Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. METHODS: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. RESULTS: Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009). CONCLUSIONS: Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction.

Thermally Processed Quantum-Dot Polypropylene Composite Color Converter Film for Displays.

Quantum dots (QDs) have attracted much attention as one of the most promising candidates for next-generation display materials. However, stability is still a big challenge for QDs. Herein, we encapsulated QDs in a thermoplastic polypropylene (PP) matrix by thermal processing technology to prepare a stabler color conversion film for the first time. Thermal processing technology expands the packaging materials of QDs from traditional soluble polymers to thermoplastic polymers such as PP with easy processing and a low cost. We showed that the QDs in the PP film exhibited longer-lasting stability than the traditional PMMA film. After 216 h of blue light accelerated aging test, the QDs maintained more than 90% of the initial performance in the PP film but dropped to less than 25% in the PMMA film. Moreover, the reasons for the improved stability have been further discussed. It was found that the PP-H film not only possessed better barriers to moisture and oxygen, but the absence of ester groups also led to a milder environment around the QDs. The results show that ester groups have stronger electronegativity and easily cause the ligands on the surface of QDs to fall off, which lead to performance degradation.

Pneumocystis jiroveci pneumonia after total hip arthroplasty in a dermatomyositis patient: A case report.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive therapy. In non-human immunodeficiency virus-infected patients, the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive treatments. The management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special care. CASE SUMMARY: We report a case of PJP in the perioperative period. A 61-year-old woman with a history of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis and interstitial pneumonia was administered with long-term oral methylprednisolone and cyclosporine. The patient underwent right total hip arthroplasty in the orthopaedic department for bilateral osteonecrosis of the femoral head. She was given intravenous drip hydrocortisone before anesthesia and on the first day after surgery and resumed oral methylprednisolone on the second postoperative day. On the fifth day after surgery, the patient suddenly developed dyspnea. The computed tomography scan showed diffuse grid shadows and ground glass shadows in both lungs. Polymerase chain reaction testing of bronchoalveolar lavage fluid was positive for Pneumocystis jiroveci. The patient was eventually diagnosed with PJP and was administered with oral trimethoprim-sulfamethoxazole. At the 6-mo review, there was no recurrence or progression. CONCLUSION: Continued perioperative glucocorticoid use in patients with anti-MDA5-positive dermatomyositis may increase the risk of PJP.

Acupuncture inhibits mammalian target of rapamycin, promotes autophagy and attenuates neurological deficits in a rat model of hemorrhagic stroke.

BACKGROUND: Intracerebral hemorrhage (ICH) accounts for approximately 15% of all stroke cases. Previous studies suggested that acupuncture may improve ICH-induced neurological deficits. Therefore, we investigated the effects of acupuncture on neurological deficits in an animal model of ICH. METHODS: Adult male Sprague-Dawley rats were injected with autologous blood (50 µL) into the right caudate nucleus. Additional rats underwent sham surgery as controls. ICH rats either received acupuncture (GV20 through GB7 on the side of the lesion) or sham acupuncture (1 cm to the right side of the traditional acupuncture point locations). Some ICH rats received acupuncture plus rapamycin injection into the right lateral ventricle. Neurological deficits in the various groups were assessed based on composite neurological score. The perihemorrhagic penumbra was analyzed by histopathology following hematoxylin-eosin staining. Levels of autophagy-related proteins light chain (LC)3 and p62 as well as of mammalian target of rapamycin (mTOR)-related proteins, and phosphorylated (p)-mTOR and p-S6K1 (ribosomal protein S6 kinase beta-1), were assessed by Western blotting. RESULTS: Acupuncture significantly improved composite neurological scores 7 days after ICH (17.7 ± 1.49 vs 14.8 ± 1.32, p < 0.01). Acupuncture augmented autophagosome and autolysosome accumulation based on transmission electron microscopy. Acupuncture significantly increased expression of LC3 (p < 0.01) but decreased expression of p62 (p < 0.01). Acupuncture also reduced levels of p-mTOR and p-S6K1 (both p < 0.01). CONCLUSION: Acupuncture improved neurological deficits in a rat model of ICH, possibly by inhibiting the mTOR pathway and activating autophagy.

