B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer.

PURPOSE: The function of B cells in papillary thyroid cancer (PTC) is controversial. The role of B-cell-related tertiary lymphoid structures (TLSs) is still unclear. Whether B cells exert their anti-tumor effect through forming TLS in PTC needs further investigation. METHODS: We detected the percentage of B cells in PTC tissues by multi-parameter flow cytometry. Paraffin-embedded tumor tissues of 125 PTC patients were collected and stained with Haematoxylin-Eosin (H&E) for inflammatory infiltration analysis in combination with clinical features. Multiplexed immunohistochemistry (mIHC) was performed to verify the TLSs in above inflammatory infiltration. Correlation of B cells and TLSs with prognosis was analyzed using the TCGA database. RESULTS: We observed that PTC patients with higher expression of B lineage cell genes had improved survival and the percentage of B cells in the PTC tumor tissues was variable. Moreover, PTC tumor tissues with more B cells were surrounded by immune cell aggregates of varying sizes. We furtherly confirmed the immune cell aggregates as TLSs with different maturation stages. By analyzing PTC data from TCGA database, we found the maturation stages of TLSs were associated with genders and clinical stages among PTC patients. Moreover, patients with high TLSs survived longer and had a better prognosis. CONCLUSION: B cells are associated with the existence of TLSs which have different maturation stages in PTC. Both B cells and TLSs are associated with the survival rate of PTC. These observations indicate that the anti-tumor effects of B cells in PTC are associated with TLSs formation.

[Orbital cellulitis secondary to odontogenic superior maxillary sinus septum infection: a case report].

A 66-year-old woman presented with recurrent erythema, swelling and pain in her right eye. She had a history of extraction of the right upper second molar 5 months ago with subsequent development of an abscess which was incised and drained 4 months ago. Orbital CT scan revealed the formation of subperiosteal sinus cavity with an abscess in the right maxillary sinus and infraorbital foramen. The diagnosis was orbital honeycombing caused by odontogenic maxillary sinus septum infection. Utilizing the anterior lacrimal recess approach under nasal endoscope,incision and drainage of ocular abscess and debridement and drainage of right orbital abscess plus partial resection of the inner wall of the jaw were performed successfully with maxillary sinus septal drainage and maxillary sinus opening. The patient improved significantly after the operation.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

The Changing Landscape for the Treatment of Painful Spinal Metastases: is Stereotactic Body Radiation Therapy the New Standard of Care?

Due to advancements in systemic targeted and immunotherapies resulting in improved disease control and overall survival, and the increasing use of computed tomography and spine magnetic resonance imaging surveillance, the number of patients presenting with both asymptomatic and symptomatic spinal metastases is increasing. The need for versatile tumour ablative local management strategies, beyond the limits afforded by conventional palliative external beam radiation therapy (cEBRT), is increasingly more important. Stereotactic body radiation therapy (SBRT) was developed to meet such a need. This highly conformal technique allows the delivery of high biologically effective doses of radiation to the vertebral target, while controlling the differential dose exposure to the adjacent critical neural tissue. Identifying patients with painful spine metastases who would gain the most benefit from this important therapeutic option can be challenging. Here we summarise the randomised evidence specific to spine SBRT, comparing cEBRT with SBRT for pain control in patients with spine metastases in the palliative setting to better understand the role of spine SBRT in modern oncological spinal care.

Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set.

BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978.

HIF-1α repairs degenerative chondrocyte glycolytic metabolism by the transcriptional regulation of Runx2.

