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Background/Aims@#Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. @*Methods@#This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. @*Results@#This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. @*Conclusions@#In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

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Purpose@#In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT). @*Materials and Methods@#Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months. @*Results@#In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA. @*Conclusion@#Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.

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Purpose@#This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus–positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment. @*Materials and Methods@#This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT. @*Results@#With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding. @*Conclusion@#We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

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Purpose@#The safety of online contouring and planning for adaptive radiotherapy is unknown. This study aimed to evaluate the dosimetric difference of the organ-at-risk (OAR) according to the extent of contouring in stereotactic magnetic resonance image-guided adaptive RT (SMART) for pancreatic cancer. @*Materials and Methods@#We reviewed the treatment plan data used for SMART in patients with pancreatic cancer. For the online contouring and planning, OARs within 2 cm from the planning target volume (PTV) in the craniocaudal direction were re-controlled daily at the attending physician's discretion. The entire OARs were re-contoured retrospectively for data analysis. We termed the two contouring methods the Rough OAR and the Full OAR, respectively. The proportion of dose constraint violation and other dosimetric parameters was analyzed. @*Results@#Nineteen patients with 94 fractions of SMART were included in the analysis. The dose constraint was violated in 10.6% and 43.6% of the fractions in Rough OAR and Full OAR methods, respectively (p = 0.075). Patients with a large tumor, a short distance from gross tumor volume (GTV) to OAR, and a tumor in the body or tail were associated with more occult dose constraint violations—large tumor (p = 0.027), short distance from GTV to OAR (p = 0.061), tumor in body or tail (p = 0.054). No dose constraint violation occurred outside 2 cm from the PTV. @*Conclusion@#More occult dose constraint violations can be found by the Full OAR method in patients with pancreatic cancer with some clinical factors in the online re-planning for SMART. Re-contouring all the OARs would be helpful to detect occult dose constraint violations in SMART planning. Since the dosimetric profile of SMART cannot be represented by a single fraction, patient selection for the Full OAR method should be weighted between the clinical usefulness and the time and workforce required.

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Non-invasive Stratification of Hepatocellular Carcinoma Risk in Non-alcoholic Fatty Liver Using Polygenic Risk Scores

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Non-invasive Stratification of Hepatocellular Carcinoma Risk in Non-alcoholic Fatty Liver Using Polygenic Risk Scores

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Methods@#A nationwide database (2012–2016) acquired from the Korean Health Insurance Review and Assessment Service was analyzed. International disease categories in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes, medical procedure codes, and examination codes were used to identify and sort OVCF patients aged >50 years. @*Results@#There were 644,500 OVCF cases from 2012 to 2016. OVCF was most common in patients in their seventies (45%) and the number of patients increased from 117,361 in 2012 to 139,889 in 2016 (p <0.001). During 2012–2016, 8.9% of patients visited the emergency department; of those, 54.3% were hospitalized and 35% underwent magnetic resonance imaging. In OVCF treatment, bone cement augmentation rates increased from 23.4% in 2012 to 25.2% in 2016 (p <0.001), while conservative treatment rates slightly decreased from 76.5% in 2012 to 74.7% in 2016 (p <0.001). The total health insurance cost was $193,210,353.55 in 2012 and $281,968,877.65 in 2016. @*Conclusions@#The 5-year incidence of OVCF per 100,000 persons was 852.24 cases, and 45% of OVCF in South Korea occurred in patients in their seventies. The bone cement augmentation rate and total cost of OVCF are continuously increasing.

