Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

The positive impact of smoking cessation on fracture risk in a nationwide cohort study.

Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009-2010 who had a previous health checkup 4-year prior (2005-2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807-0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917-0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture.

The Role of Pretreatment Serum Interleukin 6 in Predicting Short-Term Mortality in Patients with Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its aggressive progression and dismal survival rates, with this study highlighting elevated interleukin 6 (IL-6) levels in patients as a key marker of increased disease severity and a potential prognostic indicator. Analyzing pre-treatment serum from 77 advanced PDAC patients via ELISA, the research determined optimal cutoff values for IL-6 and the IL-6:sIL-6Rα ratio using receiver operating characteristic curve analysis, which then facilitated the division of patients into low and high IL-6 groups, showing significantly different survival outcomes. Notably, high IL-6 levels correlated with adverse features such as poorly differentiated histology, higher tumor burden, and low albumin levels, indicating a stronger likelihood of poorer prognosis. With a median follow-up of 9.28 months, patients with lower IL-6 levels experienced markedly better median overall survival and progression-free survival than those with higher levels, underscoring IL-6's role in predicting disease prognosis. Multivariate analysis further confirmed IL-6 levels, alongside older age, and elevated neutrophil-to-lymphocyte ratio, as predictors of worse outcomes, suggesting that IL-6 could be a critical biomarker for tailoring treatment strategies in advanced PDAC, warranting further investigation into its role in systemic inflammation and the tumor microenvironment.

Risk factors of adjacent-segment disease after short-segment fusion in patients with de novo degenerative lumbar scoliosis.

OBJECTIVE: Short-segment fusion (SSF) is an effective surgical option for appropriately selected patients with de novo degenerative lumbar scoliosis (DNDLS). Considering that DNDLS is frequently accompanied by multisegment degeneration and potential instability across the entire lumbar segments, it is inevitable that unhealthy segments remain after SSF, thereby increasing the potential risk of adjacent-segment disease (ASD) occurrence. Therefore, the authors aimed to identify the risk factors for ASD in patients with DNDLS who underwent SSF. METHODS: This retrospective study included 80 patients with DNDLS (Cobb angle > 10°) who underwent SSF (1 or 2 levels) between December 2010 and July 2018 with a minimum follow-up duration of 5 years. The participants were divided into two groups: ASD and non-ASD. ASD was defined as clinical ASD rather than radiographic ASD. Various patient and operative variables were compared between the groups. Global and regional radiographic parameters (preoperatively and postoperatively) were also compared between the two groups using plain radiography and MRI. Consequently, univariate and multivariate analyses were conducted to identify the risk factors for ASD occurrence. The receiver operating characteristic (ROC) curve was used to calculate the cutoff values. RESULTS: The mean ± SD age was 67.7 ± 7.2 years at the time of SSF, and there were 62 women (77.5%) enrolled in the study. Thirty patients (37.5%) were in the ASD group and 50 patients (62.5%) were in the non-ASD group. The mean time from the surgery to ASD diagnosis was 34.9 ± 28.2 months in ASD group. Thirteen patients required revision surgery at a mean time of 8.8 ± 7.0 months after ASD occurrence. Multivariate logistic regression analysis demonstrated that preoperative disc wedging angle (OR 1.806, 95% CI 1.255-2.598, p = 0.001), presence of facet tropism (defined as ≥ 10° difference between the facet joint angles of the right and left sides) (OR 5.534, 95% CI 1.528-20.040, p = 0.009), and foraminal stenosis ≥ grade 2 (OR 5.935, 95% CI 1.253-28.117, p = 0.025) were significant risk factors for ASD development. The cutoff value of the preoperative disc wedging angle was calculated to be 2.5° using the ROC curve. CONCLUSIONS: Preoperative disc wedging angle ≥ 2.5°, presence of facet tropism, and foraminal stenosis ≥ grade 2 were identified as significant risk factors for ASD development after SSF in patients with DNDLS.