OBJECTIVE: HIF-1α and Runx2 expression usually increase in chondrocytes (CHs) during osteoarthritis (OA), which involves the changes in glycolytic metabolism. However, the molecular regulation of HIF-1α related to the CHs glycolytic metabolism is still unclear. In this study, we aimed to reveal the mediation of HIF-1α by Runx2 and its effect on the glycolytic metabolism of degenerative CHs. PATIENTS AND METHODS: The expression of HIF-1α, Runx2, and the degenerative markers of CHs in both natural conditions from the OA patients and IL-1ß treated in vitro model was analyzed by a Western blot or real-time polymerase chain reaction (RT-PCR). The glycolytic metabolism was determined by the intracellular glucose uptake and adenosine triphosphate (ATP) generation. Transfection of siRNA coding HIF-1α or Runx2 was used to clear the function between HIF-1α and Runx2 in the glycolytic metabolism of degenerated CHs caused by IL-1ß. Chromatin immunoprecipitation (ChIP) and Luciferase reporter gene assay were used to verify the Runx2 protein binds to the promoter of HIF-1α and promote its expression. RESULTS: HIF-1α and Runx2 were increased, and glucose uptake and ATP generation were decreased in the degenerative CHs from both OA and IL-1ß conditions. Under the stimulation of IL-1ß, Runx2 silencing rejected the upregulation of HIF-1α and further aggravated the glycolytic metabolism. When HIF-1α was silenced, the glycolytic metabolism of CHs was also suppressed. Besides, Runx2 protein could regulate HIF-1α expression in the transcriptional level by binding to its promoter. CONCLUSIONS: OHIF-1α plays a role in the self-repair of the glycolytic metabolism of degenerative CHs via the transcriptional regulation of Runx2.

Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence. PATIENTS AND METHODS: Cell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment. Blood was collected at pretreatment (T0), 3 weeks after initiation of paclitaxel (T1), between paclitaxel and anthracycline regimens (T2), or prior to surgery (T3). A personalized ctDNA test was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The median follow-up time for survival analysis was 4.8 years. RESULTS: At T0, 61 of 84 (73%) patients were ctDNA positive, which decreased over time (T1: 35%; T2: 14%; and T3: 9%). Patients who remained ctDNA positive at T1 were significantly more likely to have residual disease after NAC (83% non-pCR) compared with those who cleared ctDNA (52% non-pCR; odds ratio 4.33, P = 0.012). After NAC, all patients who achieved pCR were ctDNA negative (n = 17, 100%). For those who did not achieve pCR (n = 43), ctDNA-positive patients (14%) had a significantly increased risk of metastatic recurrence [hazard ratio (HR) 10.4; 95% confidence interval (CI) 2.3-46.6]; interestingly, patients who did not achieve pCR but were ctDNA negative (86%) had excellent outcome, similar to those who achieved pCR (HR 1.4; 95% CI 0.15-13.5). CONCLUSIONS: Lack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival.

[Analysis on clinical factors affecting transrectal natural orifice specimen extraction in rectal cancer surgery].

Objective: To identify the factors associated with successful transrectal specimen extraction after laparoscopic rectal cancer resection. Methods: A retrospective case-control study was conducted. Clinical data of rectal cancer patients who did or did not successfully undergo transrectal specimen extraction in Shanghai East Hospital between January 2017 and December 2017 were retrieved through the rectal cancer database of Shanghai East Hospital. Case inclusion criteria: (1) tumor size ≤7 cm by pelvic MRI; (2) body mass index (BMI)≤ 30 kg/m(2); (3) no history of neoadjuvant chemoradiotherapy; (4) no anal stenosis. Clinical data including age, gender, BMI, tumor obstruction, distance from tumor to anal verge, history of abdominal operation, maximal diameter of tumor and width of mesorectum in the anteroposterior dimension measured by pelvic MRI, etc. were collected. The χ(2) test was used to perform univariate analysis. Multivariate logistic regression was used to identify factors affecting transrectal specimen extraction. Results: A total of 208 patients were included in the analysis. Of 208 patients, 132 were men and 76 were women; mean age was (63±11) years old and median tumor size was 3.8 (IQR, 3.0 to 5.0) cm. Sixty-six (31.7%) patients completed transrectal specimen extraction successfully. Univariate analysis showed that patients who completed transrectal specimen extraction were more likely to have a lower BMI (χ(2)=7.420, P=0.006), be free from malignant obstruction (χ(2)=8.972, P=0.003), have a shorter distance from tumor to the anal verge (<5.0 cm) (χ(2)=14.960, P<0.001), a smaller tumor size (≤5.0 cm) (χ(2)=18.495, P<0.001) and a thinner mesorectum in the anteroposterior dimension (≤6.0 cm) (χ(2)=34.612, P<0.001) than those who failed to perform transrectal specimen extraction. Gender, age or history of abdominal operation were not associated with the successful extraction (all P>0.05). Multivariate analysis revealed that BMI ≤25.0 kg/m(2) (OR=2.32, 95% CI: 1.06 to 5.06, P=0.034), free from malignant obstruction (OR=3.01, 95% CI: 1.82 to 6.69, P<0.001), the distance from tumor to the anal verge <5.0 cm (OR=3.73, 95% CI: 1.22 to 11.43, P=0.021), tumor size ≤ 5.0 cm (OR=4.43, 95% CI: 1.39 to 14.09, P=0.012), and the anteroposterior width of mesorectum ≤ 6.0 cm (OR=4.30, 95% CI: 2.02 to 9.18, P<0.001) were independent protective factors for successful transrectal specimen extraction. Conclusion: Preoperative assessment of BMI, malignant obstruction, distance from tumor to the anal verge, tumor size and anteroposterior width of mesorectum is beneficial to choose appropriate patients with rectal cancer to undergo transrectal specimen extraction.

