Intracorporeal anastomosis in minimally invasive right hemicolectomy: a nationwide survey of the Korean Society of Coloproctology.

Purpose: We investigated the current practices and perceptions of colorectal surgeons in South Korea regarding intracorporeal ileocolic anastomosis (IIA) in minimally invasive right hemicolectomy (RHC). Methods: Members of the Korean Society of Coloproctology (KSCP) participated in an online survey encompassing demographic information, surgical experiences, methods for IIA, and advantages, barriers, and perceptions of IIA. We performed a statistical analysis of survey results. Results: Among the 1,074 KSCP members contacted, 178 responded to the survey. Most respondents were males aged 40-49 years with >10 years of experience who were affiliated with a tertiary healthcare facility. One hundred fifty-six respondents had performed <100 colorectal cancer surgeries annually. Fifty-nine respondents reported experiences of the IIA technique in minimally invasive RHC. Most respondents favored the isoperistaltic side-to-side (S-S) anastomosis and stapled S-S anastomosis, hand-sewn closure for the common channel, and the periumbilical area for primary specimen extraction. Respondents with IIA experience emphasized the reduction in postoperative complications as the primary reason for performing IIA, whereas respondents without IIA experience cited the lack of benefits as the main deterrent. Respondents commonly cited concerns regarding anastomotic leakage and intraabdominal contamination as the primary reasons for not performing IIA. Respondents with IIA experience demonstrated a more positive response towards attempting or transitioning to IIA than those without. Respondents with IIA experience prioritized self-sufficiency, whereas respondents without IIA experience prioritized proctorship and discussions of the initial cases. Conclusion: Measures to standardize the IIA technique and appropriate training programs must be implemented to enhance its use in minimally invasive RHC.

Initial case series experience with robotic-assisted transanal minimally invasive surgery performed with da Vinci single-port system for the excision of rectal cancer.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is widely used for rectal lesion excision. Robot-assisted TA TAMIS (R-TAMIS) may improve surgical ergonomics. The introduction of the da Vinci Single-Port (SP) robot, designed for endoluminal surgery, has brought new possibilities. Our primary objective herein was to assess the technical and oncological feasibility and efficacy of Single-port robotic TAMIS (SPR-TAMIS) in rectal cancer excision. The secondary objective was to analyze the perioperative outcomes. MATERIALS AND METHODS: We included 14 consecutive patients with rectal cancer who underwent SPR-TAMIS between April 2021 and February 2023. Patient data, surgical details, and clinical outcome data were collected to assess the safety and feasibility of SPR-TAMIS. RESULTS: The median participant age was 72 years, and full-thickness excision was performed without specimen fragmentation in all cases. The median tumor diameter was 2.7 cm, positioned between 10 cm proximally and 7 cm distally from the anal verge. Negative margins were achieved in 93% of cases, with one case requiring further resection. The median operative time was 175 min, and the median hospital stay was 5 days. No intraoperative conversion from SPR-TAMIS to laparoscopic or conventional transanal excision was required. No mortalities or major postoperative complications occurred; however, one patient (7.1%) experienced minor morbidity manifesting as wound dehiscence (Clavien-Dindo grade I). No recurrence was observed during the 24-month follow-up. CONCLUSIONS: In our early experience, SPR-TAMIS is a safe and feasible surgery for selected early stage rectal cancers, offering enhanced visualization and stable maneuverability transanally. This platform may have potential advantages for the excision of larger or more proximal lesions.

Long-term survival analysis of robotic esophagectomy for esophageal cancer.