Predictor of Postoperative Ambulatory Recovery in Metastatic Spinal Cord Compression with Delayed Surgical Timing and Progressive Paraplegia.

OBJECTIVE: To analyze preoperative predictors of ambulatory recovery after surgical treatment in metastatic spinal cord compression (MSCC) patients with delayed surgical timing and progressive paraplegia. METHODS: We reviewed patients with a preoperative lower-extremity motor grade of ≤3 and surgical timing ≥48 hours after the nonambulatory status. The recovery group (group R) and nonrecovery group (group NR) were classified according to ambulation assessment during follow-up. The data on patient demographics, origin of the primary tumor, pre and postoperative chemotherapy and radiation therapy, surgical procedures, Tokuhashi score, Karnofsky score, preoperative lower-extremity motor grade, and surgical timing were collected for analyzing predictors of postoperative ambulatory recovery. RESULTS: Of the 55 patients, 24 (43.6%) were group R and 31 patients were group NR. The preoperative motor grade of the lower extremities was the only predictive factor (P < 0.05). The mean hip flexor and knee extensor motor grades in group R were 2.0 ± 1.0 and 2.4 ± 1.1 respectively, while in group NR, they were 1.2 ± 1.0 and 1.3 ± 1.0. The odds ratios for failing to regain ambulatory ability were 12.6 in the knee extensor and 4.8 in the hip flexor when the motor grades 0-2 and 3 groups were compared. The rescue ratio of the preoperative hip flexor and knee extensor motor grade 0-2 group were 34.1% and 21.2%, grades 3 group were 71.4% and 77.3%, respectively. CONCLUSIONS: The significant predictive factor for ambulatory recovery was the preoperative lower-extremity motor grade. The preoperative knee extensor motor grade was identified as a more important factor than hip flexor motor grade in predicting ambulatory recovery.

Latissimus dorsi myocutaneous free flap for post-sacrectomy reconstruction: Outcomes compared with gluteal muscle flap.

BACKGROUND: Excision of sacral tumor results in extensive defects and vital organ exposure, requiring soft tissue reconstruction for dead space obliteration. Diverse reconstruction options, mainly regional flaps, have been utilized but are limited by high postoperative morbidity. A reliable reconstructive method with low morbidity and facilitated recovery has yet been sought for. In this study, we aimed to evaluate the use of free latissimus dorsi (LD) flap for post-sacrectomy defect reconstruction by comparing its outcomes with local gluteus maximus (GM) flap. METHODS: A retrospective review was conducted of all patients with sacral malignancy who underwent partial or total sacrectomy and immediate reconstruction with LD or GM flap between 2013 and 2022. Nineteen patients were analyzed, including 10 GM flaps and nine LD flaps. Postoperative outcomes were compared between the two groups. RESULTS: The average size of LD flaps was 173.8 cm2 . Seven patients developed complication in the GM group and two patients in the LD group. Complication rate at sacrectomy site was lower in the LD group (p = .003) showing complication-free sacrectomy site and two donor site seromas. The LD group resulted in shorter hospital stay (p = .033) and earlier ambulation than the GM group (p = .001). Mean follow-up period was 63 months for GM group and 17 months for LD group. Three patients in the GM group underwent re-operation, while no delayed complication was observed in the LD group. CONCLUSION: Free LD flaps may provide reliable outcomes with early recovery and may be considered an effective option for sacrectomy defect reconstruction.

Clinical Significance of Lordosis Orientation on Proximal Junctional Kyphosis Development in Long-Segment Fusion Surgery for Adult Spinal Deformity.