Development of site-specific antibody-conjugated immunoliposomes for sensitive detection of disease biomarkers.

Liposome-based immunoassay (LIA) is an attractive protocol for amplifying the detection signals because of the excellent ability of liposomes to encapsulate signal marker compounds. The antigen-binding activity of the conjugated antibodies on the liposomal surface is crucial for the specificity and sensitivity of LIA. We present here a general platform to ensure that antibodies can conjugate onto the surface of liposomes in a site-specific and oriented manner. A His-handle-modified antibody with Fc region-specific and covalent conjugation was first fabricated using a photoactivatable ZBpa-His tag that was engineered using the aminoacyl-tRNA synthetase/suppressor tRNA technique. Based on the high affinity between the His tag and divalent metal ions, the novel His-modified antibody was oriented onto the surface of nickel ion-modified liposomes encapsulating horseradish peroxidase. With the prostate-specific antigen as a model, the detection efficiency of the new immunoliposomes was evaluated by chemiluminescence immunoassay. The immunoliposomes exhibited a limit of detection of 0.2 pg mL-1, which was a six time improvement compared with that of the chemical-coupled antibody-liposome conjugates. Thus, the proposed immunoliposomes are expected to hold potential applications for the sensitive detection of various biomarkers in complicated serum samples.

The Research on the Treatment of Metastatic Skin Cutaneous Melanoma by Huanglian Jiedu Decoction Based on the Analysis of Immune Infiltration Analysis.

OBJECTIVE: To explore the potential mechanism of Huanglian Jiedu Decoction (HJD) treatment and prevention of metastatic Cutaneous Melanoma (CM) occurrence and metastasis based on network pharmacological methods and immune infiltration analysis. METHODS: The GEO database was used to obtain metastatic CM disease targets, the TCMSP database and the HERB database were used to obtain HJD action targets, core genes were screened by protein interaction network, and the potential mechanism of HJD in the treatment of metastatic CM was explored by enrichment analysis, prognostic analysis and immune infiltration analysis. RESULTS: HJD treatment of metastatic CM involved 60 targets, enrichment analysis showed that HJD treatment of metastatic CM involved Chemokine signaling pathway, NF-kappa B signaling pathway, and Fluid shear stress and atherosclerosis, etc. Prognostic analysis revealed that HJD had a certain ability to improve the prognosis of metastatic CM patients. Immune infiltration analysis showed that HJD could inhibit the immune cell infiltration of metastatic CM patients by acting on related targets. CONCLUSIONS: Our study identified the potential mechanism of HJD in the treatment of metastatic CM through network pharmacology, and revealed the mechanism of HJD in the prevention of Skin Cutaneous Melanoma metastasis through immune infiltration analysis and prognostic analysis.

[Research Progress of FAM60A in the Regulation of Cellular Function].

FAM60A,a cell cycle protein,is a subunit of the SIN3 transcription regulator family member A/histone deacetylase(SIN3-HDAC)complex and plays an important role in cell cycle regulation,cell morphology change,cell proliferation,differentiation and migration,early embryogenesis and so on.Studies in recent years have shown that FAM60A plays a role in the occurrence and development of tumors including human osteosarcoma,esophageal cancer,gastric cancer,lung cancer and liver cancer,providing a new research direction for tumor diagnosis and treatment.Based on the research results in recent years at home and abroad,this paper discussed the effects of FAM60A on cellular functions.

Does new instrument for Oxford unicompartmental knee arthroplasty improve short-term clinical outcome and component alignment? A meta-analysis.