Robotic esophagectomy has improved early outcomes and enhanced the quality of lymphadenectomy for esophageal cancer surgery. This study aimed to determine risk factors for long-term survival following robotic esophagectomy and the causes of long-term mortality. We included patients who underwent robotic esophagectomy at our institute between 2010 and 2022. Robotic esophagectomy was defined as a surgical procedure performed robotically in both the abdomen and thorax. Robotic esophagectomy was performed in patients at all stages, including advanced stages, even in patients with stage IV and supraclavicular lymph node metastasis. A total of 340 patients underwent robotic esophagectomy during the study period. Ivor-Lewis operation and McKeown operation were performed on 153 (45.0%) and 187 (55.0%) patients, respectively. The five-year survival rates based on clinical stages were as follows: 85.2% in stage I, 62.0% in stage II, 54.5% in stage III, and 40.3% in stage IV. Risk factors for long-term survival included body mass index, Charlson comorbidity index, clinical stages, and postoperative complications of grade 4 or higher. Among the cases of long-term mortality, recurrence accounted for 42 patients (61.7%), while non-cancer-related death occurred in 26 patients (38.2%). The most common cause of non-cancer-related death was malnutrition and poor general condition, observed in 11 patients (16.2%). Robotic esophagectomy has demonstrated the ability to achieve acceptable long-term survival rates, even in patients with cervical lymph node metastasis. However, addressing high-grade postoperative complications and long-term malnutrition remains crucial for further improving the long-term survival outcomes of patients with esophageal cancer.

Comparison of Clinical Outcomes and Postoperative Nutritional Status Between Early and Late Oral Feeding After Esophagectomy: An Open Labeled Randomized Controlled Trial.

OBJECTIVE: To compare nutritional and postoperative outcomes between early oral feeding and late oral feeding with jejunostomy feeding support after esophagectomy. SUMMARY BACKGROUND DATA: Esophagectomy is associated with substantial body weight loss and malnutrition, impacting the prognosis of esophageal cancer patients. Despite many studies on post-esophagectomy nutritional support, optimal strategies remain elusive. This study investigates the impact of jejunostomy feeding with late oral feeding compared to conventional oral feeding on nutritional and postoperative outcomes. METHODS: We performed a single-center prospective open-labelled randomized controlled trial between 2020 and 2022. Patients aged 18 to 75 years with resectable esophageal cancer were randomly assigned to undergo either early oral feeding (early group) or late oral feeding with jejunostomy feeding support (late group) after esophagectomy. The primary endpoint was body weight loss from preoperative body weight at postoperative 4-5 weeks and 4 months. Other perioperative and nutritional outcomes were also evaluated. RESULTS: We randomly assigned 29 patients to the early group and 29 patients to the late group. The late group exhibited significantly less body weight loss at both postoperative 4-5 weeks (8.3% vs. 5.6%; P =0.002) and 4 months (15.0% vs. 10.5%; P =0.003). The total calorie intake and protein intake were higher in the late group for both postoperative 4-5 weeks (1800 kcal/day vs. 1100 kcal/day; P <0.001) and 4 months (1565 kcal/day vs. 1200 kcal/day; P =0.010). Sixty percentage of early group changed to malnutrition state, while 40% of the late group changed to malnutrition. The complication rate and length of hospital stays were similar. CONCLUSIONS: The late group demonstrated prevention of significant body weight loss, enhanced nutritional intake, and reduces malnutrition without compromising short-term surgical outcomes.

Reactive oxygen species driven prodrug-based nanoscale carriers for transformative therapies.

Reactive oxygen species (ROS) drive processes in various pathological conditions serving as an attractive target for therapeutic strategies. This review highlights the development and use of ROS-dependent prodrug-based nanoscale carriers that has transformed many biomedical applications. Incorporating prodrugs into nanoscale carriers not only improves their stability and solubility but also enables site-specific drug delivery ultimately enhancing the therapeutic effectiveness of the nanoscale carriers. We critically examine recent advances in ROS-responsive nanoparticulate platforms, encompassing liposomes, polymeric nanoparticles, and inorganic nanocarriers. These platforms facilitate precise control over drug release upon encountering elevated ROS levels at disease sites, thereby minimizing off-target effects and maximizing therapeutic efficiency. Furthermore, we investigate the potential of combination therapies in which ROS-activated prodrugs are combined with other therapeutic agents and underscore their synergistic potential for treating multifaceted diseases. This comprehensive review highlights the immense potential of ROS-dependent prodrug-based nanoparticulate systems in revolutionizing biomedical applications; such nanoparticulate systems can facilitate selective and controlled drug delivery, reduce toxicity, and improve therapeutic outcomes for ROS-associated diseases.

