysts, metastatic mucinous colorectal adenocarcinomas showed significantly lower mean apparent diffusion coefficient (1.92 ± 0.81 vs 2.99 ± 0.75 × 10-3 mm2 s-1; p = 0.001) and lesion-to-liver apparent diffusion coefficient ratio (1.66 ± 0.75 vs 2.44 ± 0.56 × 10-3 mm2 s-1; p = 0.004) and higher mean signal intensity (400.3 ± 216.3 vs 222.4 ± 99.3; p = 0.039) and lesion-to-liver signal intensity ratio on hepatobiliary-phase images (0.58 ± 0.16 vs 0.30 ± 0.14; p < 0.001). CONCLUSION:: Contrast-enhanced and DW MRI may be helpful for differentiating metastatic mucinous colorectal adenocarcinomas from simple cysts of the liver. ADVANCES IN KNOWLEDGE:: On contrast-enhanced and DW MRI, rim and intracystic enhancement can be helpful for differentiating metastatic mucinous colorectal adenocarcinomas from simple cysts of the liver.