Background Given the high morbidity and mortality rates for surgery and the diminishment of quality of life caused by operative resection of the gastric cardia, a minor invasive treatment without ...loss of curability is desirable for submucosal tumors (SMTs) of the esophagogastric junction (EGJ). Endoscopic submucosal dissection (ESD) has been used successfully for the removal of esophageal or gastric SMTs; however, the EGJ has been regarded as a difficult location for ESD because of its narrow lumen and sharp angle. Objective To evaluate the clinical impact of ESD for SMTs of the EGJ arising from the muscularis propria layer. Design Single-center, prospective study. Setting Academic medical center. Patients 143 patients with 143 SMTs of the EGJ originating from the muscularis propria layer. Interventions ESD. Main Outcome Measurements Complications, en bloc resection rate, local recurrence, and distant metastases. Results The average maximum diameter of the lesions was 17.6 mm (range 5 - 50 mm). The en bloc resection rate was 94.4% (135/143). All en bloc resection lesions showed both lateral and deep tumor-free margins, including 20 GI stromal tumors. Perforations occurred in 6 patients (4.2%, 6/143), and metal clips were used to occlude the defect. Four pneumoperitoneum and 2 pneumothorax caused by perforations were resolved with nonsurgical treatment. Local recurrence and distant metastasis have not occurred during a 2-year follow-up. Limitations Single-center, short follow-up. Conclusions ESD appears to be a safe, feasible, and effective procedure for providing accurate histopathologic evaluations, as well as curative treatments for SMTs of the EGJ originating from the muscularis propria layer.
Objective The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic ...lymphohistiocytosis (HLH) in febrile children. Study design In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques. Results Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%. Conclusions The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.
Summary We report 3 new patients with sinonasal renal cell–like adenocarcinoma (SNRCLA). One case submitted in consultation demonstrated robust carbonic anhydrase IX (CA-IX) expression, leading us to ...a broader inquiry of CA-IX and carbonic anhydrase II (CA-II) expression in other SNRCLA, Schneiderian tissues, and histologic mimickers. Robust cytoplasmic and membranous CA-IX expression is demonstrated in 6 of 7 SNRCLAs; CA-II expression was demonstrated in 2 of 5 cases. Robust, diffuse CA-II expression is demonstrated throughout sinonasal seromucinous glands in all 10 normal Schneiderian samples. CA-IX is also expressed in all normal sinonasal samples, albeit focally. The closest salivary mimic to SNRCLA is hyalinizing salivary clear cell carcinoma; only focal CA-IX expression was demonstrated in 1 of 2 cases studied. Carbonic anhydrase expression in Schneiderian tissue speaks to its role in regulating the ion concentration of sinonasal secretions and may also explain the origin of this rare tumor.
Objective: To evaluate the reliability of ultrasonographic (US) elastography of the sternocleidomastoid (SCM) muscle and to define normal strain ratio and shear wave velocity (SWV) values in healthy ...infants. Methods: Two hundred healthy infants (mean age ± standard deviation, 1.64±1.78 month; 113 boys and 87 girls) were included in this prospective study. The thickness of bilateral SCM muscles was measured by B-mode ultrasonography, and the stiffness of SCM muscles was measured in both the longitudinal and transverse sections, symmetrical and extensional supine position, by using strain and shear wave elastography. The correlation between thickness and elastic values of the SCM muscle and the following possible influential factors were evaluated: sex, different sides of SCM muscle, different ultrasonic sections and different infant positions. Results: Both sex and the side of SCM muscle did not show significant correlation with the thickness or stiffness of the SCM muscle (P > 0.05). The stiffness of SCM muscle in the longitudinal section was significantly greater than in the transverse section (P < 0.05). The measurements of the SCM muscle in the stretching position were significantly greater than those in the symmetrical position (P < 0.05). Conclusion: The stiffness of SCM measured by US elastography is affected by relative positions of the infants. Therefore, the factor should be taken into account when measuring the stiffness of SCM by US elastography. US elastography can evaluate the stiffness of SCM, which is helpful for clinical diagnosis and treatment of children with torticollis.