Pneumatosis cystoides intestinalis induced by sunitinib therapy in a patient with metastatic renal cell carcinoma: A case report.

INTRODUCTION: Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by multiple gas-filled cysts in the gastrointestinal tract and is associated with numerous conditions. Benign PCI can occur secondary to certain medications, such as anticancer-targeted therapies. Here, we report a rare case of PCI that developed following sunitinib therapy for metastatic RCC and was successfully managed with conservative treatment without surgery. PATIENT CONCERNS: A 57-year-old woman with a medical history of metastatic renal cell carcinoma (RCC) referred to the Department of General Surgery after completion of the 16th cycle of sunitinib because of abnormal findings on abdominopelvic computed tomography (CT), suggesting necrotizing enteritis with pneumoperitoneum involving the ileum. At the time of presentation to the Department of General Surgery, she was asymptomatic and had no abnormal findings on examination other than the imaging findings. DIAGNOSIS: Sunitinib-induced PCI, metastatic RCC, liver cirrhosis, and diabetes mellitus. INTERVENTIONS: She was admitted to the general ward for conservative treatment, and sunitinib was discontinued. Conservative treatments included nil per os, total parenteral nutrition, antibiotics, H2-blockers, and oxygen therapy. OUTCOMES: On the fifth day of hospitalization, the PCI showed moderate resolution on plain radiography, and she was discharged on the seventh day. Follow-up CT imaging 3 months later demonstrated complete resolution of PCI. CONCLUSION: This case emphasizes that the decision between conservative versus surgical treatment for PCI should be based not solely on radiological findings but rather on a comprehensive assessment, including the underlying condition, vital signs, physical examinations, and blood tests.

Thoracic cavity remodeling and pulmonary function change after chest wall resection.

Background: Chest wall resection (CWR) is an essential procedure for treating malignancies and infectious conditions of the chest wall. However, there are few studies on the pulmonary function and changes in thoracic cavity volume (TCV) related to CWR. This study aims to investigate the effects of CWR on long-term changes in TCV and pulmonary function. Methods: Data of patients who underwent CWR between 2001 and 2021 were retrospectively reviewed. Patients who underwent single rib or lung resection rather than wedge resection were excluded. TCV (liter) was defined as the sum of the right and left TCVs (RCV and LCV) and was measured using computed tomography image reconstruction software. Changes in pulmonary function and TCV 1 year postoperatively were analyzed. Results: A total of 45 patients were included. The number of resected ribs was 2 in 16 (35.6%) and ≥3 in 29 (64.4%) patients. Thirty patients underwent reconstruction. Long-term post-CWR decreased in forced vital capacity (FVC) (-7.9%, P=0.004) and forced expiratory volume in 1 second (FEV1) (-7.0%, P=0.002) were significant. There was no significant decrease in FEV1/FVC ratio (-3.0%, P=0.06), diffusing capacity of the lung for carbon monoxide (DLCO) (-5.9%, P=0.18) and TCV (-3.1%, P=0.10). There was no correlation between changes in TCV and decreases in FVC (r=0.12, P=0.56) or FEV1 (r=0.15, P=0.45). After right-side CWR (n=27), RCV (-7.8%, P=0.01) decreased significantly, whereas LCV (+2.1%, P=0.58) did not. The left-side CWR exhibited an identical pattern. (LCV: -8.5%, P=0.004; RCV: +1.3%, P=0.85). In the ≥3 rib-resection group, FVC (-9.5%, P=0.02), FEV1 (-7.9%, P=0.02) and TCV (-6.4%, P=0.04) decreased significantly. No significant changes were noted in the 2 rib-resection group. There were no significant differences in the changes in pulmonary function nor TCV between the reconstruction and no-reconstruction groups. Conclusions: The long-term decrease in pulmonary function after CWR was significant, especially after ≥3-rib resection.

