Development and validation of a preoperative CT-based radiomic nomogram to predict pathology invasiveness in patients with a solitary pulmonary nodule: a machine learning approach, multicenter, diagnostic study.

OBJECTIVES: To develop and validate a preoperative CT-based nomogram combined with radiomic and clinical-radiological signatures to distinguish preinvasive lesions from pulmonary invasive lesions. METHODS: This was a retrospective, diagnostic study conducted from August 1, 2018, to May 1, 2020, at three centers. Patients with a solitary pulmonary nodule were enrolled in the GDPH center and were divided into two groups (7:3) randomly: development (n = 149) and internal validation (n = 54). The SYSMH center and the ZSLC Center formed an external validation cohort of 170 patients. The least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression analysis were used to feature signatures and transform them into models. RESULTS: The study comprised 373 individuals from three independent centers (female: 225/373, 60.3%; median [IQR] age, 57.0 [48.0-65.0] years). The AUCs for the combined radiomic signature selected from the nodular area and the perinodular area were 0.93, 0.91, and 0.90 in the three cohorts. The nomogram combining the clinical and combined radiomic signatures could accurately predict interstitial invasion in patients with a solitary pulmonary nodule (AUC, 0.94, 0.90, 0.92) in the three cohorts, respectively. The radiomic nomogram outperformed any clinical or radiomic signature in terms of clinical predictive abilities, according to a decision curve analysis and the Akaike information criteria. CONCLUSIONS: This study demonstrated that a nomogram constructed by identified clinical-radiological signatures and combined radiomic signatures has the potential to precisely predict pathology invasiveness. KEY POINTS: • The radiomic signature from the perinodular area has the potential to predict pathology invasiveness of the solitary pulmonary nodule. • The new radiomic nomogram was useful in clinical decision-making associated with personalized surgical intervention and therapeutic regimen selection in patients with early-stage non-small-cell lung cancer.

Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study.

BACKGROUND: Preoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs. METHODS: We retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded. RESULTS: A total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%. CONCLUSION: Preoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.

Identification of upstream miRNAs of SNAI2 and their influence on the metastasis of gastrointestinal stromal tumors.

BACKGROUND: SNAI2, a member of the snail zinc finger protein family, plays an important role in the metastasis of several types of carcinoma. OBJECTIVE: This study aims to investigate the upstream miRNAs of SNAI2 and their influence on the metastasis of gastrointestinal stromal tumors (GISTs). METHODS: The expression levels of SNAI2, CDH1, and CDH2 in GISTs were determined by immunohistochemistry, and the correlations with their clinicopathologic characteristics were analyzed. Subsequently, the miRNAs involved in regulating SNAI2 expression were predicted by bioinformatics technique, screened by miRNA microarray tests, and verified by real-time PCR, dual luciferase reporter assay, and invasion assay. The influence of SNAI2 and miRNAs on the invasive ability of the GIST cells and the related mechanism were detected. OUTCOMES: SNAI2 expression significantly increased and CDH1 expression markedly decreased in the cases of GISTs with distant metastasis. Silencing of the SNAI2 gene impaired the invasiveness of GIST cells in vitro. MiR-200b-3p, miR-30c-1-3P, and miR-363-3P were verified as the upstream metastasis-associated miRNAs of SNAI2 in GISTs by miRNA microarray, real-time PCR, dual luciferase reporter assay, and invasion assay. They bound to the 3'-UTR of SNAI2, downregulated SNAI2 expression, and inhibited the invasiveness of GIST cells. SNAI2 targetedly bound to the promoter of the CDH1 gene, downregulated the expression of CDH1, and contributed to the metastasis of GISTs. CONCLUSION: SNAI2 and CDH1 correlated with the metastasis of GISTs, and silencing of the SNAI2 gene impaired the invasiveness of GIST cells. MiR-200b-3p, miR-30c-1-3P, and miR-363-3P contribute to the metastasis of GISTs in vitro by mediating the SNAI2/CDH1 axis. SNAI2 may be a potential target for the treatment of GISTs in the future.