OBJECTIVE: We sought to evaluate the clinical impact of lordosis orientation (LO) on proximal junctional kyphosis (PJK) development in adult spinal deformity surgery. METHODS: This study included 152 patients who underwent low thoracic (T9-T12) to pelvis fusion and were followed up for ≥2 years. In the literature, 6 radiographic parameters representing LO were introduced, such as uppermost instrumented vertebra (UIV) slope, UIV inclination, UIV-femoral angle (UIVFA), thoracolumbar tilt, thoracolumbar slope, and lordosis tilt. Various clinical and radiographic factors including 6 LO parameters were investigated using logistic regression analysis to identify risk factors for PJK. RESULTS: The mean age was 69.4 years, and 136 patients were females (89.5%). PJK developed in 65 patients (42.8%). Multivariate logistic regression analysis revealed that only small postoperative pelvic incidence (PI)-lumbar lordosis (LL) (odds ratio [OR] = 0.962, 95% confidence interval: 0.929-0.996, P = 0.030) and large UIVFA (OR = 1.089, 95% confidence interval: 1.028-1.154, P = 0.004) were significant for PJK development. UIVFA showed significantly positive correlation with pelvic tilt (CC = 0.509), thoracic kyphosis (CC = 0.384), and lordosis distribution index (CC = 0.223). UIVFA was also negatively correlated with sagittal vertical axis (CC = -0.371). However, UIVFA did not correlate with LL, PI-LL, or T1 pelvic angle. CONCLUSIONS: LO significantly increases the risk of PJK development in ASD surgery. Multivariate analysis revealed that smaller postoperative PI-LL and greater UIVFA were significant risk factors for PJK. Surgeons should avoid undercorrection and overcorrection to prevent PJK development.

Proximal Junctional Failure after Corrective Surgery: Focusing on Elderly Patients with Severe Sagittal Imbalance.

Background: Previous reports with proximal junctional failure (PJF) included relatively young patients or deformity without sagittal imbalance. The present study focused on the two well-known risk factors for PJF, old age and severe sagittal imbalance. With these high-risk patients, the present study aimed to identify a strategy that could prevent PJF and to investigate whether the degree of correction would really affect the PJF occurrence. Methods: Patients who were ≥ 60 years of age and underwent long fusion (≥ 4) to the sacrum for severe sagittal imbalance (defined as pelvic incidence minus lumbar lordosis [PI-LL] ≥ 30°) were included. PJF was defined as a vertebral fracture at the uppermost instrumented vertebra (UIV) or UIV+1, failure of UIV fixation, myelopathy, or any need for proximal extension of fusion. Presumed risk factors were compared between the patients with and without PJF. Results: Total 146 patients (mean age, 68.4 years) with preoperative mean PI-LL of 46.8° were included. PJF developed in 39 patients (26.7%) at a mean of 18.1 months after surgery. Multivariate analysis showed that osteoporosis (odds ratio [OR], 2.812; p = 0.019) and UIV located below T10 (OR, 3.773; p = 0.010) were significant risk factors for developing PJF. However, the degree of correction did not affect PJF occurrence. Conclusions: The present study indicates that osteoporosis should be well corrected preoperatively and extending the fusion above T10 should be considered for severe imbalance in old patients. However, the amount of correction was not associated with PJF development.

Histologic subtype-based evaluation of recurrence and survival outcomes in patients with adenocarcinoma of the ampulla of Vater.

Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.

Introduction of a New Radiographic Parameter to Predict Proximal Junctional Kyphosis in Adult Spinal Deformity: UIVPTA (Uppermost Instrumented Vertebra-Pelvic Tilt Angle).

