Objectives To characterize the clinical phenotypes and genotypic spectrum of cystic fibrosis (CF) in Chinese children. Study design We recruited and characterized the phenotypes of 21 Chinese ...children with CF. All 27 exons and their flanking sequences of the CF transmembrane conductance regulator gene were amplified and sequenced to define the genotypes. Results Bronchiectasis (95.2%) and sinusitis (76.2%) were the most common clinical presentations among our patients. By contrast, pancreatic insufficiency was rare (14.3%). The predominant organism found in the airways was Pseudomonas aeruginosa (66.7%). There were obvious reductions of forced expiratory volume in the first second (mean ± SD: 71.8% ± 17.2% predicted) and forced expiratory flows at 75% of exhaled vital capacity (33.7% ± 20.4% predicted) in children with CF. Overall, we identified 22 different mutations, including 12 missense, 5 nonsense, 2 frameshift, 1 in-frame insertion, 1 splice site, and 1 3′untranslated region mutation. Of these, 7 were novel observations (W216X780G→A, 1092insA, Q359X, D567Y, 2623-126T→C, 3439delA and 4575+110C→G), and the most common types were L88X and I556V. One de novo mutation (1092insA) was also revealed. Except for N1303K and R334W, none of them were present in the common Caucasian CF transmembrane conductance regulator mutation-screening panels. Conclusions There was a 5.7-year delay between the first clinical presentation and the eventual CF diagnosis, suggesting that CF may be underdiagnosed in China. The clinical phenotypes and genotypic spectrum are different from that observed in Caucasians.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and ...prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status. We analyzed a spectrum of benign (n = 24), borderline (n = 27), and malignant (n = 19) spitzoid lesions for p16 protein expression by immunohistochemistry and CDKN2A copy number by FISH. Immunohistochemistry was evaluated by two scoring methods: h-score and two-tiered score (positive or negative for p16 loss). By immunohistochemistry, loss of p16 expression was not observed in Spitz nevi (0/24), but was seen in ASTs (7/27, 26%) and spitzoid melanomas (3/19, 16%). By h-score, p16 expression was significantly higher in Spitz nevi relative to ASTs or spitzoid melanomas. Similarly, copy number aberrations of CDKN2A by FISH were absent in Spitz nevi, but were found in 2/21 (9.5%) ASTs and 4/12 (33%) spitzoid melanomas. Our findings from this large cohort suggest p16 aberrations are highly specific for borderline and malignant spitzoid neoplasms relative to Spitz nevi. Similar to ASTs, p16 loss in spitzoid melanomas may occur in the presence or absence of genomic CDKN2A loss.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Objective To identify circulating tumor cells (CTCs) in the blood of patients with early-stage lung cancer and to show that sampling pulmonary vein (PV) blood using microfluidic chip ...technology will yield significantly more CTCs. Improving early detection of lung cancer is critical to improving lung cancer survival. Reproducible detection of CTCs is limited currently in early stage tumors. Methods Patients undergoing pulmonary resection had PV blood drawn before resection. Peripheral blood was sampled at preoperative, intraoperative, and postoperative times. Samples were analyzed on microfluidic chips using antibody-based capture. Results A total of 32 patients with primary lung cancer were evaluated. Twenty patients had 1 or more CTCs detected in at least 1 sample (62.5%). The mean number of CTCs from peripheral vein sources at the preoperative, intraoperative, and postoperative time points was 1.3, 1.9, and 0.6 respectively. The average number of CTCs in the PV was 340.0 (range, 0.0-5422.50; P > .01). When PV CTCs were present, the number of CTCs was correlated with pathological tumor size ( P = .0236). The number of PV CTCs was not correlated with any other clinical feature (eg, smoking status, preoperative or postoperative stage). Furthermore, the number of PV CTCs was significantly higher when preoperative bronchoscopic biopsy was performed, compared with computed tomography–guided biopsy ( P = .0311). Seven patients had evidence of CTC clusters, or microemboli. Conclusions With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and Aims Mucosal lift is critical for successful endoscopic treatment. Normal saline (NS) solution is widely used as the submucosal filler, but its short persistency restricts clinical ...endoscopic submucosal dissection (ESD). In this study, thermo-sensitive isopentane was introduced for submucosal injection. With a boiling point at 27.8°C, liquid isopentane can be easily applied, and gasification inflation can provide great support for submucosal lifting at body temperature. The feasibility and efficiency of isopentane were evaluated in this study. Methods Porcine stomachs were used for in vitro evaluation. A 37°C water bath was used to mimic body temperature. Compared with NS, isopentane was studied for its lifting performance, including injection dosage, persistence of lifting strength, and efficacy for assisting submucosal dissection. The changes in submucosal tissue were also compared. For in vivo evaluation, rats were used to further compare the differences between isopentane and NS, including lifting efficacy, pathologic effect, and safety. Results Compared with NS, the maximum lifting height was achieved with less isopentane (2% NS volume). Longer persistency and faster operation for submucosal dissection were also recorded for isopentane during the in vitro study. Aerification resulted in vacuolization of submucosal connective tissue, which facilitates EMR and postoperative recovery. The same results were confirmed in the rat model. With the same dosage, isopentane produced better mucosal elevation and larger range than NS. According to the histologic examination, no tissue injury was observed with isopentane application. Conclusions As a submucosal injection agent, the feasibility, efficacy, and safety of isopentane has been demonstrated. Thermo-sensitive aerification may be a promising approach to facilitate ESD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objectives
This study aims to investigate whether PD-1 expressions are abnormal in patients with TAK.
