Quantitative assessment of breast volume changes after whole-breast irradiation for breast cancer using breast auto-segmentation.

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.

Lactoferrin-derived chimeric peptide (LFch) strongly boosts TGFß1-mediated inducible Treg differentiation possibly through downregulating TCR/CD28 signalling.

We recently reported that lactoferrin (LF) induces Foxp3+ Treg differentiation through binding to TGFß receptor III (TßRIII), and this activity was further enhanced by TGFß1. Generally, a low T-cell receptor (TCR) signal strength is favourable for Foxp3+ Treg differentiation. In the present study, we explored the effect of lactoferrin chimera (LFch, containing lactoferricin [aa 17-30] and lactoferrampin [aa 265-284]), along with TGFß1 on Foxp3+ Treg differentiation. LFch alone did not induce Foxp3 expression, yet LFch dramatically enhanced TGFß1-induced Foxp3 expression. LFch had little effect on the phosphorylation of Smad3, a canonical transcriptional factor of TGFß1. Instead, LFch attenuated the phosphorylation of S6 (a target of mTOR), IκB and PI3K. These activities of LFch were completely abrogated by pretreatment of LFch with soluble TGFß1 receptor III (sTßRIII). Consistent with this, the activity of LFch on TGFß1-induced Foxp3 expression was also abrogated by treatment with sTßRIII. Finally, the TGFß1/LFch-induced T cell population substantially suppressed the proliferation of responder CD4+ T cells. These results indicate that LFch robustly enhances TGFß1-induced Foxp3+ Treg differentiation by diminishing TCR/CD28 signal intensity.

Lactoferrin Potentiates Inducible Regulatory T Cell Differentiation through TGF-ß Receptor III Binding and Activation of Membrane-Bound TGF-ß.

Lactoferrin (LF) is known to possess anti-inflammatory activity, although its mechanisms of action are not well-understood. The present study asked whether LF affects the commitment of inducible regulatory T cells (Tregs). LF substantially promoted Foxp3 expression by mouse activated CD4+T cells, and this activity was further enhanced by TGF-ß1. Interestingly, blocking TGF-ß with anti-TGF-ß Ab completely abolished LF-induced Foxp3 expression. However, no significant amount of soluble TGF-ß was released by LF-stimulated T cells, suggesting that membrane TGF-ß (mTGF-ß) is associated. Subsequently, it was found that LF binds to TGF-ß receptor III, which induces reactive oxygen species production and diminishes the expression of mTGF-ß-bound latency-associated peptide, leading to the activation of mTGF-ß. It was followed by phosphorylation of Smad3 and enhanced Foxp3 expression. These results suggest that LF induces Foxp3+ Tregs through TGF-ß receptor III/reactive oxygen species-mediated mTGF-ß activation, triggering canonical Smad3-dependent signaling. Finally, we found that the suppressive activity of LF-induced Tregs is facilitated mainly by CD39/CD73-induced adenosine generation and that this suppressor activity alleviates inflammatory bowel disease.

Immediate breast reconstruction has no impact on the oncologic outcomes of patients treated with post-mastectomy radiation therapy: a comparative analysis based on propensity score matching.

PURPOSE: To investigate the impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM). METHODS: After a retrospective review of patients treated with PMRT between 2008 and 2017, we included 153 patients who underwent iBR and 872 patients who did not undergo iBR. Among the 153 patients who underwent iBR, 34 received one-stage iBR with autologous tissue and 119 received two-stage iBR. Conventional fractionated PMRT with a total dose of 50-50.4 Gy in 25-28 fractions was performed in all patients. Propensity scores were calculated via logistic regression. RESULTS: Patients who underwent iBR were younger, had early stage disease, and had more frequent hormone receptor-positive tumor than those who did not undergo iBR. After PSM, 127 patients from each group with well-balanced characteristics were selected. With a median follow-up of 67.5 months, iBR led to better 6-year disease-free survival rates compared to no iBR before PSM (84.8% vs. 71.4%, p = 0.003); after PSM, there was no significant difference (84.8% vs. 75.5%, p = 0.130). On multivariable analysis in the matched cohort, iBR was not associated with inferior disease-free survival (hazard ratio, 0.67; p = 0.175). In the sensitivity analysis, iBR was not associated with a lower disease-free survival across all prognostic groups. The 5-year cumulative incidence of iBR failure was 15.0%. CONCLUSION: In patients with adverse pathologic factors planning to receive PMRT, iBR did not compromise oncologic outcomes. In addition, iBR can be considered in patients treated with PMRT with several clinicopathologic risk factors.

