Minimally invasive total pancreatectomy with islet autotransplantation for chronic pancreatitis: the robotic approach.

INTRODUCTION: Total pancreatectomy with islet autotransplantation (TPIAT) treats refractory pain in chronic pancreatitis, prevents episodes of acute exacerbation, and mitigates postoperative brittle diabetes. The minimally invasive (MIS) approach offers a decreased surgical access trauma and enhanced recovery. Having established a laparoscopic TPIAT program, we adopted a robotic approach (R-TPIAT) and studied patient outcomes compared to open TPIAT. METHODS: Between 2013 and 2021, 61 adult patients underwent TPIAT after a comprehensive evaluation (97% chronic pancreatitis). Pancreatic islets were isolated on-site during the procedure. We analyzed and compared intraoperative surgical and islet characteristics, postoperative morbidity and mortality, and 1-year glycemic outcomes. RESULTS: MIS-TPIAT was performed in 41 patients (67%, 15 robotic and 26 laparoscopic), and was associated with a shorter mean length of intensive care unit stay compared to open TPIAT (2.9 vs 4.5 days, p = 0.002). R-TPIAT replaced laparoscopic TPIAT in 2017 as the MIS approach of choice and demonstrated decreased blood loss compared to open TPIAT (324 vs 843 mL, p = 0.004), similar operative time (609 vs 562 min), 30-day readmission rate (7% vs 15%), and 90-day complication rate (13% vs 20%). The glycemic outcomes including C-peptide detection at 1-year (73% vs 88%) and insulin dependence at 1-year (75% vs 92%) did not differ. The mean length of hospital stay after R-TPIAT was 8.6 days, shorter than for laparoscopic (11.5 days, p = 0.031) and open TPIAT (12.6 days, p = 0.017). Both MIS approaches had a 1-year mortality rate of 0%. CONCLUSIONS: R-TPIAT was associated with a 33% reduction in length of hospital stay (4-day benefit) compared to open TPIAT. R-TPIAT was similar to open TPIAT on measures of feasibility, safety, pain control, and 1-year glycemic outcomes. Our data suggest that robotic technology, a new component in the multidisciplinary therapy of TPIAT, is poised to develop into the primary surgical approach for experienced pancreatic surgeons.

Germline Pathogenic Variants in Patients With Pancreatic and Periampullary Cancers.

PURPOSE: Inherited cancer susceptibility is often not suspected in the absence of a significant cancer family history. Pathogenic germline variants in pancreatic cancer are well-studied, and routine genetic testing is recommended in the guidelines. However, data on rare periampullary cancers other than pancreatic cancer are insufficient. We compared the prevalence of germline susceptibility variants in patients with pancreatic cancer and nonpancreatic periampullary cancers. MATERIALS AND METHODS: Six hundred and eight patients who had undergone pancreaticoduodenal resection at a tertiary referral hospital were studied, including 213 with pancreatic ductal adenocarcinoma, 172 with ampullary cancer, 154 with distal common bile duct cancer, and 69 with duodenal adenocarcinoma. Twenty cancer susceptibility and candidate susceptibility genes were sequenced, and variant interpretation was assessed by interrogating ClinVar and PubMed. RESULTS: Pathogenic or likely pathogenic, moderate- to high-penetrant germline variants were identified in 46 patients (7.7%), including a similar percentage of patients with pancreatic (8.5%) and nonpancreatic periampullary cancer (7.1%). Low-penetrant variants were identified in an additional 11 patients (1.8%). Eighty-nine percent of the moderate- to high-penetrant variants involved the major cancer susceptibility genes BRCA2, ATM, BRCA1, CDKN2A, MSH2/MLH1, and PALB2; the remaining 11% involved other cancer susceptibility genes such as BRIP1, BAP1, and MSH6. Almost all pathogenic variant carriers had a family history of cancer. CONCLUSION: Patients with pancreatic and nonpancreatic periampullary cancer have a similar prevalence of pathogenic cancer susceptibility variants. Germline susceptibility testing should be considered for patients with any periampullary cancer.