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Purpose@#This study was aim to evaluate the patterns of failure according to radiotherapy (RT) target volume for cervical lymph nodes in metastases of unknown primary origin in head and neck region (HNMUO). @*Materials and Methods@#Sixty-two patients with HNMUO between 1998 and 2016 were retrospectively reviewed. We analyzed the clinical outcomes and primary site failure depending on the radiation target volume. The target volume was classified according to whether the potential head and neck mucosal sites were included and whether the neck node was treated involved side only or bilaterally. @*Results@#Potential mucosal site RT (mucosal RT) was done to 23 patients and 39 patients did not receive mucosal RT. Mucosal RT showed no significant effect on overall survival (OS) and locoregional recurrence (LRR). The location of primary site failure encountered during follow-up period was found to be unpredictable and 75% of patients with recurrence received successful salvage therapies. No significant differences in OS and LRR were found between patients treated to unilateral (n = 35) and bilateral neck irradiation (n = 21). Treatment of both necks resulted in significantly higher mucositis. @*Conclusions@#We found no advantages in OS and LRR of patients with HNMUO when mucosal sites and bilateral neck node were included in the radiation target volume.

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PURPOSE: It is unclear whether adding concurrent chemotherapy (CT) to definitive radiotherapy (RT) following induction CT is a tolerable and cost effective treatment for non-small-cell lung cancer (NSCLC) patients aged 70 years or older with comorbidities. This study evaluated the actual clinical outcomes between concurrent chemoradiotherapy (CCRT) and RT alone following induction CT or not in patients (≥70 years) in a single institution’s clinical practice. MATERIALS AND METHODS: A total of 82 patients with unresectable stage III NSCLC between 2004 and 2016 were retrospectively analyzed. Their treatment tolerance and clinical outcomes such as overall survival (OS), locoregional recurrence (LRR), treatment toxicities and distant metastasis (DM) were evaluated. Early mortality rates were also evaluated as 4-month mortality after RT. RESULTS: Fifty-four patients received CCRT and 28 patients received RT alone. Induction CT before RT was performed for 68.5% and 50.0% in CCRT and RT alone groups. Treatment tolerance was significantly worse in CCRT (p = 0.046). The median survival was 21.1 and 18.1 months for CCRT and RT alone, which was not statistically significant. LRR and DM were also not different. Most early deaths after CCRT were attributed to non-cancer-related mortality. Acute esophagitis of grade ≥2 occurred more following CCRT (p = 0.017). In multivariate analysis, a Charlson Comorbidity Index (CCI) of ≥5 and a weight loss of ≥5% after RT were associated with poor OS. The factors adversely affecting 4-month survival were a CCI of ≥5 and CCRT. CONCLUSION: There were no significant differences in OS, LRR, and DM between CCRT and RT alone treatment in elderly patients. However, there was a poorer tolerance and higher incidence of acute esophagitis in the CCRT group. Specifically, when the patients had a CCI of ≥5, RT alone seems to be reasonable with a low probability of early death.

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BACKGROUND/AIMS: The treatment with daclatasvir plus asunaprevir (DCV+ASV) is associated with potent antiviral effects in patients with genotype 1b hepatitis C virus (HCV) infection. We investigated the real-world efficacy, changes in liver stiffness and noninvasive fibrosis markers, and the safety of DCV+ASV treatment in Korean patients. METHODS: In total, 363 patients with chronic hepatitis C were treated with DCV+ASV between August 2015 and January 2017. Finally, we analyzed the data of 270 patients who were monitored for at least 12 weeks after the end of treatment. RESULTS: The mean age was 60.7 years, and females predominated (60.4%). Most patients (64.8%) were treatment-naïve, and 56 patients (20.7%) had cirrhosis. Two hundred fifty-seven (95.2%) and 251 (93.0%) patients achieved end-of-treatment responses and sustained virological responses at 12 weeks posttreatment (SVR12), respectively. The SVR12 rates were higher in patients who were < 65 years of age, males, without cirrhosis and had lower HCV RNA levels. All LS values and fibrosis-4 and aspartate aminotransferase-to-platelet ratio index values declined from baseline to the time of assessment of SVR12. CONCLUSIONS: The DCV+ASV therapy resulted in a high SVR12 and improved liver fibrosis; the treatment was well tolerated in patients with genotype 1b HCV infections.