BACKGROUND: The Microplasty (MP) instrumentation designed for the Phase III Oxford mobile-bearing unicompartmental knee arthroplasty (UKA) system is considered a better option to achieve more accurate component positioning and alignment. In the present study, we focused on short-term clinical and radiological outcomes to determine whether the MP instrumentation can reduce the short-term revision rate and occurrence of outliers of metallic components. METHODS: The literature in PubMed, Embase, the Cochrane Library, and Web of Science was searched up to May 2020. Studies were scrutinized by two independent authors, and the revision rate, complication spectrum, and radiological assessment with outlier rates were specifically analyzed. RevMan 5.3 was used for the statistical analysis. RESULTS: Seven studies were included in the meta-analysis. Four studies reported both clinical and radiological outcomes, two reported only radiological outcomes, and one reported only clinical outcomes. The pooled analysis showed that the revision rate in the MP instrumentation group was 0.866 per 100 component years, while that in the control group was 1.124 (odds ratio, 0.77; p < 0.05). The subgroup analysis of the bearing dislocation rate showed a significantly greater reduction in the Korean population than in the populations of other countries (p < 0.05). The radiological assessment showed that the alignment of the femoral component was significantly improved (p < 0.05), while that of the tibial component was not (p > 0.05). CONCLUSION: The newly developed MP instrumentation for Oxford UKA significantly reduced the revision rate of this treatment. The positioning of the femoral component was also proven to be better by radiological assessments.

[Penetrative needling of scalp-points improves neurological function by promoting stem cell proli-feration and activating Shh/Gil1 signaling in intracerebral hemorrhage rats].

OBJECTIVE: To observe the effect of penetrative needling from "Baihui" (GV20) to "Qubin" (GB7) on neural stem cell proliferation and sonic hedgehog (Shh) signaling in subventricular zone (SVZ) in intracerebral hemorrhage (ICH) rats so as to explore its mechanisms underlying improvement of ischemic injury of brain. METHODS: Male SD rats were randomly divided into blank control, model, acupuncture and agonist (Purmorphamine, an activator of Shh signaling pathway) groups (n＝18 in each group, 6 for H．E. stain, 6 for examining neuronal cell proliferation, and 6 for immunohistochemistry). The ICH model was established by injecting autogenous blood (50 µL) into the right caudate nucleus. The neurological defect was scored with refe-rence to Bederson's method. Penetrative needling from GV20 to GB7 was performed by manipulating the needle for 6 min (repeated 3 times in 30 min), once daily for 7 days. Intraperitoneal injection of Purmorphamine (1 mg/mL, 1 mg/kg) was performed, once daily for 7 days. Histopathological changes of the hemorrhagic penumbra region were observed under microscope after H．E. stain, the newborn neural stem cell proliferation (BrdU＋/Nestin＋ double labeled cells) in the SVZ was observed by immunofluorescence after intraperitoneal injection of BrdU (50 mg/kg), and the expression of Shh and glioma-associated hemolog-1 (Gli1) detected by immunohistochemistry. RESULTS: After modeling, the neurological score and expression levels of Shh and Gil1 proteins were significantly increased in the model group relevant to the blank control group (P<0.001). Following the interventions, the neurological score was evidently decreased (P<0.05), while the number of BrdU＋/Nestin＋ double labeled cells and the expression levels of Shh and Gil1 proteins were significantly increased in both acupuncture and agonist groups in comparison with the model group (P<0.001). No significant differences were found between the acupuncture and agonist groups in down-regulating the neurological score and in up-regulating the number of BrdU＋/Nestin＋ double labeled cells and the expression of Shh and Gil1 proteins (P>0.05). Outcomes of H．E. stain showed obvious edema, disordered arrangement of cells, infiltration of inflammatory cells and red blood cells with glial cell hyperplasia around the hematoma area in the model group, which was relatively milder in both acupuncture and agonist groups such as in basic disappearance of edema and inflammatory reaction. CONCLUSION: Penetrative needling from GV20 to GB7 can obviously improve neurological function in ICH rats, which is related to its effects in activating Shh/Gil1 signaling and in further promoting neural stem cell proliferation in the SVZ region.