Clinically Node-Negative Parotid Gland Cancers: Prognostic Factors of Survival and Surgical Extent.

OBJECTIVE: Conservative parotidectomy is known to reduce morbidity, but has been rarely examined in patients with clinically node-negative (cN0) parotid cancers. We evaluated the clinicopathological variables influencing the outcomes of these patients and the efficacy of conservative parotidectomy. METHODS: We reviewed the clinical and pathological data of 256 patients with cN0 parotid carcinomas who underwent curative surgery at our institution. Of these, 110 and 146 underwent conservative and total parotidectomy, respectively, with 83 undergoing elective neck dissection and 135 receiving postoperative radiotherapy. Univariate and multivariate analyses of variables predicting recurrence-free survival (RFS) and overall survival (OS) were performed. Morbidity, survival, and recurrence rates were compared between the conservative and total parotidectomy groups. RESULTS: The 5-year RFS and OS rates in all patients were 85.7 and 91.4%, respectively. Multivariate analysis showed that advanced T classification, positive resection margin, and high-histologic grade were independent prognostic factors for both RFS and OS. Among the 201 patients with low- or intermediate-grade parotid cancers, those who underwent total parotidectomy had a greater chance of facial nerve paralysis than those who underwent conservative parotidectomy (p < 0.001). The 5-year RFS and OS after conservative parotidectomy (93.7 and 100%, respectively) were not worse than those after total parotidectomy (85.5 and 90.9%, respectively). CONCLUSION: Patients with cN0 parotid cancers may be stratified by histological grade and T classification. Conservative parotidectomy may be suitable for early T1-2 low- or intermediate-grade tumors if a resection margin is secured.

Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer's disease evaluated by ß-amyloid positron emission tomography imaging.

OBJECTIVE: We evaluated the effects of bone marrow-derived mesenchymal stem cells in a model of Alzheimer's disease using serial [18F]Florbetaben positron emission tomography. METHODS: 3xTg Alzheimer's disease mice were treated with intravenously injected bone marrow-derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and ß-amyloid-reactive cells. RESULTS: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow-derived mesenchymal stem cells-treated group (n = 28). In contrast, there was no change in the ratio in control mice (n = 25) at any time point. In addition, mice that received bone marrow-derived mesenchymal stem cell therapy also exhibited significantly better memory function and less ß-amyloid-immunopositive plaques compared to controls. CONCLUSION: The therapeutic effect of intravenously injected bone marrow-derived mesenchymal stem cells in a mouse model of Alzheimer's disease was confirmed by ß-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.

Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.

Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague-Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, and ALA administration 24 h or 30 min prior to irradiation. The neck area, including SGs, was irradiated evenly at 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator. The rats were sacrificed at 2, 6, 8, and 12 weeks after irradiation. Radiation decreased SG weight, saliva secretion, AQP5 expression, parasympathetic innervation (GFRα2 and AchE expression), regeneration potentials (Shh and Ptch expression), salivary trophic factor levels (brain-derived neurotrophic factor and neurturin), and stem cell expression (Sca-1). These features were restored by treatment with ALA. This study demonstrated that ALA can rescue radiation-induced hyposalivation by preserving parasympathetic innervation and regenerative potentials.

High-flow Nasal Cannula-induced Tension Pneumocephalus.

High-flow nasal cannula (HFNC) therapy has been established as a promising oxygen treatment with various advantages for respiratory mechanics. One of the main mechanisms is to provide positive airway pressure. This effect could reduce lung injury and improve oxygenation; conversely, it may cause a complication of positive pressure ventilation. However, data are scarce regarding the possible adverse effects, particularly in adults. We report a patient who developed HFNC-induced tension pneumocephalus from an unrecognized skull base fracture. Physicians should be cautious when applying HFNC to patients with suspected skull base or paranasal sinus fracture, especially when applying a higher flow rate. HOW TO CITE THIS ARTICLE: Chang Y, Kim T-G, Chung S-Y. High-flow Nasal Cannula-induced Tension Pneumocephalus. Indian J Crit Care Med 2020;24(7):592-595.