Discovery of Novel p53-MDM2 Inhibitor (RG7388)-Conjugated PlatinumIV Complexes as Potent Antitumor Agents.

While a number of p53-MDM2 inhibitors have progressed into clinical trials for the treatment of cancer, their progression has been hampered by a variety of problems, including acquired drug resistance, dose-dependent toxicity, and limited clinical efficiency. To make more progress, we integrated the advantages of MDM2 inhibitors and platinum drugs to construct novel PtIV-RG7388 (a selective MDM2 inhibitor) complexes. Most complexes, especially 5a and 5b, displayed greatly improved antiproliferative activity against both wild-type and mutated p53 cancer cells. Remarkably, 5a exhibited potent in vivo tumor growth inhibition in the A549 xenograft model (66.5%) without apparent toxicity. It arrested the cell cycle at both the S phase and the G2/M phase and efficiently induced apoptosis via the synergistic effects of RG7388 and cisplatin. Altogether, PtIV-RG7388 complex 5a exhibited excellent in vitro and in vivo antitumor activities, highlighting the therapeutic potential of PtIV-RG7388 complexes as antitumor agents.

Predictors for Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Improved systemic therapy has made long term (≥ 5 years) overall survival (LTS) after resection of pancreatic ductal adenocarcinoma (PDAC) increasingly common. However, a systematic review on predictors of LTS following resection of PDAC is lacking. METHODS: The PubMed, Embase, Scopus, and Cochrane CENTRAL databases were systematically searched from inception until March 2023. Studies reporting actual survival data (based on follow-up and not survival analysis estimates) on factors associated with LTS were included. Meta-analyses were conducted by using a random effects model, and study quality was gauged by using the Newcastle-Ottawa Scale (NOS). RESULTS: Twenty-five studies with 27,091 patients (LTS: 2,132, non-LTS: 24,959) who underwent surgical resection for PDAC were meta-analyzed. The median proportion of LTS patients was 18.32% (IQR 12.97-21.18%) based on 20 studies. Predictors for LTS included sex, body mass index (BMI), preoperative levels of CA19-9, CEA, and albumin, neutrophil-lymphocyte ratio, tumor grade, AJCC stage, lymphovascular and perineural invasion, pathologic T-stage, nodal disease, metastatic disease, margin status, adjuvant therapy, vascular resection, operative time, operative blood loss, and perioperative blood transfusion. Most articles received a "good" NOS assessment, indicating an acceptable risk of bias. CONCLUSIONS: Our meta-analysis pools all true follow up data in the literature to quantify associations between prognostic factors and LTS after resection of PDAC. While there appears to be evidence of a complex interplay between risk, tumor biology, patient characteristics, and management related factors, no single parameter can predict LTS after the resection of PDAC.

Outpatient and Ambulatory Extended Recovery Robotic Hepatectomy: Multinational Study of 307 Cases.

BACKGROUND: For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this "incision dominant procedure" into a safe outpatient procedure. STUDY DESIGN: We audited outpatient (<2 midnights) robotic hepatectomies at six hepatobiliary centers in two nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure. ERAS programs were active at all sites, and home digital monitoring was available at one of the institutions. RESULTS: Three hundred and seven outpatient (26 same-day, 281 next-day discharge) robotic hepatectomies were identified (2013-2023). Most were minor hepatectomies (194 single-segments, 90 bi-segmentectomies, 14 three-segments, 8 four-segments). Thirty-nine (13%) were for benign histology, while 268 were for cancer (33 hepatocellular carcinoma, 27 biliary, 208 metastatic disease). Patient characteristics were - median age 60 (18-93), 55% male, and median BMI 26 (14-63). Thirty (10%) had cirrhosis. One-hundred-eighty-seven (61%) had previous abdominal surgery. Median operative time was 163 minutes (30-433), with a median blood loss of 50 cc (10-900). There were no deaths and six complications (2%): 2 wound infections, 1 failure to thrive, and 3 perihepatic abscesses. Re-admission was required in 5 patients (1.6%).Of the 268 malignancy cases, 25 (9%) were R1 resections. Of the 128 with superior segment resections (segments 7/8/4A/2/1), there were 12 positive margins (9%) and two readmissions for abscess. CONCLUSIONS: Outpatient robotic hepatectomies in well-selected cases are safe (0 mortality, 2% complication, 1.6% re-admission), including resections in the superior or posterior portions of the liver that are challenging with non-articulating laparoscopic instruments.