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease: a retrospective, cross-sectional study.

BACKGROUND: Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome. METHODS: Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis. RESULTS: A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P < 0.001). The percentage of AKI increased with age in the MCD patients. The percentage of AKI in patients aged 50 years or older was 52.9% (46/87), which was significantly higher than that [22.5% (63/280)] in patients under 50 years (χ2 = 6.347, P = 0.013). We observed statistically significant differences in age (43 [27, 59] years vs. 28 [20, 44] years, Z = 5.487, P < 0.001), male (78.0% vs. 51.4%, χ2 = 22.470, P < 0.001), serum albumin (19.9 ±â€Š6.1 g/L vs. 21.5 ±â€Š5.7 g/L, t = 2.376, P = 0.018), serum creatinine (129.5 [105.7, 171.1] µmol/L vs. 69.7 [57.7, 81.9] µmol/L, Z = 14.190, P < 0.001), serum urea (10.1 [6.2, 15.8] mmol/L vs. 4.7 [3.6, 6.4] mmol/L, Z = 10.545, P < 0.001), IgE (266.0 [86.7, 963.0] IU/ml vs. 142.0 [35.3, 516.5] IU/ml, Z = 2.742, P = 0.007), history of diabetes (6.4% vs. 1.2%, P = 0.009), and history of hypertension (23.9% vs. 5.1%, χ2 = 28.238, P < 0.001) between the AKI group and the non-AKI group. According to multivariate linear regression analysis, among the renal pathological features analyzed, renal tubular epithelial cell damage (ß = 178.010, 95% CI: 147.888-208.132, P < 0.001) and renal interstitial edema (ß = 28.833, 95% CI: 11.966-45.700, P = 0.001) correlated with serum creatinine values. CONCLUSIONS: The percentage of AKI in MCD patients is significantly higher than that in MN patients. Patients over 50 years old are more likely to develop AKI. Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.

Clinical Features and Prognosis of Crohn's Disease with Upper Gastrointestinal Tract Phenotype in Chinese Patients.

BACKGROUND: The epidemiology of upper gastrointestinal (L4) Crohn's disease in China remains poorly characterized. AIMS: We aimed to identify the clinical characteristics of L4 disease and clarify the relationship between disease characteristics at diagnosis and early outcomes. METHODS: We retrospectively enrolled 246 patients diagnosed between 2013 and 2017 and followed up for > 1 year post-diagnosis. Primary outcomes included the 1-year rates of hospitalization and abdominal surgery according to disease location and behavior. RESULTS: Of 80 patients with L4 disease (61, 25, and 18 with esophagogastroduodenal, jejunal, and proximal ileal involvement, respectively), none had granuloma, whereas 66.7%, 50%, 46.9%, 75%, and 70% had disease-specific endoscopic lesions in the esophagus, stomach, duodenum, jejunum, and proximal ileum, respectively. Compared to non-L4 disease, L4 disease was associated with higher rates of abdominal surgery (41.3% vs. 11.4%, P < 0.001) but similar rates of hospitalization within 1 year post-diagnosis. In L4 disease, jejunal and proximal ileal involvement was associated with stricturing behavior (P = 0.034, P < 0.001) and higher abdominal surgery rate (both: P < 0.001). Risk factors for abdominal surgery within 1 year post-diagnosis included age ≥ 40 years (OR 1.920; 95% CI 1.095-3.367), L4 phenotype (OR 6.335; 95% CI 3.862-10.390), stricturing disease (OR 3.162; 95% CI 1.103-9.866), and penetrating disease (OR 11.504; 95% CI 3.409-38.825), whereas the protective factor was female sex (OR 0.214; 95% CI 0.123-0.373). CONCLUSIONS: Early outcomes are worse for L4 than for non-L4 disease. Jejunoileum involvement predicts stricturing disease and early surgery. More aggressive initial therapy is needed to improve L4-disease prognosis.

[Controlling the spatiotemporal expression of germ line specific genes by PRC1.6 complex].