Background Peroral endoscopic myotomy (POEM) has been developed to provide a less-invasive myotomy for achalasia in adults but seldom has been used in pediatric patients. Objective To evaluate the ...feasibility, safety, and efficacy of POEM for pediatric patients with achalasia. Design Single-center, prospective study. Setting Academic medical center. Patients A total of 27 pediatric patients (mean age 13.8 years, range 6-17 years) with achalasia. Interventions POEM. Main Outcome Measurements The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤3. Secondary outcomes were procedure-related adverse events, clinical reflux adverse events, and lower esophageal sphincter (LES) pressure on manometry before and after POEM. Results A total of 26 cases (96.3%) underwent successful POEM. A submucosal tunnelling attempt failed in 1 case because of serious inflammation and adhesion. No serious adverse events related to POEM were encountered. During a mean follow-up period of 24.6 months (range 15-38 months), treatment success was achieved in all patients (mean score before vs after treatment 8.3 vs 0.7; P < .001). Mean LES pressure also decreased from a mean of 31.6 mm Hg to 12.9 mm Hg after POEM ( P < .001). Five patients developed clinical reflux adverse events (19.2%). Limitations Single center and lack of some objective evaluations. Conclusion This relatively long-term follow-up study adds to the evidence that POEM seems to be a promising new treatment for pediatric patients with achalasia, resulting in long-term symptom relief in all cases and without serious adverse events.
Histologically it is nearly impossible to distinguish the dedifferentiated component of dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone when the low-grade ...cartilaginous component is absent. Previous studies have revealed that isocitrate dehydrogenase 1 ( IDH1 ) and IDH2 mutations are present in a significant number of cartilaginous tumors including the majority of conventional chondrosarcoma and dedifferentiated chondrosarcomas. These mutations have not been studied in undifferentiated pleomorphic sarcomas of bone. We sought to investigate whether an IDH1 or IDH2 mutation signature could be used as a clinically diagnostic marker for the distinction of dedifferentiated component of chondrosarcoma from undifferentiated pleomorphic sarcoma of bone. Sixty-eight bone tumor cases, including 31 conventional chondrosarcomas, 23 dedifferentiated chondrosarcomas, and 14 undifferentiated pleomorphic sarcomas of bone, were collected for IDH1/2 mutation analysis either using the Qiagen IDH1/2 RGQ PCR Kit or using whole exome sequencing. IDH1/2 mutations were detected in 87% (20/23) of dedifferentiated chondrosarcomas and 30% (6/20) of conventional chondrosarcomas. No mutations were detected in the IDH1/2 codon 132 or codon 172 among 14 UPS of bone. Identification of IDH1 or IDH2 mutations supports the diagnosis of dedifferentiated chondrosarcoma rather than undifferentiated pleomorphic sarcoma of bone while also providing some insight into the pathogenesis of these two lesions.
Objective:
To evaluate whether this conversion rate to resectability could be increased when patients are treated with transarterial chemoembolization and hepatic arterial infusion chemotherapy ...(TACE-HAIC) using oxaliplatin plus fluorouracil/leucovorin.
Background:
Conventional TACE (c-TACE) is a common regimen for initially unresectable hepatocellular carcinoma (HCC), which converts to curative-intent resection in about 10% of those patients. It is urgent need to investigated better regimen for those patients.
Methods:
The data of 83 initially unresectable HCC patients were examined, including 41 patients in the TACE-HAIC group and 42 patients in the c-TACE group. Their response rate, conversion rate to resection, survival outcome, and adverse events were compared.
Results:
The conversion rate was significantly better in the TACE-HAIC group than in the c-TACE group (48.8% vs 9.5%;
P
< 0.001). The TACE-HAIC had marginal superiority in overall response rate as compared to c-TACE (14.6% vs 2.4%;
P
= 0.107 RECIST; 65.9% vs 16.7%;
P
< 0.001 mRECIST, respectively). The median progression-free survival was not available and 9.2 months for the TACE-HAIC and cTACE groups, respectively (hazard rate HR: 0.38; 95% confidence interval CI, 0.20–0.70;
P
= 0.003). The median overall survival was not available and 13.5 months for the TACE-HAIC and c-TACE groups, respectively (HR, 0.63; 95% CI, 0.34–1.17;
P
= 0.132). The 2 groups had similar rates of grade 3/4 adverse events (all
P
> 0.05).
Conclusions:
TACE-HAIC demonstrated a higher conversion rate and progression-free survival benefit than c-TACE and could be considered as a more effective regimen for patients with initially unresectable HCC. Future prospective randomized trials are needed to confirm it.
In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial ...chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population.
In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m
, leucovorin 400 mg/m
, fluorouracil bolus 400 mg/m
on day 1, and fluorouracil infusion 2,400 mg/m
for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment.
Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75;
< .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 46%
28 18%;
< .001) and a longer median progression-free survival (9.6 95% CI, 7.4 to 11.9
5.4 months 95% CI, 3.8 to 7.0,
< .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30%
19%,
= .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related.
FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.
Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is ...non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months 95% CI 3·5–6·3 vs 3·4 months 2·3–3·8; p=0·13). The most common adverse events were rash (81 41% of 200 patients in the icotinib group vs 98 49% of 199 patients in the gefitinib group) and diarrhoea (43 22% vs 58 29%). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 61% vs 140 70%; p=0·046), especially drug-related diarrhoea (37 19% vs 55 28%; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
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