MiR-137 regulates epithelial-mesenchymal transition in gastrointestinal stromal tumor.

Activation of the epithelial-to-mesenchymal transition (EMT) endows extraordinary invasive capability of cancer cells and causes of treatment failure and metastasis in gastrointestinal stromal tumor (GIST); however, the molecular mechanisms governing GIST invasion remain largely unknown. MicroRNAs (miRNAs) have been shown to play critical roles in cell motility and invasion, which promotes us to study the biological functions of miR-137 in the EMT of GIST. We have found that miR-137 was dramatically downregulated in clinical specimen of GIST. Using an in silico analysis approach, Twist1, a key regulator gene of EMT, has been identified as the target of miR-137. Quantitative RT-PCT and western blot were used to confirm that miR-137 directly targeted on Twist1 and repressed Twist1 expression in GIST-H1 human gastrointestinal stromal tumor cell line. Further, miR-137 was found to increase expression of E-cadherin and cytokeratin, but suppress expression of N-cadherin and vimentin. In vitro experiments have shown that miR-137 enhanced the epithelial cell morphology, decreased GIST cell migration, activated G1 cell cycle arrest, and induced cell apoptosis. These results suggest a novel mechanism that miR-137 regulates EMT and inhibits cell migration via Twist1 downregulation. Therefore, miR-137 may function as anti-migration and anti-metastasis in GIST and our study provides a potential approach for developing miR-137-based therapeutic strategy for GIST.

Treatment strategy of rectal gastrointestinal stromal tumor (GIST).

BACKGROUND: Rectal gastrointestinal stromal tumor (GIST) is a rare entity. A retrospective analysis of outcomes from a single institution to identify treatment strategies associated with improved outcomes. METHODS: Records of patients with GIST of the rectum were retrospectively reviewed. Patient and tumor characteristics, treatment details, and outcome were evaluated. RESULTS: Compared with the trans-abdominal approach group, the local excision group patients had smaller size and lower location tumors (P < 0.05). Positive resection margin was an important hazard factor for DFS (OR, 7.63; P = 0.015). Among the patients with the tumor size >5 cm, those with preoperative Imatinib therapy had higher rate of a negative resection margin than those without (100% vs. 20%, P = 0.048). Among the patients with intermediate and high-risk tumors, those who received peri-operative Imatinib therapy had longer DFS compared with those without (61.3 ± 6.1 months vs. 20.2 ± 4.4 months, P = 0.030). CONCLUSIONS: The location of rectal GIST impacts the choice of resection type. Most patients with tumors within 5 cm of the anal verge can be treated with local excision. Positive resection margin is the independent hazard factor for poorer survival. Peri-operative Imatinib therapy is associated with a prolonged DFS in patients with intermediate and high-risk tumors.

Efficiency assessment of intelligent patient-specific instrumentation in total knee arthroplasty: a prospective randomized controlled trial.