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PURPOSE: The aim of this study was to compare the results of the lateral entry pin technique and the crossed pin technique in treatment of Gartland type III humerus supracondylar fracture. MATERIALS AND METHODS: Seventeen patients (group I) underwent surgery using the lateral entry pin technique, and 33 patients (group II) underwent surgery using the crossed pin technique for Gartland type III humerus supracondylar fracture in Hanyang University Seoul Hospital between January 2011 and January 2014. Maintenance of reduction was compared between the 2 surgical techniques by measuring changes in Baumann angle and lateral humerocapitellar angle after surgery and after pin removal in groups I and II. In addition, the final carrying angle and level of loss of functional movement were measured for comparison of clinical results between the 2 groups. Occurrence of ulnar nerve palsy in the 2 groups was also examined. RESULTS: The mean Baumann angle and lateral humerocapitellar angle changes were 3.3degrees and 3.7 in group I and 3.1degrees and 3.4degrees in group II, respectively. No statistically significant differences were found between the 2 groups. Clinical results showed that the changes in the final carrying angle and range of motion were 2.9degrees and 2.6degrees in group I and 2.6degrees and 3.0degrees in group II, respectively, indicating no significant differences between the 2 groups. In terms of nerve damage, 1 patient in group II had temporary iatrogenic ulnar nerve palsy. CONCLUSION: The lateral entry pin technique may be regarded as an appropriate treatment that reduces the risk of iatrogenic ulnar nerve palsy and provides satisfactory results in Gartland type III humerus supracondylar fracture patients.

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Avulsion of spinous process, also called Clay-shoveler's fracture, is most prevalent among those engaged in hard physical labor. To the best of the author's knowledge, only one case of multiple spinous process fractures of the upper thoracic spine in a novice golfer has been reported. A 45-year-old female presented with intractable posterior neck pain. The patient experienced a sharp, sudden pain on the neck while swinging a golf club, immediately after the club head struck the ground. Dynamic cervical radiographic findings were C6 and C7 spinous process fractures. Magnetic resonance imaging revealed C6 and C7 spinous process fractures without spinal cord pathology. The patient was treated with pain medications and cervical bracing. The patient's pain gradually improved. The injury mechanism was speculated to be similar to Clay-shoveler's fracture. Lower cervical spinous process fractures can be associated with a golf swing. If the patient complains of long lasting neck pain and has a history of golf activity, further study should be conducted to rule out lower cervical spinous fracture.

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Osteopetrosis, a rare osteosclerotic bone disease characterized by a defect in osteoclast function and the reduced generation of superoxide by leukocytes, can be classified into several types based on their mode of inheritance, age of onset, severity, and associated clinical symptoms. Stem cell transplantation is the only curative therapy for the infantile malignant type, although alternative treatments, such as corticosteroids, calcitriol, and interferon (IFN)-gamma have been attempted in patients with milder clinical types. In addition, IFN-gamma therapy has been reported to increase bone resorption and hematopoiesis and to improve leukocyte function. Here, we present the cases of two patients with osteopetrosis who benefited from either 3 or 6 years of INF-gamma therapy that resulted in improved blood counts and no further pathological fractures.