Polycomb repressive complex 1 (PRC1) is a class of epigenetic regulatory complexes that normally represses gene expression by catalyzing and/or recognizing chromatin modifications. PRC1 mainly functions in stem cell maintenance, cell differentiation, cell cycle regulation and related processes. PRC1 also have aberrant functions which has been implicated in many types of developmental diseases and cancers. Mammalian PRC1 complexes are divided into six subtypes based on their composition and function; subtypes include PRC1.1 to PRC1.6. Each PRC1 subtype regulates a unique collection of target genes. The PRC1.6 complex subtype plays key roles in specifically repressing transcription of genes controlling germ cell development in embryonic stem cells and other somatic cell types. Recent research demonstrates that the PRC1.6 complex is also crucial for the timely activation of the germ line of specific genes during spermatogenesis, which is essential for proper gonad development. In this review, we summarize the identification of molecular functions of each core component of the PRC1.6 complex including how it recognizes and represses germ line specific genes. We also update the biological roles of this complex in regulating the spatiotemporal expression of germ line specific genes during embryonic development, gonad development, and spermatogenesis. Lastly, the crosstalk between the PRC1.6 complex and the other main epigenetic regulatory mechanisms involved in controlling spermatogenesis is discussed. Our discussion of the PRC1.6 complex in regulating germ line specific genes informs the studies of molecular processes of spermatogenesis and contributes to the understanding of the pathogenic mechanisms of male infertility.

Chiral CdSe nanoplatelets as an ultrasensitive probe for lead ion sensing.

As opposed to traditional photoluminescence and ultra-violet based optical sensing, we present here a sensing system based on resolved optically active polarization with promising applications. It is based on the ultrathin CdSe nanoplatelets (NPLs) when modified with either l or d-cysteine molecules (l/d-cys) as bio-to-nano ligands. The chiral ligand transfers its chiroptical activity to the achiral nanoplatelets with an anisotropy factor of ∼10-4, which unlocks the chiral excitonic transitions and allows lead ion detection with a limit of detection (LOD) as low as 4.9 nM. Simulations and modelling based on time-dependent density functional theory (TD-DFT) reveal the chiral mechanism of l/d-cys capped CdSe NPLs. The presented CD-based sensing system illustrates an alternative possibility of using chiral CdSe NPLs as competitive chiral sensors for heavy metal ion detection.

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture inhibits apoptosis in the perihemorrhagic penumbra.

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage. However, there is no research showing the relationship between this treatment and cell apoptosis. Rat models of intracerebral hemorrhage were established by injecting 60 µL of autologous blood into the right side of the caudate-putamen. Six hours later, the needle traveled subcutaneously from the Baihui acupoint to Qubin acupoint. The needle was alternately rotated (180 ± 10 turns/min) manually along clockwise and counter-clockwise directions. Stimulation lasted for 7 days, and was performed three times each for 6 minutes with 6-minute intervals between stimulations. Rats intraperitoneally receiving Sonic hedgehog pathway activator, purmorphamine (1 mg/kg per day), served as positive controls. Motor and sensory function were assessed using the Ludmila Belayev test. Extent of pathological changes were measured in the perihemorrhagic penumbra using hematoxylin-eosin staining. Apoptosis was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Expression of smoothened (Smo) and glioma-associated homolog 1 (Gli1) was determined by western blot assay. Our results showed that Baihui-penetrating-Qubin acupuncture promoted recovery of motor and sensory function, reduced the apoptotic cell percentage in the perihemorrhagic penumbra, and up-regulated Smo and Gli1 expression. We conclude that Baihui-penetrating-Qubin acupuncture can mitigate hemorrhage and promote functional recovery of the brain in a rat model of intracerebral hemorrhage, possibly by activating the Sonic hedgehog pathway.

Glasgow Prognostic Score is superior to ECOG PS as a prognostic factor in patients with gastric cancer with peritoneal seeding.