The benthic foraminiferal δ34S records flux and timing of paleo methane emissions.

In modern environments, pore water geochemistry and modelling simulations allow the study of methane (CH4) sources and sinks at any geographic location. However, reconstructing CH4 dynamics in geological records is challenging. Here, we show that the benthic foraminiferal δ34S can be used to reconstruct the flux (i.e., diffusive vs. advective) and timing of CH4 emissions in fossil records. We measured the δ34S of Cassidulina neoteretis specimens from selected samples collected at Vestnesa Ridge, a methane cold seep site in the Arctic Ocean. Our results show lower benthic foraminiferal δ34S values (∼20‰) in the sample characterized by seawater conditions, whereas higher values (∼25-27‰) were measured in deeper samples as a consequence of the presence of past sulphate-methane transition zones. The correlation between δ34S and the bulk benthic foraminiferal δ13C supports this interpretation, whereas the foraminiferal δ18O-δ34S correlation indicates CH4 advection at the studied site during the Early Holocene and the Younger-Dryas - post-Bølling. This study highlights the potential of the benthic foraminiferal δ34S as a novel tool to reconstruct the flux of CH4 emissions in geological records and to indirectly date fossil seeps.

Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA.

BACKGROUND: Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. PARTICIPANTS AND METHODS: The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. RESULTS: Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I-III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. CONCLUSIONS: cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.

Aluminum-26 chronology of dust coagulation and early solar system evolution.

Dust condensation and coagulation in the early solar system are the first steps toward forming the terrestrial planets, but the time scales of these processes remain poorly constrained. Through isotopic analysis of small Ca-Al-rich inclusions (CAIs) (30 to 100 µm in size) found in one of the most pristine chondrites, Allan Hills A77307 (CO3.0), for the short-lived 26Al-26Mg [t 1/2 = 0.72 million years (Ma)] system, we have identified two main populations of samples characterized by well-defined 26Al/27Al = 5.40 (±0.13) × 10-5 and 4.89 (±0.10) × 10-5. The result of the first population suggests a 50,000-year time scale between the condensation of micrometer-sized dust and formation of inclusions tens of micrometers in size. The 100,000-year time gap calculated from the above two 26Al/27Al ratios could also represent the duration for the Sun being a class I source.

Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study.

BACKGROUND: Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC. PATIENTS AND METHODS: Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival. RESULTS: All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9-31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9-34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0-2.2), and median overall survival was 18.0 months (95% CI 12.9-23.0). CONCLUSIONS: Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02447003.

Enhanced antigen presenting and T cell functions during late-phase allergic responses in the lung.

BACKGROUND: Allergic inflammation is a common feature of asthma and may contribute to both development and perpetuation of disease. The interaction of antigen-presenting cells (APC) with sensitized helper T lymphocytes (TC) producing Th2 cytokines may determine the inflammatory response. Recruitment of APC and TC to the lung during allergic responses has been demonstrated, but functional studies in humans have been limited. OBJECTIVE: This study examined the function of APC and TC accumulating at sites of inflammation after segmental allergen challenge (SAC). METHODS: Fifteen allergic patients underwent SAC, and cells from bronchoalveolar lavage (BAL) were collected after 24 hours. APC and TC from the blood and BAL were purified based on expression of the monocyte marker, CD14; the plasmacytoid dendritic cell (pDC) marker, BDCA4, identifying neuropilin-1 (NRP1); and the helper T cell marker, CD4. Functional activity was assessed using allergen-induced T cell proliferation. Flow cytometry identified cells expressing CD14 and NRP1. RESULTS: SAC resulted in a 12-fold increase in mononuclear cells having the morphologic appearance of blood monocytes. Most of these cells co-expressed CD14 and NRP1. After saline challenge, BAL mononuclear cells demonstrated little APC function. Following SAC, BAL mononuclear cells showed function equal to pDC from blood and greater than blood monocytes. Purified NRP1+ cells from BAL had even greater function than pDC cells from blood (P = .008). Using consistent sources of APC, enhanced proliferation of TC from lung compared to blood was also demonstrated (P = .002). CONCLUSIONS: The marked increase in APC function for allergen-specific TC proliferation during allergic inflammation is largely due to the recruitment of monocytes and dendritic cells. There is also an enhanced response in the lung TC population, consistent with recruitment of allergen-specific T cells. Interactions between recruited APC and TC may occur as an early event promoting allergic airway inflammation.