Survival Outcome of Intermediate-Grade Salivary Gland Carcinoma.

OBJECTIVE: Histological grade is the most important factor for defining treatment strategies and predicting prognosis for salivary gland carcinoma (SGC). We examined factors affecting long-term recurrence and survival among intermediate-grade SGC (IGSGC) patients to define optimal treatment modalities and outcomes. METHODS: We reviewed the clinical and pathological data on 108 IGSGC patients who underwent definitive surgery with or without postoperative radiotherapy. We compared treatment outcomes by treatment strategies such as surgical extent for the primary tumor, neck dissection, or postoperative radiotherapy. RESULTS: During a 103-month median follow-up, local, regional, and distant recurrences were detected in 14 (13.0%), 3 (2.8%), and 21 (19.4%) patients, respectively. The 10-year locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 83.1, 76.0, and 80.1%, respectively. Multivariate analyses identified a nonparotid primary site as an independent prognostic factor for LRC (p = 0.018). Adenoid cystic carcinoma and a positive pN classification were significantly unfavorable prognostic factors for DMFS (p = 0.025 and p = 0.030, respectively); overall advanced stage was an independent prognostic factor for OS (p = 0.020). Surgical extent, elective neck dissection, and postoperative adjuvant radiotherapy did not significantly affect treatment outcomes. CONCLUSION: Patients with early-stage IGSGC of parotid origin can achieve favorable treatment outcomes with conservative surgery alone.

Research on Thermal Conductivity of Electrospun Polyacrilonitrile-Multi-Walled Carbon Nanotubes Composite Carbon Nanofiber Papers.

In recent decades, the rapid development of nanoscience and nanotechnology has accelerated materials with high thermal conductivity, such as composite carbon nanomaterials, since heat removal has become a crucial issue. In this work polyacrilonitrile (PAN) incorporated with alteration of mass fraction (0.3 wt%, 0.62 wt%, 0.92 wt%, 2.74 wt%) of the multi-walled carbon nanotubes (MWCNTs) were used to fabricate composite fibers via electrospinning. The stabilizing and carbonization reactions of composite nanofibers are conducted in tube furnace at 280 °C and 1000 °C. The structural features of flexible composite carbon nanofiber papers were characterized under scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and Raman spectroscopy. Special attention of composite carbon nanofiber papers is given to cross-plane thermal conductivity and in-plane thermal conductivity and were measured via Flash Line Analyzer. The results proved that flexible composite carbon nanofiber papers are promising heat sink radiator for a variety of applications including flexible optical and electronic devices.

Efficacy and safety of compound tri-metal stent placement for malignant perihilar biliary obstruction.

BACKGROUND: Despite many attempts to improve the patency rate of biliary stents in patients with inoperable perihilar cholangiocarcinomas, the longevity of these stents has not been satisfactory. The purpose of the present study is to report technical outcomes and clinical efficacy of the placement of compound tri-metal stent in patients with malignant perihilar biliary obstruction. MATERIALS AND METHODS: Retrospective analysis was performed of the medical records of 26 consecutive patients with inoperable malignant perihilar biliary obstruction who underwent compound tri-metal stent placement through a percutaneous transhepatic biliary drainage tube from January 2012 to April 2017. RESULTS: Placement of the compound tri-metal stent was successfully completed in all 26 patients (technical success, 100%). There was neither procedure-related mortality nor 30-day mortality. None of these patients underwent additional metallic stent placement within 60 days secondary to recurrent cholangitis or stent occlusion. Successful drainage was achieved in 25 (96.2%) of 26 patients who received a compound tri-metal stent. Patients treated with compound tri-metal stent placement had a median stent patency of 145 days (range, 24-426 weeks) and a median survival time of 188 days (range, 37-1732 days). CONCLUSIONS: Placement of compound tri-metal stent in patients with malignant perihilar biliary obstruction may offer a safe and effective alternate technique to improve biliary drainage and stent patency.

Immediate Effects of Sports Taping Applied on the Lead Knee of Low- and High-Handicapped Golfers During Golf Swing.