Comparative Study of Indocyanine Green Intravenous Injection and the Inflation-Deflation Method for Assessing Resection Margins in Segmentectomy for Lung Cancer: A Single-Center Retrospective Study.

Background: The inflation-deflation (ID) method has long been the standard for intraoperative margin assessment in segmentectomy. However, with advancements in vision technology, the use of near-infrared mapping with indocyanine green (ICG) has become increasingly common. This study was conducted to compare the perioperative outcomes and resection margins achieved using these methods. Methods: This retrospective study included patients who underwent direct segmentectomy for clinical stage I lung cancer between January 2018 and September 2022. We compared perioperative factors, including bronchial and parenchymal resection margins, according to the margin assessment method and the type of segmentectomy performed. Since the ICG approach was adopted in April 2021, we also examined a recent subgroup of patients treated from then onward. Results: A total of 319 segmentectomies were performed. ID and ICG were utilized for 261 (81.8%) and 58 (18.2%) patients, respectively. Following April 2021, 61 patients (51.3%) were treated with ID, while 58 (48.7%) received ICG. We observed no significant difference in resection margins between ID and ICG for bronchial (2.7 cm vs. 2.3 cm, p=0.07) or parenchymal (2.5 cm vs. 2.3 cm, p=0.46) margins. Additionally, the length of hospitalization and the complication rate were comparable between groups. Analysis of the recent subgroup confirmed these findings, showing no significant differences in resection margins (bronchial: 2.6 cm vs. 2.3 cm, p=0.25; parenchymal: 2.4 cm vs. 2.3 cm, p=0.75), length of hospitalization, or complication rate. Conclusion: The perioperative outcomes and resection margins achieved using ID and ICG were comparable, suggesting that both methods can safely guide segmentectomy procedures.

Enhancing cancer immunotherapy with photodynamic therapy and nanoparticle: making tumor microenvironment hotter to make immunotherapeutic work better.

Cancer immunotherapy has made tremendous advancements in treating various malignancies. The biggest hurdle to successful immunotherapy would be the immunosuppressive tumor microenvironment (TME) and low immunogenicity of cancer cells. To make immunotherapy successful, the 'cold' TME must be converted to 'hot' immunostimulatory status to activate residual host immune responses. To this end, the immunosuppressive equilibrium in TME should be broken, and immunogenic cancer cell death ought to be induced to stimulate tumor-killing immune cells appropriately. Photodynamic therapy (PDT) is an efficient way of inducing immunogenic cell death (ICD) of cancer cells and disrupting immune-restrictive tumor tissues. PDT would trigger a chain reaction that would make the TME 'hot' and have ICD-induced tumor antigens presented to immune cells. In principle, the strategic combination of PDT and immunotherapy would synergize to enhance therapeutic outcomes in many intractable tumors. Novel technologies employing nanocarriers were developed to deliver photosensitizers and immunotherapeutic to TME efficiently. New-generation nanomedicines have been developed for PDT immunotherapy in recent years, which will accelerate clinical applications.

Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles.

Ulcerative colitis is a chronic condition in which a dysregulated immune response contributes to the acute intestinal inflammation of the colon. Current clinical therapies often exhibit limited efficacy and undesirable side effects. Here, programmable nanomicelles were designed for colitis treatment and loaded with RU.521, an inhibitor of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. STING-inhibiting micelles (SIMs) comprise hyaluronic acid-stearic acid conjugates and include a reactive oxygen species (ROS)-responsive thioketal linker. SIMs were designed to selectively accumulate at the site of inflammation and trigger drug release in the presence of ROS. Our in vitro studies in macrophages and in vivo studies in a murine model of colitis demonstrated that SIMs leverage HA-CD44 binding to target sites of inflammation. Oral delivery of SIMs to mice in both preventive and delayed therapeutic models ameliorated colitis's severity by reducing STING expression, suppressing the secretion of proinflammatory cytokines, enabling bodyweight recovery, protecting mice from colon shortening, and restoring colonic epithelium. In vivo end points combined with metabolomics identified key metabolites with a therapeutic role in reducing intestinal and mucosal inflammation. Our findings highlight the significance of programmable delivery platforms that downregulate inflammatory pathways at the intestinal mucosa for managing inflammatory bowel diseases.