Methods
PD-1 expression was analyzed by flow cytometry. Serum cytokines IL-10, IL-7, IL-2, IL-15, ...CCL2, CCL3, and CXCL10 were detected using a cytokine cytometric bead array. Immunohistochemistry staining analysis was used to test PD-1 and programmed death-ligand 1 (PD-L1) expression in the aorta of three patients with TAK and three patients with atherosclerosis as controls.
Results
The mean fluorescence intensity of PD-1 in CD4+PD-1+ cells was decreased in patients with TAK and the frequency of CD4+Foxp3−PD-1+ cells among CD4+T cells was also decreased in peripheral blood relative to healthy controls (P < .05). The percentage of CD4+CD25+Foxp3+PD-1+ cells in the CD4+CD25+T cell population was lower in patients with TAK than in healthy control and was lower in active TAK group (P < .05). Comparing PD-1 and PDL-1 expression in aorta tissue showed that patients with TAK tended to have lower levels than patients with atherosclerosis, but the difference was not significant (P > .05). Patients with TAK had higher serum levels of IL-10, IL-7, CCL2, and CCL3 (P < .05).
Conclusions
Abnormal expression of PD-1 in serum and aorta tissue of patients with TAK may contribute to TAK pathogenesis.
Key points
PD-1 expression in both peripheral blood and aorta tissue of TAK patients decreased relative to healthy controls, indicating that PD-1 might be involved in TAK pathogenesis.
Epidermal growth factor receptor (EGFR) mutations are common driver genes in nonsmall-cell lung cancer and have different sensitivities to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). EGFR is divided ...into classic mutations and rare mutations. Classic mutations are well known, but the understanding of rare mutations is not sufficient. In this article, we summarize the clinical research and treatment progress of rare mutations for different EGFR-TKIs and provide a basis for clinical treatment decisions.
Abstract Objective While robotic-assisted thoracic surgery (RATS) provides improved dexterity, the effect of RATS on pain compared to VATS or open lobectomy is poorly understood. This study evaluated ...acute and chronic pain following RATS, VATS, and open anatomic pulmonary resection. Methods A retrospective review of 498 patients (502 procedures) who underwent RATS (74), VATS (227), and open (201) anatomic pulmonary resection including lobectomy and segmentectomy from 2010 to 2014 was performed to identify factors related to acute and chronic pain. Acute pain scores were analyzed over the first 9 postoperative days. Chronic pain was assessed using the validated PainDETECT survey. Results There were no significant differences in acute or chronic pain between RATS and VATS. There was a significant decrease in acute pain for minimally invasive (MIS) patients (p=0.0004). Chronic numbness was significantly higher after open resection (25.5% vs. 11.6%; p=0.0269) but with no difference in other symptoms of chronic pain. Despite no significant difference in pain scores, 69.2% of RATS patients felt the approach affected pain vs. 44.2% VATS (p=0.0330). On multivariable analysis, younger age (p<0.0001), female gender (p=0.0364), and baseline narcotic use (p=0.0142) were associated with acute pain while younger age (0.0021) and major complications (p=0.0003) were associated with chronic numbness in MIS patients. Conclusions While minimally invasive approaches resulted in less acute pain and chronic numbness, there were no significant differences between RATS and VATS. In contrast, more RATS patients believed the approach affected their pain, suggesting a difference between reality and perception.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial ...chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.
Objective Interest in cardiothoracic surgery (CTS) as a career has decreased over the past decade. Anecdotal evidence suggests that many surgeons develop an interest in CTS before medical school and ...even before college. This study evaluates the interest of high-school students at a magnet high school, with regard to careers in medicine, in surgery, and in CTS. Design A survey assessing career interests and values was conducted among junior and senior high-school students. Students were given a 1-hour presentation by a cardiothoracic (CT) surgeon on the postgraduate training process and then completed a postpresentation survey. Setting A magnet math and science high school, the Kalamazoo Area Mathematics and Science Center. Participants Of 128 students, 117 (91% response rate) completed the survey. Results Overall, 38% of students reported having a high interest in medicine; of this group, 58% reported a high interest in surgery and 36% reported having a high interest in CTS. Men were more likely than women were to have a high interest in surgery and CTS (p < 0.001). Students with at least 1 family member as a physician vs those without were more likely to be interested in medicine, surgery, and CTS and also have a higher level of concern for postgraduation debt (p < 0.01). Women were more likely than men were to have a high level of concern about postgraduation debt (p = 0.018). After a presentation by a CT surgeon, students showed no changes in interest in medicine careers but did report an increased level of knowledge about the process of becoming a CT surgeon, going from 31% to 72%. Conclusions There exists a large interest in both surgery and CTS at the high-school level, but there may be a need for more active outreach to maintain and foster their interest in surgery and CTS through undergraduate and medical school.
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