Kim, T-G, Kim, E-K, and Park, J-C. Immediate effects of sports taping applied on the lead knee of low- and high-handicapped golfers during golf swing. J Strength Cond Res 31(4): 981-989, 2017-Elite golf athletes suffer from various musculoskeletal injuries due to repeated golf swings. Repetitive varus moment during golf swing has been suggested as a possible cause of injuries to the lead knee. The aim of this study was to objectively and quantitatively evaluate the immediate effects of sports taping on the lead knee of elite golfers to restrict varus moment. Thirty-one elite golfers were assigned to the low- (LHG, n = 15) or high-handicapped group (HHG, n = 16). Using 3-dimensional motion analysis, the lead knee position on the frontal plane with and without rigid taping (RT), elastic taping (ET), and placebo taping was identified in 4 separate phases by the 5 events of golf swing as follows: the peak of the backswing (E1), parallel to the ground during downswing (E2), ball impact (E3), parallel to the ground during follow-through (E4), and finish (E5). The LHG when using a driver club had decreased movement toward knee varus with RT and ET than that without it from E1 to E2 (p = 0.001). The LHG when using a 5-iron club decreased movement toward knee varus with RT than that without it from E1 to E2 (p = 0.006) and from E2 to E3 (p = 0.019). The HHG when using a driver club had decreased movement toward knee varus with RT from E1 to E2 (p = 0.014). Sports taping may be helpful for elite golfers in terms of reducing varus moment of the lead knee during the downswing and be useful for the development of preventive strategies for golf-related knee injuries.

Toll-like receptor 2 gene polymorphisms in Korean women with human papillomavirus-related cervical neoplasia.

INTRODUCTION: The aim of this study was to investigate the association between Toll-like receptor 2 (TLR2) gene polymorphisms and human papillomavirus (HPV)-related cervical neoplasia in Korean women. MATERIAL AND METHODS: Peripheral blood samples collected from 127 patients with HPV-related cervical neoplasia and 175 healthy women were genotyped for the TLR2 -16934, +1350, intron1, and 3' untranslated region (UTR) polymorphisms using the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: The TLR2 -16934 A/A, intron1 A/A, and +1350 T/C genotypes were more frequent in patients than in controls [odds ratio (OR) = 2.1, 95% CI = 1.302-3.475, p = 0.002; OR = 1.9, 95% CI = 1.168-3.169, p = 0.010; and OR = 1.9, 95% CI = 1.211-3.123, p = 0.006, respectively]. The frequencies of the TLR2 + 1350 C and 3'UTR G alleles were also higher in patients (OR = 2.0, 95% CI = 1.236-3.121, p = 0.004 and OR = 1.7, 95% CI = 1.005-3.076, p = 0.046, respectively). The genotype frequencies of TLR2 -16934 A/A and intron1 A/A increased with increasing oncogenic risk of the HPV genotype, as follows. low-risk type < high-risk type < HPV-16 and/or HPV-18 type (p = 0.008). CONCLUSIONS: Our study provides the first evidence that TLR2 gene polymorphisms are associated with high-risk type HPV-related cervical neoplasia and may play an important role in susceptibility to HPV infection. Further large-scale and functional studies are needed to confirm the role of TLR2 gene polymorphisms in HPV-related cervical neoplasia.

Characteristic Study of Boron Doped Carbon Nanowalls Films Deposited by Microwave Plasma Enhanced Chemical Vapor Deposition.

In this research, catalyst-free vertically aligned boron doped carbon nanowalls films were fabricated on silicon (100) substrates by MPECVD using feeding gases CH4, H2 and B2H6 (diluted with H2 to 5% vol) as precursors. The substrates were pre-seeded with nanodiamond colloid. The fabricated CNWs films were characterized by Scanning Electron Microscopy (SEM) and Raman Spectroscopy. The data obtained from SEM confirms that the CNWs films have different density and wall thickness. From Raman spectrum, a G peak around 1588 cm(-1) and a D band peak at 1362 cm(-1) were observed, which indicates a successful fabrication of CNWs films. The EDX spectrum of boron doped CNWs film shows the existence of boron and carbon. Furthermore, field emission properties of boron doped carbon nanowalls films were measured and field enhancement factor was calculated using Fowler-Nordheim plot. The result indicates that boron doped CNWs films could be potential electron emitting materials.

