Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Background: Thrombocytopenia is a condition where platelet counts are below the normal range (< 150 ×103 /µL), resulting in a higher risk of bleeding and affecting the results of hip arthroplasty. We assessed the impact of preoperative platelet counts on the clinical results of patients who underwent hip arthroplasty. Methods: Between April 2003 and March 2023, 437 patients (451 hips), who had preoperative thrombocytopenia of less than 150 ×103 /µL platelets, underwent hip arthroplasty. Preoperative platelet levels were categorized into severe thrombocytopenia (< 50 ×103 /µL) and non-severe thrombocytopenia (50–149 ×103 /µL). Total blood loss, operation time, requirement of transfusion, amount of transfusion, duration of surgical wound oozing, length of hospital stay, mortality rate at 1 year after surgery, and any complication were compared between the 2 groups. Results: No notable differences were observed in the surgery time or the total amount of blood loss between the groups. The requirement of transfusion and the amount of transfused blood were higher in the severe thrombocytopenia group. Prolonged oozing was found in around 18% in both groups, while periprosthetic joint infections occurred in 3 of the non-severe thrombocytopenia group. No significant difference was noted in the duration of hospital stay (25.6 ± 18.3 days vs. 19.4 ± 16.6 days, p = 0.067) and 1-year mortality (22.2% vs. 11.8%, p = 0.110). Conclusions Hip arthroplasties are safe for patients with low platelet counts and do not lead to prolonged hospital stays. On the other hand, patients with severe thrombocytopenia tend to need blood transfusions more frequently than those with less severe thrombocytopenia.

Background: The Arbeitsgemeinschaft für Osteosynthesefragen (AO) and the Orthopaedic Trauma Association (OTA) classification system for diaphyseal fracture has been recently revised to refine and enhance the accuracy of fracture categorization. This study aimed to investigate the interobserver reliability of the new AO/OTA classification and to compare it with the older version in femoral shaft fractures. Methods: We retrospectively analyzed 139 patients (mean age, 43.8 ± 19.5 years; 92 men and 47 women) with femoral shaft fractures who were treated from 2003 to 2017. Four well-trained observers independently classified each fracture following the previous and revised AO/OTA classification system. We calculated the Fleiss kappa for the interobserver reliability. Results: The previous classification showed the kappa value of 0.580 (95% confidence interval [CI], 0.547–0.613), and the revised version showed 0.528 (95% CI, 0.504–0.552). Both the old and the revised versions showed moderate reliability. Conclusions Our study highlights the moderate interobserver reliability of both the previous and new AO/OTA classification systems for diaphyseal femur fractures. These findings emphasize the importance of standardized systems in clinical decision-making and underscore the need for ongoing education and collaboration to enhance fracture classification.

Purpose: In total mastectomy (TM), sentinel lymph node biopsy (SLNB) is recommended but can be omitted for breast-conserving surgery (BCS) in patients with ductal carcinoma in situ (DCIS). However, concerns regarding SLNB-related complications and their impact on quality of life exist. Consequently, further research is required to evaluate the role of axillary surgeries, including SLNB, in the treatment of TM. We aimed to explore the clinicopathological factors and outcomes associated with axillary surgery in patients with a final diagnosis of pure DCIS who underwent BCS or TM. Methods: We retrospectively analyzed large-scale data from the Korean Breast Cancer Society registration database, highlighting on patients diagnosed with pure DCIS who underwent surgery and were categorized into two groups: BCS and TM. Patients were further categorized into surgery and non-surgery groups according to their axillary surgery status. The analysis compared clinicopathological factors and outcomes according to axillary surgery status between the BCS and TM groups. Results: Among 18,196 patients who underwent surgery for DCIS between 1981 and 2022, 11,872 underwent BCS and 6,324 underwent TM. Both groups leaned towards axillary surgery more frequently for large tumors. In the BCS group, clinical lymph node status was associated with axillary surgery (odds ratio, 11.101; p = 0.003). However, in the TM group, no significant differences in these factors were observed. Survival rates did not vary between groups according to axillary surgery performance. Conclusion The decision to perform axillary surgery in patients with a final diagnosis of pure DCIS does not affect the prognosis, regardless of the breast surgical method.Furthermore, regardless of the breast surgical method, axillary surgery, including SLNB, should be considered for high-risk patients, such as those with large tumors. This may reduce unnecessary axillary surgery and enhance the patients’ quality of life.