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PURPOSE: To investigate the frequency of underlying diseases associated with respiratory distress in full-term infants, as well as its relation to the mode of delivery and clinical outcomes. METHODS: We conducted a retrospective review of 4,264 infants who had been admitted to the neonatal intensive care unit (NICU) of Chonnam University Hospital (CUH) over 5 years from January 2000 to December 2004. Full-term infants with respiratory distress such as transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), congenital pneumonia, meconium aspiration syndrome (MAS) and pneumothorax were included. We analysed the incidence of underlying disease, its relation to the mode of delivery, rate of mechanical ventilator therapy, prevalence of hypoxic ischemic encephalopathy (HIE), mortality and the length of hospitalization of surviving patients. RESULTS: Of the 4,264 patients who admitted to the NICU of CUH over the last five years, preterm infants made up 2,278 (53.4%) and full-term infants made up 1,982 (46.5%). The number of full-term patients who admitted due to respiratory distress associated with respiratory system problems excluding a congenital anomaly was 246 (12.4%). The most common underlying disease was TTN (n=161, 65.4%), and the next was RDS (n=39, 15.9 %), congenital pneumonia (n=11, 4.5%), MAS (n=7.9, 8.5%), and pneumothorax (n=14, 5.7 %). RDS was more statistically common in full-term infants born by Caesarian section (P<0.05). But there was no difference according to the mode of delivery statistically in other respiratory tract diseases. The rate of mechanical ventilator therapy was significantly higher in RDS and MAS, and the prevalence of HIE was higher in MAS (P<0.05). Mortalities of RDS and MAS were 7.7% and 9.5% each. There was no significant difference in the length of hospitalization of surviving patients. CONCLUSION: TTN was the most common respiratory tract disease in the full-term infant, and RDS was more common in the infant who was born by Cesarean section. The rates of mechanical ventilator therapy and mortality were significantly higher in the infants with RDS and MAS, and HIE was exclusively manifested by infants with MAS.

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OBJECTIVE: Development of diagnostic tools has resulted in early detection of thoracic disc herniations(TDH) even when the herniated disc is soft in consistency. In some of the cases, it is considered better not to opt for surgical treatment due to the unduly high morbidity and potential complications associated with conventional approaches. The authors have applied percutaneous endoscopic thoracic discectomy(PETD) technique to soft TDHs in order to avoid the morbidity associated with conventional approaches. METHODS: Eight consecutive patients (range, 31 to 75 years) with soft lateral or central TDH (from T2-3 to T11-12) underwent PETD between May 2001 and June 2004. The patient was positioned in a prone position with intravenous sedation and local anesthetic infiltration. The authors introduced a cannula into the thoracic intervertebral foramen using endoscopic foraminoplasty technique. Discectomy was performed with mechanical tools and a laser under continuous endoscopic visualization and fluoroscopic guidance. Functional status was assessed preoperatively and postoperatively using the Oswestry Disability Index(ODI). RESULTS: The mean ODI scores improved from 52.8 before the surgery to 25.8 at the final follow-up. In cases of myelopathy, long tract signs showed improvement. The mean operative time was 55 minutes, and no patient required conversion to open surgery. CONCLUSION: The technique allows a smaller incision and less morbidity. Soft TDH is amenable to this minimally invasive approach in selected patients with myeloradiculopathy.

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BACKGROUND AND OBJECTIVES: Time-phasic development of nitrate tolerance in cardiovascular diseases is very important because it can contribute to the advent of blunted vasodilation or rebound ischemia even during continuous NTG treatment. In such a condition, we should change the therapeutic regimen of nitrate treatment to prevent the worsening of symptoms. MATERIALS AND METHODS: We created a nitrate-tolerant rat model using an osmotic minipump, and we examined the hemodynamic response to bolus NTG infusion in vivo. We checked the phosphodiesterase (PDE) 1A1 mRNA and protein level by relative quantitative RT-PCR and western blot analysis. We used 8-cpt-cGMP for investigating the development of a time-phasic nitrate tolerance mechanism after nitrate infusion. RESULTS: NTG-treated rats revealed a significant decrease in NTG-induced MAP drop (nitrate tolerance) from 1-day and this continued to the third day. The mRNA and protein levels of PDE1A1 similarly increased during these periods. CONCLUSION: This study revealed the development of time-phasic nitrate tolerance from the the aspects of in vivo hemodynamic responses and PDE 1A1 gene expression, and our work supports the need for further investigation to come up with a different therapeutic strategy and new drugs.