Defining the Minimal and Optimal Thresholds for Lymph Node Resection and Examination for Intraductal Papillary Mucinous Neoplasm Derived Pancreatic Cancer: A Multicenter Retrospective Analysis.

OBJECTIVE: To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value. BACKGROUND: Current guidelines recommend a minimum of 12-15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC. METHODS: Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cut-off for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cut-off (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox-regression was used to determine hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS: In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 (P=0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs. 37.2 mo, P<0.001). Optimal lymphadenectomy was associated with improved OS [HR:0.57 (95%CI 0.39-0.83)] and RFS [HR:0.70 (95%CI 0.51-0.97)] on multivariable Cox-regression. On sub-analysis the optimal lymphadenectomy cut-offs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 (P<0.001), 23 (P=0.160), and 25 (P=0.008). CONCLUSION: In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates under-staging, and at least 20 lymph nodes is associated with the improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cut-offs.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVE: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). METHODS: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. RESULTS: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). CONCLUSION: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

An Innovative Preauricular Free Flap Pedicled with Retrograde Vascular (PFFPRV) for Pediatric Nasal Reconstruction.

SUMMARY: Nasal reconstruction in pediatric patient is very challenging and it requires consideration of later nasal development. Herein, we introduce an innovative preauricular free flap pedicled with retrograde vascular (PFFPRV) for pediatric nasal reconstruction. In this PFFPRV technique, the retrograde superficial temporal vessels were used as the flap pedicle. The lateral alar artery and angular vein were used as vessels of the nasal recipient zone. The flap vessels were anastomosed directly to the recipient area vessels without additional vessel transplantation. Eight pediatric patients with nasal defects underwent this operation. All patients were followed up for more than 2 years. Patients' medical history data were retrospectively analyzed. Preoperative and postoperative facial photos were compared and analyzed. The satisfaction of patient's parents with the aesthetic results was assessed. All patients were successfully operated without intraoperative complications. None of the procedures required additional blood vessel grafts. One patient developed a vascular crisis the next day after the surgery and underwent vascular exploration operation. The free flaps of all patients survived without wound infection or necrosis. The color difference of flap gradually became unobvious. The transplanted flap did not show obvious contracture or retraction, and the nose was symmetrical and developed well. The parents of all patients were satisfied with the surgical results. We think this PFFPRV technique can be a reasonable alternative strategy for reconstruction of pediatric nasal defect, with no adverse effect on nasal development and no need of vascular transplantation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Magnetic-driven hydrogel microrobots for promoting osteosarcoma chemo-therapy with synthetic lethality strategy.

The advancements in the field of micro-robots for drug delivery systems have garnered considerable attention. In contrast to traditional drug delivery systems, which are dependent on blood circulation to reach their target, these engineered micro/nano robots possess the unique ability to navigate autonomously, thereby enabling the delivery of drugs to otherwise inaccessible regions. Precise drug delivery systems can improve the effectiveness and safety of synthetic lethality strategies, which are used for targeted therapy of solid tumors. MYC-overexpressing tumors show sensitivity to CDK1 inhibition. This study delves into the potential of Ro-3306 loaded magnetic-driven hydrogel micro-robots in the treatment of MYC-dependent osteosarcoma. Ro-3306, a specific inhibitor of CDK1, has been demonstrated to suppress tumor growth across various types of cancer. We have designed and fabricated this micro-robot, capable of delivering Ro-3306 precisely to tumor cells under the influence of a magnetic field, and evaluated its chemosensitizing effects, thereby augmenting the therapeutic efficacy and introducing a novel possibility for osteosarcoma treatment. The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel micro-robots present a novel strategy for enhancing the chemosensitivity of MYC-dependent osteosarcoma, paving the way for new possibilities in future clinical applications.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell-cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation. SIGNIFICANCE: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.