Safety of Perioperative Maintenance of Antiplatelet Agents in Elderly Patients Undergoing Lung Cancer Surgery.

Background: The maintenance of antiplatelet therapy increases the risk of bleeding during lung cancer surgery. Conversely, the perioperative interruption of antiplatelet therapy may result in serious thrombotic complications. This study aimed to investigate the safety of continuing antiplatelet therapy in the context of lung cancer surgery. Methods: We retrospectively reviewed a cohort of 498 elderly patients who underwent surgery for lung cancer. These patients were categorized into 2 groups: group N, which did not receive antiplatelet therapy, and group A, which did. Group A was subsequently subdivided into group Am, where antiplatelet therapy was maintained, and group Ai, where antiplatelet therapy was interrupted. We compared the incidence of bleeding-related and thrombotic complications across the 3 groups. Results: There were 387 patients in group N and 101 patients in group A (Ai: 70, Am: 31). No significant differences were found in intraoperative blood loss, thoracotomy conversion rates, transfusion requirements, volume of chest tube drainage, or reoperation rates for bleeding control between groups N and A or between groups Am and Ai. The duration of hospital stay was longer for group A compared to group N (7 days vs. 6 days, p=0.005), but there was no significant difference between groups Ai and Am. The incidence of cardiovascular or cerebrovascular complications did not differ significantly between groups Ai and Am. However, group Ai included a severe case of in-hospital ST-elevation myocardial infarction. Conclusion: The maintenance of antiplatelet therapy was found to be safe in terms of perioperative bleeding and thrombotic complications in elderly lung cancer surgery patients.

Safety of lung resection surgery after severe acute respiratory syndrome coronavirus 2 infection in the post-vaccination era.

OBJECTIVES: To investigate the postoperative outcomes of lung resection in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and determine the optimal timing of surgery. METHODS: This retrospective, single-centre cohort study included patients who underwent lung resection between June 2021 and June 2022. Patients were divided into the coronavirus disease 2019 (COVID-19) and non-COVID-19 groups based on their preoperative SARS-CoV-2 infection history, and postoperative outcomes were compared. Logistic regression analysis was conducted to identify the risk factors of complications after lung resection surgery. RESULTS: In total, 1194 patients were enrolled, of whom, 79 had a history of SARS-CoV-2 infection. In the COVID-19 group, 66 patients (90.4%) had received at least 1 vaccination dose. The average interval between infection and surgery was 67 days, with no significant impact on postoperative outcomes. Regarding postoperative outcomes, there were no significant differences in major complication rate (6.3% vs 5.4%, P = 0.613), respiratory complication rate (19.0% vs 12.2%, P = 0.079) or length of stays (4.9 ± 3.4 vs 5.0 ± 5.6, P = 0.992) between the 2 groups. Multivariate logistic regression analysis revealed that age, male sex, poor pulmonary function test, open surgery and extensive lung resection were risk factors for postoperative complications, while preoperative COVID-19 infection status was not a statistically significant risk factor. CONCLUSIONS: In the post-vaccination era, lung resection surgery can be safely performed shortly after SARS-CoV-2 infection, even within 4 weeks of infection.

"Three-in-one": A Photoactivable Nanoplatform Evokes Anti-Immune Response by Inhibiting BRD4-cMYC-PDL1 Axis to Intensify Photo-Immunotherapy.