OBJECTIVE: To introduce a new sagittal parameter, uppermost instrumented vertebra-pelvic tilt angle (UIVPTA), and to determine the effects on the proximal junctional kyphosis (PJK) development in adult spinal deformity (ASD) surgery. METHODS: Patients ≥ 60 years with ASD who underwent low thoracic spine to pelvis fusion with a minimum of 2-years of follow-up were included in this study. Two groups were created according to PJK development. Various clinical and radiographic factors were compared between PJK and non-PJK groups to identify the risk factors for PJK. Cutoff value of UIVPTA for PJK development was calculated using receiver operating characteristic curve according to different pelvic incidence groups. Linear regression analysis was performed to identify factors to affect UIVPTA. RESULTS: One hundred fifity-one patients were included in this study. There were 135 female patients (89.4%). Mean age was 70.5 years. PJK developed in 65 patients (43.0%). Multivariate analysis showed that overcorrection relative to age-adjusted pelvic incidence (PI) minus lumbar lordosis (LL) (PI-LL) target and lower UIVPTA were independent risk factors for PJK. The cutoff value of UIVPTA for PJK development was calculated as 4.0° in patients with PI less than 45°, 9.5° in patients with PI between 45° and 60°, and 13.0° in patients with PI greater than 60°. Linear regression analysis showed that UIVPTA was positively affected by postoperative values of LL (coefficient = 0.505), PI-LL (coefficient = 0.674), and pelvic tilt (coefficient = 0.286). CONCLUSION: Optimal correction within the age-adjusted PI-LL combined with keeping UIVPTA within optimal range is suggested for the prevention of PJK.

Risk factors for radiographic progression of proximal junctional fracture in patients undergoing surgical treatment for adult spinal deformity.

OBJECTIVE: Proximal junctional fracture (PJFx) at the uppermost instrumented vertebra (UIV) or UIV+1 is the most common mechanism of proximal junctional failure (PJF). Few studies have assessed radiographic progression after PJFx development. Therefore, this study sought to identify the risk factors for radiographic progression of PJFx in the surgical treatment for adult spinal deformity. METHODS: In this retrospective study, among 317 patients aged > 60 years who underwent ≥ 5-level fusion from the sacrum, 76 with PJFx development were included. On the basis of the change in the proximal junctional angle (PJA), 2 groups were created: progression group (group P) (change ≥ 10°) and nonprogression group (group NP) (change < 10°). Patient, surgical, and radiographic variables were compared between the groups with univariate and multivariate analyses to demonstrate the risk factors for PJFx progression. The receiver operating characteristic (ROC) curve was used to calculate cutoff values. Clinical outcomes, such as visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) score, the Scoliosis Research Society (SRS)-22 score, and the revision rate were compared between the 2 groups. RESULTS: The mean age at index surgery was 71.1 years, and 67 women were enrolled in the study (88.2%). There were 45 patients in group P and 31 in group NP. The mean increase in PJA was 15.6° (from 23.2° to 38.8°) in group P and 3.7° (from 17.2° to 20.9°) in group NP. Clinical outcomes were significantly better in group NP than group P, including VAS-back score, ODI score, and SRS-22 scores for all items. The revision rate was significantly greater in group P than in group NP (53.3% vs 25.8%, p = 0.001). Multivariate analysis revealed that overcorrection relative to the age-adjusted ideal pelvic incidence (PI)-lumbar lordosis (LL) target at index surgery (OR 4.484, p = 0.030), PJA at the time of PJFx identification (OR 1.097, p = 0.009), and fracture at UIV (vs UIV+1) (OR 3.410, p = 0.027) were significant risk factors for PJFx progression. The cutoff value of PJA for PJFx progression was calculated as 21° by using the ROC curve. CONCLUSIONS: The risk factors for further progression of PJFx were overcorrection relative to the age-adjusted PI-LL target at index surgery, PJA > 21° at initial presentation, and fracture at the UIV level. Close monitoring is warranted for such patients in order to not miss timely revision surgery.

Mortality risk after the first occurrence of osteoporotic vertebral compression fractures in the general population: A nationwide cohort study.