Comparison of Thoracoscopy-Guided Thoracic Paravertebral Block and Ultrasound-Guided Thoracic Paravertebral Block in Postoperative Analgesia of Thoracoscopic Lung Cancer Radical Surgery: A Randomized Controlled Trial.

INTRODUCTION: Ultrasound-guided thoracic paravertebral block (UTPB) is widely used for postoperative analgesia in thoracic surgery. However, it has many disadvantages. Thoracoscopy-guided thoracic paravertebral block (TTPB) is a new technique for thoracic paravertebral block (TPB). In this study, we compared the use of TTPB and UTPB for pain management after thoracoscopic radical surgery for lung cancer. METHODS: In total, 80 patients were randomly divided 1:1 into the UTPB group and the TTPB group. The surgical time of TPB, the success rate of the first puncture, block segment range, visual analog scale (VAS) scores at 2, 6, 12, 24, and 48 h post operation, and the incidence of postoperative adverse reactions were compared between the two groups. RESULTS: The surgical time of TPB was significantly shorter in the TTPB group than in the UTPB group (2.2 ± 0.3 vs. 5.7 ± 1.7 min, t = - 12.411, P < 0.001). The success rate of the first puncture and the sensory block segment were significantly higher in the TTPB group than in the UTPB group (100% vs. 76.9%, χ2 = 8.309, P < 0.001; 6.5 ± 1.2 vs. 5.1 ± 1.3 levels, t = - 5.306, P < 0.001, respectively). The VAS scores were significantly higher during rest and coughing at 48 h post operation than at 2, 6, 12, and 24 h post operation in the TTPB group. The VAS scores were significantly lower during rest and coughing at 12 and 24 h post operation in the TTPB group than in the UTPB group (rest: 2.5 ± 0.4 vs. 3.4 ± 0.6, t = 7.325, P < 0.001; 2.5 ± 0.5 vs. 3.5 ± 0.6, t = 7.885, P < 0.001; coughing: 3.4 ± 0.6 vs. 4.2 ± 0.7, t = 5.057, P < 0.001; 3.4 ± 0.6 vs. 4.2 ± 0.8, t = 4.625, P < 0.001, respectively). No significant difference was observed in terms of postoperative adverse reactions between the two groups. CONCLUSIONS: Compared with UTPB, TTPB shows advantages, such as simpler and more convenient surgery, shorter surgical time, a higher success rate of the first puncture, wider block segments, and superior analgesic effect. TTPB can effectively reduce postoperative pain due to thoracoscopic lung cancer radical surgery. TRIAL REGISTRATION: https://www.chictr.org.cn , identifier ChiCTR2300072005, prospectively registered on 31/05/2023.

Germline Testing identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors.

10% of pancreatic neuroendocrine tumors (pNETs) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathological/likely pathological germline variants (P/LP) in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center (MDACC) and Johns Hopkins Hospital (JHH). High-risk cohort included (n=132) patients seen at MDACC who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer and syndromic features) between 2013-2019. Unselected cohort (n=106) patients seen at JHH who underwent germline testing following their diagnosis of pNETs between 2020 to 2022. In the high-risk cohort (n=132), 33% (n=44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n=25), followed by DNA repair pathways 18% (n=8), and 7 %(n=3) in MSH2 (Lynch Syndrome). Patients with P/LP were younger (45 years vs 50 years; p=0.002). In the unselected cohort (n=106), 21% (n=22) had P/LP. The majority were noted in DNA repair pathways 40% (n=9) and MEN1 36% (n=8). Multifocal tumors correlated with the presence of P/LP (p=0.0035). MEN1 germline P/LP variants correlated with younger age (40 vs 56 years) (p=0.0012). presence of multifocal tumors (p<0.0001), and WHO grade 1 histology (p=0.0078). P/LP variants are prevalent in patients with clinically sporadic pNET irrespective of high-risk features. The findings support upfront universal germline testing in all pNET patients.