Combinatorial immuno-cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable of precise tumor targeting, remote activation, and immune-regulating drug delivery remains a significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ-1) using polypyrrole/hyaluronic acid (PPyHA/JQ-1) are developed. These nanoparticles offer active tumor targeting, photothermal tumor ablation using near-infrared light, and laser-controlled JQ-1 release for efficient breast cancer treatment. When the molecular weight of HA varies (from 6.8 kDa to 3 MDa) in the PPyHA nanoparticles, it is found that the nanoparticles synthesized using 1 MDa HA, referred to as PPyHA (1 m), show the most suitable properties, including small hydrodynamic size, high surface HA contents, and colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ-1 elevates the temperature above 55 °C, which is sufficient for thermal ablation and active release of JQ-1 in the tumor microenvironment (TME). Notably, the controlled release of JQ-1 substantially inhibits the expression of cancer-promoting genes. Furthermore, PPyHA/JQ-1 effectively suppresses the expression of programmed cell death ligand 1 (PD-L1) and prolongs dendritic cell maturation and CD8+ T cell activation against the tumor both in vitro and in vivo. PPyHA/JQ-1 treatment simultaneously provides a significant tumor regression through photothermal therapy and immune checkpoint blockade, leading to a durable antitumor-immune response. Overall, "Three-in-one" immunotherapeutic photo-activable nanoparticles have the potential to be beneficial for a targeted combinatorial treatment approach for TNBC.

Tumor-targeting cell membrane-coated nanorings for magnetic-hyperthermia-induced tumor ablation.

Magnetic hyperthermia has attracted considerable attention for efficient cancer therapy because of its noninvasive nature, deep tissue penetration, and minimal damage to healthy tissues. Herein, we have fused cancer cell membrane fragments with lipids and cloaked them on magnetic nanorings to form targeted Fe nanorings (TF) for tumor-targeted magnetic hyperthermia-induced tumor ablation. In our approach, cell membrane fragments from cancer cells were fused with lipids to form vesicles, which could efficiently encapsulate magnetic nanorings, thereby forming TF. We observed that TF have high tumor uptake via homotypic targeting, where cancer cells take up TF through membrane fusion. Under an external alternating magnetic field (AMF), TF accumulated in the tumors are heated, driving magnetic-hyperthermia-induced tumor cell death. Our in vitro studies show that self-targeting TF efficiently localized in cancer cells and induced cell death with an AMF, which was shown by a live/dead assay. Our findings demonstrate the potential of TF in tumor ablation, thereby making them promising and efficient nanosystems for tumor-targeted theranostics.

The Prognostic Value of Oligo-Recurrence Following Esophagectomy for Esophageal Cancer.

Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). Conclusion: After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.

Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis.

Introduction: To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM). Methods: We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas. Results: A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800). Conclusion: Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC. Trial registration: ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).

Machine-Learning Algorithms Using Systemic Inflammatory Markers to Predict the Oncologic Outcomes of Colorectal Cancer After Surgery.

BACKGROUND: This study aimed to investigate the clinical significance of machine-learning (ML) algorithms based on serum inflammatory markers to predict survival outcomes for patients with colorectal cancer (CRC). METHODS: The study included 941 patients with stages I to III CRC. Based on random forest algorithms using 15 compositions of inflammatory markers, four different prediction scores (DFS score-1, DFS score-2, DFS score-3, and DFS score-4) were developed for the Yonsei cohort (training set, n = 803) and tested in the Ulsan cohort (test set, n = 138). The Cox proportional hazards model was used to determine correlation between prediction scores and disease-free survival (DFS). Harrell's concordance index (C-index) was used to compare the predictive ability of prediction scores for each composition. RESULTS: The multivariable analysis showed the DFS score-4 to be an independent prognostic factor after adjustment for clinicopathologic factors in both the training and test sets (hazard ratio [HR], 8.98; 95% confidence interval [CI] 6.7-12.04; P < 0.001 for the training set and HR, 2.55; 95% CI 1.1-5.89; P = 0.028 for the test set]. With regard to DFS, the highest C-index among single compositions was observed in the lymphocyte-to-C-reactive protein ratio (LCR) (0.659; 95% CI 0.656-0.662), and the C-index of DFS score-4 (0.727; 95% CI 0.724-0.729) was significantly higher than that of LCR in the test set. The C-index of DFS score-3 (0.725; 95% CI 0.723-0.728) was similar to that of DFS score-4, but higher than that of DFS score-2 (0.680; 95% CI 0.676-0.683). CONCLUSIONS: The ML-based approaches showed prognostic utility in predicting DFS. They could enhance clinical use of inflammatory markers in patients with CRC.