Osteoporotic vertebral compression fractures (OVCF) can cause severe pain, changes in balance, gait velocity, muscle fatigue, risk of falls, and subsequent fractures. Thus, OVCF significantly lowers the individual's health-related quality of life. Additionally, OVCF may increase patient mortality rates. However, studies on post-OVCF mortality are limited. This study aimed to evaluate mortality risk after the first occurrence of OVCF in the general population using a nationwide dataset from the Korean National Health Insurance System. We identified 291,203 newly diagnosed patients with OVCF and 873,609 patients without OVCF at a ratio of 1:3 matched by sex and age between 2010 and 2012. We investigated the latent characteristics of patients' demographic information and chronic comorbidities that could affect mortality when diagnosed with OVCF. By comparing the cohort data, the hazard ratio for subsequent mortality in patients with OVCF was calculated and adjusted based on several risk factors. Despite adjusting for demographic characteristics and chronic comorbidities, the risk of mortality was 1.22 times higher in the OVCF cohort than in the control group. Multivariate analysis showed that male sex, old age, low-income status, and high Charlson Comorbidity Index were associated with a higher risk of mortality. In addition, the presence of chronic comorbidities, including diabetes mellitus, ischemic heart disease, stroke, chronic obstructive pulmonary disease, cancer, and end-stage renal disease, was shown to increase the risk of mortality. This population-based cohort study showed that newly diagnosed OVCF significantly increased the subsequent risk of mortality. Moreover, post-OVCF mortality is influenced by demographic characteristics and chronic comorbidities.

Radiographic Factors of Proximal Junctional Failure According to Age Groups in Adult Spinal Deformity.

Background: Patient age has been associated with the development of proximal junctional failure (PJF). The characteristics of adult spinal deformity (ASD) are considered different between younger and older age groups. We hypothesized that the radiographic risk factors of PJF would be different according to age groups. This study aimed to evaluate different radiographic risk factors of PJF between two age groups undergoing thoracolumbar fusion for ASD. Methods: ASD patients aged ≥ 60 years who underwent thoracolumbar fusion from the low thoracic level (T9-T12) to the sacrum were included. The minimum follow-up duration was 2 years. PJF was defined as proximal junctional angle (PJA) ≥ 20°, fixation failure, fracture, myelopathy, or necessity of revision surgery. Using various radiographic risk factors including age-adjusted ideal pelvic incidence (PI)-lumbar lordosis (LL), univariate and multivariate analyses were performed separately in two age groups: < 70 years and ≥ 70 years. Results: A total of 186 patients (90.3% women) with a mean age of 69 years were enrolled. The mean follow-up duration was 67.4 months. PJF developed in 97 patients (52.2%). There were fractures in 53 patients, PJA ≥ 20° in 26, fixation failure in 12, and myelopathy in 6. PJF developed more frequently in patients 70 years or older than in those younger than 70 years. In patients aged less than 70 years, preoperative LL, PI-LL, and a change in LL were significant risk factors in univariate analysis. Multivariate analysis showed only a change in LL was significant for PJF development (odds ratio [OR], 1.025; p = 0.021). On the other hand, in patients 70 years or older, postoperative LL, postoperative PI-LL, and overcorrection relative to the conventional PI-LL target (within ± 10°) and age-adjusted ideal PI-LL target were significant risk factors. On multivariate analysis, only overcorrection of PI-LL relative to the age-adjusted ideal target was a single significant risk factor of PJF (OR, 5.250; p = 0.024). Conclusions: In patients younger than 70 years, a greater change in LL was associated with PJF development regardless of PI-related values. However, in older patients, overcorrection of PI-LL relative to the age-adjusted PI-LL target was a significant risk factor of PJF.

Early Increase in Circulating PD-1+CD8+ T Cells Predicts Favorable Survival in Patients with Advanced Gastric Cancer Receiving Chemotherapy.