Targeted Drug Delivery to ACE2+ Cells Using Engineered Extracellular Vesicles: A Potential Therapeutic Approach for COVID-19.

BACKGROUND: Extracellular vesicles (EVs) are emerging as potential drug carriers in the fight against COVID-19. This study investigates the ability of EVs as drug carriers to target SARS-CoV-2-infected cells. METHODS: EVs were modified using Xstamp technology to carry the virus's RBD, enhancing targeting ability to hACE2+ cells and improving drug delivery efficiency. Characterization confirmed EVs' suitability as drug carriers. For in vitro tests, A549, Caco-2, and 4T1 cells were used to assess the targeting specificity of EVRs (EVs with membrane-surface enriched RBD). Moreover, we utilized an ex vivo lung tissue model overexpressing hACE2 as an ex vivo model to confirm the targeting capability of EVRs toward lung tissue. The study also evaluated drug loading efficiency and assessed the potential of the anti-inflammatory activity on A549 lung cancer cells exposed to lipopolysaccharide. Results demonstrate the successful construction of RBD-fused EVRs on the membrane-surface. In both in vitro and ex vivo models, EVRs significantly enhance their targeting ability towards hACE2+ cells, rendering them a safe and efficient drug carrier. Furthermore, ultrasound loading efficiently incorporates IL-10 into EVRs, establishing an effective drug delivery system that ameliorates the pro-inflammatory response induced by LPS-stimulated A549 cells. CONCLUSION: These findings indicate promising opportunities for engineered EVs as a novel nanomedicine carrier, offering valuable insights for therapeutic strategies against COVID-19 and other diseases.

Factors associated with radiological misstaging of pancreatic ductal adenocarcinoma: A retrospective observational study.

PURPOSE: Accurate staging of disease is vital in determining appropriate care for patients with pancreatic ductal adenocarcinoma (PDAC). It has been shown that the quality of scans and the experience of a radiologist can impact computed tomography (CT) based assessment of disease. The aim of the current study was to evaluate the impact of the rereading of outside hospital (OH) CT by an expert radiologist and a repeat pancreatic protocol CT (PPCT) on staging of disease. METHODS: Patients evaluated at the our institute's pancreatic multidisciplinary clinic (2006 to 2014) with OH scan and repeat PPCT performed within 30 days were included. In-house radiologists staged disease using OH scans and repeat PPCT, and factors associated with misstaging were determined. RESULTS: The study included 100 patients, with a median time between OH scan and PPCT of 19 days (IQR: 13-23 days.) Stage migration was mostly accounted for by upstaging of disease (58.8 % to 83.3 %) in all comparison groups. When OH scans were rereviewed, 21.5 % of the misstaging was due to missed metastases, however, when rereads were compared to the PPCT, occult metastases accounted for the majority of misstaged patients (62.5 %). Potential factors associated with misstaging were primarily related to imaging technique. CONCLUSION: A repeat PPCT results in increased detection of metastatic disease that rereviews of OH scans may otherwise miss. Accessible insurance coverage for repeat PPCT imaging even within 30 days of an OH scan could help optimize delivery of care and alleviate burdens associated with misstaging.

Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

The residual rate of HPV and the recurrence rate of CIN after LEEP with negative margins: A meta-analysis.