CXCR4 Targeting Nanoplatform for Transcriptional Activation of Latent HIV-1 Infected T Cells.

Antiretroviral drugs are limited in their ability to target latent retroviral reservoirs in CD4+ T cells, highlighting the need for a T cell-targeted drug delivery system that activates the transcription of inactivated viral DNA in infected cells. Histone deacetylase inhibitors (HDACi) disrupt chromatin-mediated silencing of the viral genome and are explored in HIV latency reversal. But single drug formulations of HDACi are insufficient to elicit therapeutic efficacy, warranting combination therapy. Furthermore, protein kinase C activators (PKC) have shown latency reversal activity in HIV by activating the NF-κB signaling pathway. Combining HDACi (SAHA) with PKC (PMA) activators enhances HIV reservoir activation by promoting chromatin decondensation and subsequent transcriptional activation. In this study, we developed a mixed nanomicelle (PD-CR4) drug delivery system for simultaneous targeting of HIV-infected CD4+ T cells with two drugs, suberoylanilide hydroxamic acid (SAHA) and phorbol 12-myristate 13-acetate (PMA). SAHA is a HDACi that promotes chromatin decondensation, while PMA is a PKC agonist that enhances transcriptional activation. The physicochemical properties of the formulated PD-CR4 nanoparticles were characterized by NMR, CMC, DLS, and TEM analyses. Further, we investigated in vitro safety profiles, targeting efficacy, and transcriptional activation of inactivated HIV reservoir cells. Our results suggest that we successfully prepared a targeted PD system with dual drug loading. We have compared latency reversal efficacy of a single drug nanoformulation and combination drug nanoformulation. Final PD-SP-CR4 successfully activated infected CD4+ T cell reservoirs and showed enhanced antigen release from HIV reservoir T cells, compared with the single drug treatment group as expected. To summarize, our data shows PD-SP-CR4 has potential T cell targeting efficiency and efficiently activated dormant CD4+ T cells. Our data indicate that a dual drug-loaded particle has better therapeutic efficacy than a single loaded particle as expected. Hence, PD-CR4 can be further explored for HIV therapeutic drug delivery studies.

Clinical characteristics and treatment outcomes of symptomatic Meckel diverticulum: a comparative study among children, adolescent, and adult patients.

Purpose: We investigated the clinical characteristics and treatment outcomes of symptomatic Meckel diverticulum (MD) in adolescents by comparison with children and adults. Methods: We retrospectively reviewed the medical records of patients who underwent symptomatic MD surgery from January 2002 to December 2019. Demographic information, clinical presentations, preoperative evaluations, operative variables, postoperative outcomes, and pathologic findings were collected. We performed analyses by dividing all patients into three groups according to age at surgery: child group (<10 years), adolescent group (10-19 years), and adult group (≥20 years). Results: Forty-three patients underwent symptomatic MD surgery (the child group, 14; the adolescent group, 17; and the adult group, 12). Vomiting and intestinal obstruction decreased significantly with age (P = 0.042 and 0.001), whereas hematochezia and gastrointestinal bleeding showed an increasing trend with age, although not statistically significant (P = 0.064 and 0.064). Ultrasound performance decreased significantly with age (P = 0.002), whereas CT performance showed an increasing trend with age, although not statistically significant (P = 0.193). Preoperative diagnosis rate increased significantly with age (P = 0.029). Laparoscopic surgery was performed significantly more in the adult group than in other groups (P = 0.001). The sizes of MD were significantly greater in the adolescent group than in other groups (P = 0.006 and 0.002). Conclusion: The clinical characteristics and treatment outcomes of symptomatic MD in adolescents exhibit a transitional pattern between children and adults. Therefore, it is important for clinicians to recognize that adolescent patients with symptomatic MD have the characteristics of both children and adult patients to ensure optimal care.