Purpose: An increasing number of older patients now undergo liver transplantation (LT). Although the overall outcomes in older patients are not different from those of younger patients, there is no tool to predict LT prognosis in older patients.We hypothesized that a modified Charlson comorbidity index (mCCI) and 5-factor modified frailty index (mFI-5) can predict outcomes in older patients after LT. Methods: This retrospective study included 155 patients (aged >65 years) who underwent LT at Seoul National University Hospital. The recipients were subcategorized into 2 groups based on the mCCI score and mFI-5: the low (0–1) and high (2–5) mCCI groups, and low (≤0.4) and high (>0.4) mFI-5 groups. The independent effect of each variable on post-LT survival was determined using the mCCI subgroup, age at transplantation, sex, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score, and mFI-5 subgroup. Results: The high-mCCI group (41 patients) showed significantly lower 1- and 3-month and 1-, 3-, and 5-year survival than the low-mCCI group. Using the Cox regression model, the mCCI, sex, and MELD score remained significant. The mFI-5 was not a significant factor to predict patients’ survival. Conclusion The mCCI and MELD scores could be used to predict post-LT survival in older patients.

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

Background: Increasing longevity has caused the very old population to become the fastest-growing segment. The number of centenarians (over 100 years old) is increasing rapidly. Fractures in the elderly lead to excessive medical costs and decreased quality of life with socioeconomic burdens. However, little research has thoroughly examined the functional outcomes and mortality of hip fractures in centenarians. Methods: This is a retrospective observational study. Sixty-eight centenarian hip fracture patients were admitted to the 10 institutions from February 2004 to December 2019. Fifty-six patients with 1-year follow-up were finally included. The following data were obtained: sex, age, body mass index, Charlson comorbidity index value on the operation day, Koval’s classification for ambulatory ability, type of fracture, the time interval from trauma to surgery, American Society of Anesthesiologists grade, surgery-related complications, and duration of hospital stay. Postoperative Koval’s classification (at 1 year after surgery) and information about death were also collected. Multivariate analysis was performed to analyze the risk factors affecting mortality 1 year after surgery. Results: Mortality rates were 26.8% at 6 months and 39.3% at 1 year. The 90-day mortality was 19.6%, and one of them (2.1%) died in the hospital. The 1-year mortality rates for the community ambulatory and non-community ambulatory groups were 29% and 52%, respectively. Only 9 (16.1%) were able to walk outdoors 1 year after surgery. The remaining 47 patients (83.9%) had to stay indoors after surgery. Multivariate analysis demonstrated that the pre-injury ambulatory level (adjusted hazard ratio, 2.884; p = 0.034) was associated with the risk of mortality. Conclusions We report a 1-year mortality rate of 39.3% in centenarian patients with hip fractures. The risk factor for mortality was the pre-injury ambulatory status. This could be an important consideration in the planning of treatment for centenarian hip fracture patients.

As the aging population increases, the number of patients with osteoporosis is gradually rising. Osteoporosis is a metabolic bone disease characterized by low bone mass and the microarchitectural deterioration of bone tissue, resulting in reduced bone strength and an increased risk of low-energy or fragility fractures. Thus, the use of anti-resorptive agents, such as bisphosphonates (BPs), to prevent osteoporotic fractures is growing annually. BPs are effective in reducing hip and other fractures. However, the longer a patient takes BPs, the higher the risk of an atypical femoral fracture (AFF). The exact mechanism by which long-term BP use affects the development of AFFs has not yet been clarified. However, several theories have been suggested to explain the pathogenesis of AFFs, such as suppressed bone remodeling, impaired bone healing, altered bone quality, and femoral morphology. The management of AFFs requires both medical and surgical approaches. BPs therapy should be discontinued immediately, and calcium and vitamin D levels should be evaluated and supplemented if insufficient. Teriparatide can be used for AFFs. Intramedullary nailing is the primary treatment for complete AFFs, and prophylactic femoral nailing is recommended if signs of an impending fracture are detected.

Objectives: This review assessed the performance of implant-supported fixed hybrid prostheses in 21 patients who received a total of 137 implants between 2003 and 2010. The implants were evaluated for marginal bone resorption, complications, success rate, and survival rate based on their vertical angularity, type of bone graft, and measured implant stability. Materials and Methods: One-way ANOVA and chi-square tests were used to analyze the relationships among long-term evaluation factors and these variables. The mean initial bone resorption in the implant group with a vertical angle of more than 20° was 0.33 mm and mean final bone resorption was 0.76 mm. In contrast, the mean initial bone resorption in the implant group with a vertical angle of less than 10° was 1.19 mm and mean final bone resorption was 2.17 mm. Results: The results showed that mean bone resorption decreased with an increase in the vertical placement angle of the implants used in fixed hybrid prostheses, as well as in the group without additional bone grafts and those with high implant stability. The success rate of implants placed after bone grafting was found to be higher than those placed simultaneously. Conclusion These results suggest that implant-supported fixed hybrid prostheses may be an effective treatment option for edentulous patients, and intentionally placing implants with high angularity may improve outcomes.