Thermal Conductivity of Diamond Packed Electrospun PAN-Based Carbon Fibers Incorporated with Multi Wall Carbon Nanotubes.

Multi wall carbon nanotubes (MWCNTs) and diamond are renowned as superlative material due to their relatively high thermal conductivity and hardness while comparing with any bulk materials. In this research, polyacrylonitrile (PAN) solution incorporated with MWCNTs at an alteration of mass fractions (0 wt%, 0.6 wt%, 1 wt%, 2 wt%) were fabricated via electrospinning under optimized parameters. Dried composite nanofibers were stabilized and carbonized, after which water base polytrafluorethylene (PTFE) mixed with nano diamond powder solution was spin coated on them. Scanning electron microscopy, Raman spectroscopy, X-ray scattering and Laserflash thermal conductivity were used to characterize the composite nanofiber sheets. The result shows that the thermal conductivity increased to 4.825 W/m K from 2.061 W/mK. The improvement of thermal conductivities is suggesting the incorporation of MWCNTs.

A New Double Trapezoid-Shaped Osteotomy for Reduction Malarplasty.

BACKGROUND: Various surgical techniques have been introduced and developed for the reduction of wide zygomatic bone. However, the previous methods have several disadvantages, including the following: potential cheek droop, a limited amount of possible volume reduction, an unfavorable contour due to nonunion, and limited inward repositioning of the zygomatic arch. Thus, the authors introduce an effective method to overcome the limitations and disadvantages of other previous reduction malarplasty techniques. METHODS: From March of 2010 to May of 2014, 532 women and 152 men underwent reduction malarplasty using a double trapezoid-shaped osteotomy. This method was created by making both 1 trapezoid-shaped osteotomy line that consisted of 2 oblique and 1 transverse line in the frontal view, and a second trapezoid-shaped osteotomy line, which consisted of 2 oblique osteotomies made to be slightly broader in the cross-sectional view. RESULTS: Reduction malarplasty with double trapezoid-shaped osteotomy was successfully performed in all patients. No severe complications were observed. There were some minor complications. In most patients, a wide midface with prominent malar eminences was reshaped into a slender contour. CONCLUSIONS: A double trapezoid-shaped osteotomy for reduction malarplasty might be a more effective method to overcome the limitations of other previous techniques. The prominent malar eminences can be reduced effectively without major complications, and moreover, the cheek area can be induced to have an upward lifting and a 3-dimensional convexity of the midface.

Factors associated with lateral pelvic recurrence after curative resection following neoadjuvant chemoradiotherapy in rectal cancer patients.

PURPOSE: This study aims to determine the risk factors for lateral pelvic recurrence (LPR) in rectal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and curative surgery. METHODS: Four hundred forty-three patients treated with neoadjuvant CRT and curative surgery from October 1999 through June 2009 were analyzed. All patients underwent total mesorectal resection without lateral pelvic lymph node (LPLN) dissection. Recurrence patterns and lateral pelvic recurrence-free survival (LPFS) were evaluated relative to clinicopathologic parameters including pelvic LN status. RESULTS: Median follow-up was 52 months, with locoregional recurrence in 53 patients (11.9 %). Of the 53 patients, 28 (52.8 %) developed LPR, of which eight had both central and lateral PR. Multivariate analysis showed a significant relationship between LPFS and the number of lateral pelvic LN (p = 0.010) as well as the ratio of the number of positive LN/number of dissected LN (p = 0.038). The relationship between LPFS and LPLN size had a marginal trend (p = 0.085). Logistic regression analysis showed positive relationships between LPR probability and the number of LPLN (odds ratio [OR] 1.507; 95 % confidence interval [CI] 1.177-1.929; p = 0.001) as well as LPLN size (OR 1.124; CI 1.029-1.227, p = 0.009). CONCLUSIONS: LPLN ≥ 2 and a ratio of the number of positive LN/number of dissected LN > 0.3 were prognostic of poor LPFS. The prediction curve of LPR according to the number and size of LPLN could be useful for determining the benefit of additional lateral pelvic treatment.

Combined High Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-Institutional Cohort Study.

Purpose: The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC. Materials and Methods: Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model. Results: The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30-110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified 2 risk factors, EQD2 of ≥60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors; group 1, EQD2 ≥60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 <60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p<0.05). Conclusion: Combined high dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.