The Glasgow Prognostic Score (GPS) has been shown to be associated with survival rates in patients with advanced cancer. The present study aimed to compare the GPS with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in patients with gastric cancer with peritoneal seeding. For the investigation, a total of 384 gastric patients with peritoneal metastasis were retrospectively analyzed. Patients with elevated C-reactive protein (CRP; >10 mg/l) and hypoalbuminemia (<35 mg/l) were assigned a score of 2. Patients were assigned a score of 1 if presenting with only one of these abnormalities, and a score of 0 if neither of these abnormalities were present. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal seeding were analyzed. The results showed that the median overall survival (OS) of patients in the GPS 0 group was longer, compared with that in the GPS 1 and GPS 2 groups (15.50, vs. 10.07 and 7.97 months, respectively; P<0.001). No significant difference was found between the median OS of patients with a good performance status (ECOG <2) and those with a poor (ECOG ≥2) performance status (13.67, vs. 11.80 months; P=0.076). In the subgroup analysis, the median OS in the GPS 0 group was significantly longer, compared with that in the GPS 1 and GPS 2 groups, for the patients receiving palliative chemotherapy and patients without palliative chemotherapy. Multivariate survival analysis demonstrated that CA19-9, palliative gastrectomy, first-line chemotherapy and GPS were the prognostic factors predicting OS. In conclusion, the GPS was superior to the subjective assessment of ECOG PS as a prognostic factor in predicting the outcome of gastric cancer with peritoneal seeding.

Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy.

The role of palliative surgery is controversial in advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitors (TKIs) therapy.We evaluated safety and clinical outcomes in a single institution series of advanced GIST patients from January 2002 to December 2008.One hundred and fifty-six patients had been recruited, including 87 patients underwent surgical resection and 69 patients kept on TKIs treatment. Four patients had major surgical complications. Median follow-up was 38.3 months, the overall survival (OS) and progression-free survival (PFS) of the patients in surgical group were longer than the nonsurgical group, PFS: 46.1 versus 33.8 months (P < .01), OS: 54.8 versus 40.4 months. In the subgroup analysis for the patients received surgery, the median PFS for patients with progression disease, stable disease, and partial response was 33.3, 51.5, and 83.0 months, respectively (P < .01). Median OS was 68.0 months in those with only liver or peritoneal metastases, and 45.3 months in those with both metastases. Median PFS of patients underwent R0/R1 resection was 73.6 months compared with 35.8 months in R2 resection patients (P < .01).Patients with advanced GISTs have prolonged OS after debulking procedures. Surgery for patients who have responsive disease after TKIs treatment should be considered.

Can therapeutic drug monitoring increase the safety of Imatinib in GIST patients?

Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin ) with adverse effects (AEs) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI. The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 ± 598.6 ng/mL and 242.1 ng/mL, respectively, which were significantly higher than those in patients who did not (1327.2 ± 623.4 ng/mL, P = 1.75 × 10-4 ; 206.3 ng/mL, P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/mL with ROCAUC (95%CI) of 0.693 (0.597-0.789) and 207.1 ng/mL with ROCAUC (95%CI) of 0.646 (0.546-0.745), respectively. Multivariate regression confirmed the correlation of Imatinib Cmin with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients.

Silicotuberculosis with oesophagobronchial fistulas and broncholithiasis: a case report.

A 76-year-old woman was admitted to the hospital four times from November 2007 to June 2009. In this complex case, the patient had silicosis complicated by broncholithiasis, oesophagobronchial fistulas, and relapsed tuberculosis. She had worked as a stone crusher for 3 years and was exposed to a large amount of quartz dust. Barium oesophagography, gastroesophageal endoscopy, and biopsy suggested oesophageal-related chronic inflammation and ulceration, which may have caused the repeated oesophagobronchial fistulas. Bronchoscopy revealed a free broncholithiasis in the left mainstem bronchus. The patient was admitted a fourth time because of silicotuberculosis relapse. After 9 months of antituberculosis treatment, the patient recovered and was still clinically well at the time of this writing.