BACKGROUND: HPV is detected in up to 47% of CIN and up to 70% of cervical cancers. It can cause intraepithelial neoplasia, which can eventually progress to invasive carcinoma. Almost all cervical cancers are caused by HPV. Therefore, it is especially important to treat high-risk HPV. For patients who have undergone LEEP surgery, this procedure can effectively treat CIN. However, it has not been studied in a meta-analysis whether HPV remains after the surgery and whether residual HPV increases the recurrence risk of CIN. To address this gap, our study collected all relevant literature to investigate the residual rate of HPV and its potential influence on the recurrence rate of CIN. We aim to provide valuable recommendations for clinicians and patients. METHODS: The Cochrane Library, EMBASE, and PubMed databases were searched from the establishment of the database until October 2023. Stata 12.0 software was used for the statistical analysis. RESULTS: Twelve studies were included, with a total sample size of 1192 cases. The meta-analysis found that the recurrence rate of CIN was quite low [95% CI = 0.5% (0.001, 0.012); P = 0.006] when the margins were negative after LEEP and there was no residual HPV. When HPV was present, the recurrence rate of CIN was significantly higher [95% CI = 18% (0.089, 0.291), P = 0.000], even if the margins were negative. The recurrence rate of CIN with residual HPV was 3.6 times higher than the recurrence rate of CIN without residual HPV. The residual rate of HPV after LEEP with negative margins was 22.7% [95% CI (0.167, 0.294), P = 0.000], which remained relatively high. CONCLUSION: This meta-analysis found that the recurrence rate of CIN without residual HPV and with negative margins after LEEP was quite low, at 0.5%. However, when HPV was residual, the recurrence rate of CIN significantly increased to 18%, even if the margins were negative. The residual rate of HPV was 22.7%, even when the margins were negative after LEEP.

Using Tumor Marker Gene Variants to Improve the Diagnostic Accuracy of DUPAN-2 and Carbohydrate Antigen 19-9 for Pancreatic Cancer.

PURPOSE: Circulating carbohydrate antigen 19-9 (CA19-9) levels reflect FUT3 and FUT2 fucosyltransferase activity. Measuring the related glycan, DUPAN-2, can be useful in individuals unable to synthesize CA19-9. We hypothesized that similar to CA19-9, FUT functional groups determined by variants in FUT3 and FUT2 influence DUPAN-2 levels, and having tumor marker reference ranges for each functional group would improve diagnostic performance. MATERIALS AND METHODS: Using a training/validation study design, FUT2/FUT3 genotypes were determined in 938 individuals from Johns Hopkins Hospital: 607 Cancer of the Pancreas Screening (CAPS) study subjects with unremarkable pancreata and 331 with pancreatic ductal adenocarcinoma (PDAC). Serum DUPAN-2 and CA19-9 levels were measured by immunoassay. RESULTS: In controls, three functional FUT groups were identified with significant differences in DUPAN-2 levels: FUT3-intact, FUT3-null/FUT2-intact, and FUT3-null/FUT2-null. DUPAN-2 training set diagnostic cutoffs for each FUT group yielded higher diagnostic sensitivity in the validation set for patients with stage I/II PDAC than uniform cutoffs (60.4% [95% CI, 50.2 to 70.0] v 39.8% [30.0 to 49.8]), at approximately 99% (96.7 to 99.6) specificity. Combining FUT/CA19-9 and FUT/DUPAN-2 tests yielded 78.4% (72.3 to 83.7) sensitivity for stage I/II PDAC, at 97.7% (95.3 to 99.1) specificity in the combined sets, with higher AUC (stage I/II: 0.960 v 0.935 for CA19-9 + DUPAN-2 without the FUT test; P < .001); for stage I PDAC, sensitivity was 62.0% (49.1 to 73.2; AUC, 0.919 v 0.883; P = .03). CA19-9 levels in FUT3-null/FUT2-null PDAC subjects were higher than in FUT3-null/FUT2-intact subjects (median/IQR; 24.9/57.4 v <1/2.3 U/mL; P = .0044). In a simulated CAPS cohort, AUC precision recall (AUCPR) scores were 0.51 for CA19-9 alone, 0.64 for FUT/CA19-9, 0.73 for CA19-9/DUPAN-2, and 0.84 for FUT/CA19-9/DUPAN-2. CONCLUSION: Using a tumor marker gene test to individualize CA19-9 and DUPAN-2 reference ranges achieves high diagnostic performance for stage I/II pancreatic cancer.