The clinical significance of PD-1 expression in circulating CD8+ T cells in patients with gastric cancer (GC) receiving chemotherapy remains unelucidated. Therefore, we aimed to examine its prognostic significance in blood samples of 68 patients with advanced GC who received platinum-based chemotherapy. The correlation between peripheral blood mononuclear cells, measured using fluorescence-activated cell sorting, was evaluated. Patients were divided into two groups according to the changes in PD-1+CD8+ T-cell frequencies between day 0 and 7. They were categorized as increased or decreased PD-1+CD8+ T-cell groups. The increased PD-1+CD8+ T-cell group showed longer progression-free survival (PFS) and overall survival (OS) than the decreased PD-1+CD8+ T-cell group (PFS: 8.7 months vs. 6.1 months, p = 0.007; OS: 20.7 months vs. 10.8 months, p = 0.003). The mean duration of response was significantly different between the groups (5.7 months vs. 2.5 months, p = 0.041). Multivariate analysis revealed that an increase in PD-1+CD8+ T-cell frequency was an independent prognostic factor. We concluded that the early increase in PD-1+CD8+ T-cell frequency is a potential predictor of favorable prognoses and durable responses in patients with advanced GC receiving chemotherapy.

Does the Amount of Correction of Sagittal Deformity Really Promote Proximal Junctional Kyphosis? Multivariate Analyses According to Uppermost Instrumented Vertebra Levels.

BACKGROUND: The present study assumed that the effects of deformity correction amounts on proximal junctional kyphosis (PJK) development after long deformity surgery would vary according to uppermost instrumented vertebrae (UIV) levels. Our study was to reveal the association between the amount of correction and PJK according to UIV levels. METHODS: Adult spinal deformity patients aged >50 years who underwent thoracolumbar fusion (≥4 levels) were included. PJK was defined by proximal junctional angles ≥15°. Presumed demographic and radiographic risk factors for PJK were evaluated including parameters regarding the correction amount such as postoperative change in lumbar lordosis and postoperative offset grouping, the value associated with age-adjusted pelvic incidence-lumbar lordosis mismatch. The patients were divided according to UIV levels of T10 or above (group A) and T11 or below (group B). Multivariate analyses were performed separately for both groups. RESULTS: The present study included 241 patients (74 for group A and 167 for group B). PJK developed in approximately half of all patients within an average of 5 years of follow-up. For group A, only body mass index (P = 0.002) was associated with PJK. No radiographic parameters were correlated. For group B, postoperative change in lumbar lordosis (P = 0.009) and offset value (P = 0.030) were significant risk factors for PJK development. CONCLUSIONS: The correction amount of sagittal deformity increased the risk of PJK only in patients with UIV at or below T11. However, it was not associated with PJK development in patients with UIV at or above T10.

Impact on Spine Surgery during the First Two Years of COVID-19 Pandemic: A Nationwide Study in South Korea.

Since December 2019, the novel coronavirus (COVID-19) has infected people worldwide. Owing to its rapid spread, elective surgeries, including spine surgery, have been re-scheduled. We analyzed nationwide data to investigate changes in the volume of spine surgery during the first two years of the pandemic. Nationwide data from January 2016 to December 2021 were obtained. We compared the total number of patients who underwent spine surgery and related medical expenses before and during the COVID-19 pandemic. In February and September, the number of patients was significantly smaller compared to January and August, respectively. Despite the pandemic, the proportion of patients undergoing spine surgery for degenerative diseases in 2021 was the highest. In contrast, the proportions of patients undergoing spine surgery for tumors showed a continuous decrease from 2019 to 2021. Although the number of spine surgeries performed at tertiary hospitals was lowest in 2020, it was not significantly smaller than that in 2019.The number of patients who underwent spine surgery in March 2020, during the first outbreak, decreased compared to the previous month, which differed from the trend observed in the pre-COVID-19 period. However, as the pandemic continues, the impact of COVID-19 on spine surgery has become less evident.

Long-term Radiographic and Clinical Outcomes After Selective Thoracic Fusion for Adolescent Idiopathic Scoliosis With Lenke 1C Curve.