Modified Hepatic Venous Plane: A Key Factor for Improving Preoperative MDCT Donor Volume Prediction in Living-Donor Liver Transplantation.

OBJECTIVE: The aim of this work was to present our experience using a modified hepatic venous plane in multidetector computerized tomography (MDCT) for reducing the discrepancy between preoperative liver volume estimation and intraoperative weight (IOW) measurement in living-donor liver transplantation (LDLT). METHODS: We retrospectively reviewed the medical records of 57 consecutive living donors with the use of MDCT as a modality for volumetric assessment for LDLT from May 2007 to January 2015. We divided living donors into 2 groups according to surgical methods: right hepatectomy (RH) and left hepatectomy (LH). Initial liver volumetric measurement (group I) was assessed. After discussions with radiologist, the transplantation surgeon used a modified hepatic venous plane for surgical significant middle hepatic venous variants (>5 mm) in 16 living donors and applied the initial surgical plane in the remaining for the modified donor liver volumetric measurement (group II). We then compared the correlations of these 2 groups with the use of IOW. RESULTS: The overall correlation (r) between group I and IOW was 0.947. The correlations (r) between group I and IOW were 0.872 and 0.955 for RH and LH, respectively. Compared with group I, group II showed better correlation with IOW: r = 0.949 and 0.981 for RH and LH, respectively. The overall correlation (r) between group II and IOW was 0.980, and the error ratio was 5.95 ± 5.05%. CONCLUSIONS: Our study showed that using a modified hepatic venous plane in preoperative MDCT, after good communication between transplant surgeon and radiologist, can provide more accurate liver volume estimation and achieve a better correlation with IOW in LDLT.

[Effect of ginsenoside pre-treatment on 5-hydroxytryptamine system in SD rats with myocardial infarction and depression].

OBJECTIVE: To evaluate the effect of ginsenoside pre-treatment on serotonin (5-hydroxytryptamine, 5-HT), 5-HT2A receptor (5-HT2AR), and 5-HT transporter (serotonin transporter, SERT) in serum, platelet lysate and brain tissue homogenates in SD rats with myocardial infarction (MI) or depression. METHODS: Eighty SD rats were randomized treated with ginsenoside or normal saline(NS). After 4 weeks, the rats were, then, randomized to four subgroups: the MI, the depression, the MI in combination with depression and sham subgroups.5-HT, 5-HT2AR and SERT levels were detected in serum, platelet or brain. RESULTS: In the NS pre-treatment groups, serum 5-HT levels in sham rats (237.1±32.0) pg/ml were higher than in MI (58.0±11.6) pg/ml, depression (72.8±2.3) pg/ml, and MI with depression rats (62.5±10.2) pg/ml (all P=0.000). Pre-treatment of ginsenoside increased serum and platelet 5-HT in MI, depression and MI with depression rats compared with each corresponding NS treated subgroups (all P<0.005). However, treatment of ginsenoside lowered the 5-HT2AR expression in MI, depression, and MI with depression subgroups both in platelet and brain tissue homogenates compared with each corresponding NS treated subgroups (all P<0.05). As to SERT in platelet, treatment of ginsenoside increased its levels in depression rats (P=0.019), but lowered the levels in MI rats (P=0.001) compared with NS treated rats.There were no differences in brain 5-HT and SERT between ginsenoside and NS treated groups. CONCLUSIONS: The 5-HT system responses differently to ginsenoside treatment under different cardiac and mental stress conditions.Ginsenoside plays an important role in regulation of 5-HT system.

Genetic alterations and their clinical implications in older patients with acute myeloid leukemia.

A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.