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OBJECTIVE: The purpose of the current study is to investigate the effect of the prosthetic disc nucleus replacement on the mobility and height of the intervertebral disc and adjacent segments. METHODS: Thirteen patients who underwent L4-L5 prosthetic disc nucleus replacement were included in this study. A retrospective review of clinical and radiological data was conducted. The L4-L5 disc height and sagittal rotation angle of L3-L4, L4-L5, L5-S1 were measured in the static and dynamic lateral radiographs pre- and postoperatively. RESULTS: There were seven men and six women whose mean age was 37 years(range, 24-49 years). The mean follow-up period was nine months(range, 6-14 months). In all cases the L4-L5 motion segment demonstrated angular motion between flexion and extension with a mean of 4degrees(+/-2.3degrees) of sagittal rotation angle. The disc height increased from preoperative levels by 117%. There was no difference in angular motion of adjacent segments between pre- and postoperative data. CONCLUSION: The prosthetic disc nucleus replacement after discectomy is shown to restore the disc height and maintain segmental mobility.

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OBJECTIVE: The purpose of this study is to assess the survival and prognostic factors of surgically treated metastatic spine tumors. METHODS: A retrospective review of 68 patients who underwent the surgical treatment of metastatic spine tumors from 1988 to 2001 was conducted. The survival of each patient was confirmed on Feb 2002. The survival rates were calculated and several variables were examined for prognostic factors. RESULTS: Postoperative mean survival time was 21.1 months. Three month and 2 year cumulative survival was 70.3% and 21.4%, respectively. The patients who survived less than 3 months after operation were 23(33.8%). The significant prognostic factors were the category of primary tumors, postoperative ambulation, preoperative functional status, and the interval between initial diagnosis and spine metastasis. CONCLUSION: The postoperative survival was related with the biologic behavior of primary tumor and general physical condition. High mortality rate in postoperative three months suggests that more sophisticated selection criterion is needed.

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The authors report a case of intramedullary ependymal cyst at the level of conus medullares in 44-year-old man. The patient was admitted to our hospital due to progressing both lower extremities weakness and radiating pain for 6months. Magnetic resonance(MR) imaging showed intramedullary cystic mass at the level of conus which compressed spinal cord. The patient underwent partial removal and made cyst to communicate with subarachnoid space. The histologic finding was ependymal cell cyst. After surgery the patient had symptomatic improvement and in follow-up MR image cyst regressed in size.

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BACKGROUND AND OBJECTIVES: Angiotensin II (Ang II) opposes the actions of nitric oxide (NO). A balance between Ang II and NO is critical for the maintenance of normal vessel tone, and is dependent on the intracellular cGMP level. We examined the effect of Ang II treatment on cGMP-hydrolyzing phosphodiesterases (PDEs), such as PDE1 and PDE5, the two major cGMP-hydrolyzing PDEs present in rat aortic vascular smooth muscle cells (VSMCs). We also investigated whether the Ang II signaling pathway affects the expression of the cGMP-hydrolyzing PDEs gene. MATERIALS AND MEDHODS: VSMCs from Sprague-Dawley rats were incubated. Relative quantitative RT-PCR was performed for quantitation of PDE1A1, PDE5A1 mRNA expression a following in vitro Ang II treatment, and also done after pretreatment with inhibitors of the Ang II type1 (AT1) receptor, protein kinase C (PKC), mitogen activated protein kinase kinase (MEK) 1/2 and janus kinase 2 (JAK2) to investigate the effect of the Ang II signaling pathway on PDE1A1, PDE5A1 gene expression. Western blot analyses were performed to evaluate the changes of PDE1A1 and PDE5A1 protein level following treatment with Ang II. RESULTS: Ang II (400 nM) increased the PDE1A1 and the PDE5A1 mRNA expression by 2.4 and 2.3-fold, respectively, 1 hour after treatment. Ang II also increased the protein level 2 hours after treatment. Inductions of PDE1A1 and PDE5A1 mRNA were blocked by the AT1 receptor inhibitors, PKC, MEK 1/2 and JAK2. CONCLUSION: In vitro Ang II treatment upregulates the PDE1A1, PDE5A1 gene expressions and the protein levels. The PKC, MEK1/2 and JAK2 signaling pathways were essential for the Ang II-mediated PDEs gene regulation. These findings may suggest that Ang II antagonizes NO actions through the upregulation of cGMP-hydrolyzing PDEs gene expressions.

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