BACKGROUND: Despite the promising results with selective thoracic fusion (STF) in patients with adolescent idiopathic scoliosis (AIS) of the Lenke 1C curve, postoperative coronal imbalance and progression of the unfused lumbar curve have been concerns in long-term follow-up. In this study, we aimed to investigate the radiographic and clinical outcomes after STF for AIS with Lenke 1C curve with long-term follow-up. METHODS: A total of 30 patients with AIS with Lenke 1C curves who underwent STF between 2005 and 2017 were included. Minimum follow-up duration was 5 years. Time-dependent changes in radiographic parameters were investigated preoperatively, immediately postoperatively, and at the last follow-up. In addition, radiographic adverse events such as coronal decompensation (CD), lumbar decompensation (LD), distal adding-on (DA) phenomenon, and trunk shift were evaluated at the last follow-up. The Scoliosis Research Society-22 score was used for clinical outcome evaluation. RESULTS: The mean age at the time of surgery was 13.8 years. The mean follow-up duration was 6.7 ± 0.8 years. The main thoracic curve significantly improved from 57 degrees to 23 degrees (60% correction), and the thoracolumbar/lumbar curve significantly improved from 47 degrees to 28 degrees (41% correction). Coronal balance was 15 mm after surgery but significantly improved to 10 mm at the last follow-up ( P = 0.033). At the final follow-up, 11 patients (37%) sustained at least one of the radiographic adverse events: CD in 5 patients (17%), LD in 3 (10%), DA in 4 (13%), and trunk shift in 3 (10.%). However, there were no cases requiring revision surgery. In addition, there were no significant differences in any items or total Scoliosis Research Society-22 score between the patients with and without radiographic adverse events. CONCLUSION: STF in Lenke 1C curves showed an acceptable risk of adverse radiographic events such as CD, LD, DA, and trunk shift in long-term follow-up. We suggest that STF without fusion to the thoracolumbar/lumbar curve would be sufficient in treating AIS with Lenke 1C curve. LEVEL OF EVIDENCE: Level III.

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer.

BACKGROUND: Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC. METHODS: Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model. RESULTS: The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166). CONCLUSIONS: The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma.

BACKGROUND: Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater (AoV) carcinoma is limited. AIM: To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival (DFS) rates than cases of observation following curative surgery. METHODS: We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival (OS) in patients with stage IB-III AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes. RESULTS: Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio (HR) = 2.24, P = 0.046], advanced tumor stage (HR = 1.85, P = 0.030), and vascular invasion (HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group (HR = 0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant (HR = 0.58, P = 0.098). CONCLUSION: Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.

Time-Dependent Changes in Stiffness-Related Functional Disability After Long Segmental Fusion in Elderly Patients With Adult Spinal Deformity-Minimum 2-Year Follow-up Results.

BACKGROUND: Although several studies were performed to measure stiffness-related functional disability (SRFD) after long segmental fusion for adult spinal deformity, the evaluation of SRFD was done at a single point in time. We do not know whether the disability will stay the same, worsen, or improve over time. OBJECTIVE: To evaluate the time-dependent changes of SRFD and any factors affecting these changes. METHODS: Patients who had ≥4-segment fusion with the sacrum were reviewed retrospectively. Specific Functional Disability Index (SFDI), consisting of a 12-item tool with 4 categories (sitting on the floor, sanitation activities, lower body activities, and moving activities), was used to assess the severity of SRFD. The SFDI taken at 3 months, 1 year, and 2 years postoperatively and at the last follow-up were used for evaluating the changes in SRFD. The presumed factors affecting these changes were analyzed. RESULTS: This study included 116 patients. Total SFDI scores significantly improved from 3-month to the last follow-up. Among the 4-category of SFDI, sitting on the floor showed the highest scores followed by lower body activities, sanitation activities, and moving activities at all time points. All categories except for sitting on the floor showed significant improvement from 3 months until the last follow-up. This improvement was most pronounced between 3 months and 1 year. American Society of Anaesthesiologists grade was identified as the only factor affecting time-dependent changes. CONCLUSION: SRFD was highest at 3 months, but it improved over time except for sitting on the floor. The improvement was observed greatest between 3 months and 1 year. Patients with less American Society of Anaesthesiologists grade experienced more improvement in SRFD.