BACKGROUND: In total knee arthroplasty (TKA), the practical use of patient-specific instrumentation (PSI) has been reported previously with both advantage and disadvantage. The application of artificial intelligent (AI) forces overwhelmingly development of medical industries, while the impact of AI on PSI efficiency remains unknown. Thus, this study aimed to assess the efficiency of Intelligent-PSI (i-PSI) in TKA, compared with the conventional instrumentation-TKA (CI). METHODS: 102 late-stage OA patients who met inclusive criteria were recruited in this prospective randomized controlled trial and separated into two groups (i-PSI vs. CI). In both groups, an AI preoperative planning engine was applied for surgery decision making. In CI group, conventional instrumentation was applied for bony resection, while resection of i-PSI group was completed with i-PSI. A convolutional neural network was applied to automatically process computer tomography images and thus produced i-PSI. With the help of three-dimension printing, the workflow of production was largely simplified. AI-driven preoperative planning guided resection and alignment decisions. Resection measurement, perioperative radiography and perioperative clinical outcomes were analyzed to verify efficiency of i-PSI. RESULTS: In resection outcomes, smaller deviation of lateral and medial distal femoral resection were found in i-PSI group than CI group (P = 0.032 and 0.035), while no difference was found in other resection planes. In radiography outcomes, postoperative coronal alignments of i-PSI group, including postoperative Hip-knee-ankle axis (HKA) (P = 0.025), postoperative HKA outliners (P = 0.042), Femoral coronal alignment (FCA) (P = 0.019) and Joint line convergence angle (JLCA) (P = 0.043) showed closer to neutral position than CI group. Moreover, Femoral sagittal alignment (FSA) of i-PSI group showed closer to neutral position than CI group(P = 0.005). No difference was found in other alignments. In clinical outcomes, i-PSI group seemed to cost more surgical time than CI group (P = 0.027), while others showed no differences between the two groups. CONCLUSION: Intelligent Patient-specific Instrumentation in TKA achieved simplified production flow than conventional PSI, while also showed more accurate resection, improved synthesis position and limb alignment than conventional instrumentation. Above all, this study proved that i-PSI being an applicable and promising tool in TKA.

The necessity of indwelling gastrointestinal decompression after gastrectomy: a meta-analysis.

BACKGROUND: This meta-analysis was designed to evaluate the necessity of indwelling gastrointestinal decompression after gastrectomy. METHODS: Medline, Embase, and the Cochrane Library were searched. We identified randomized controlled trials that compared individuals with or without gastrointestinal decompression after gastrectomy, and a meta-analysis was performed on data regarding the recovery time of gastrointestinal function, length of hospital stay, complications, and mortality using fixed effect and random effect models. RESULTS: Eight randomized controlled trials that had enrolled 975 patients were included in the present study. The difference in the interval to oral intake (weighted mean difference 0.56, 95% confidence interval [CI] 0.16-0.96, P = 0.006) between the decompression group and nondecompression group was significant, but no significant differences were found in the interval to flatus (weighted mean difference 0.24, 95% CI -0.13 to 0.61, P = 0.20) or length of hospital stay (weighted mean difference 1.04, 95% CI -0.05 to 2.14, P = 0.06). Additionally, no significant differences were found in complications, including nausea or vomiting (odds ratio [OR] 1.23, 95% CI 0.57-2.65, P = 0.59), fever (OR 1.55, 95% CI 0.96-2.51, P = 0.07), pulmonary complications (OR 1.41, 95% CI 0.82-2.43, P = 0.22), anastomotic leakage (OR 1.15, 95% CI 0.55-2.40, P = 0.70), paralytic ileus or small bowel obstruction (OR 1.80, 95% CI 0.57-5.70, P = 0.32), intra-abdominal abscess (OR 1.08, 95% CI 0.50-2.34, P = 0.84), wound infection (OR 1.29, 95% CI 0.56-2.96, P = 0.55), or wound dehiscence (OR 1.47, 95% CI 0.43-4.95, P = 0.54) between the two groups. A sensitivity analysis of the pooled data from high-quality studies and studies with >20 cases per group showed that the length of hospital stay was prolonged significantly in the decompression group compared with the nondecompression group. CONCLUSIONS: Routine gastrointestinal decompression after gastrectomy does not promote the recovery of gastrointestinal function or reduce the incidence of postoperative complications. In our series, decompression was correlated with a prolonged interval to oral intake, a longer duration of hospitalization, and increased patient discomfort.

Medial versus lateral approach in laparoscopic colorectal resection: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of the medial approach (MA) and the lateral approach (LA) in the treatment of colorectal disease. METHODS: Studies published since 1994 that compared MA versus LA in laparoscopic colorectal resection were collected. Data on conversion rate, operative time, blood loss, number of harvested lymph nodes, hospital stay, complications, mortality, rate of recurrence, and hospitalization costs for MA and LA were meta-analyzed using fixed-effect and random-effect models. RESULTS: Five cohort studies (2 randomized controlled trials and 3 retrospective studies) that included 881 patients were studied. Of these patients, 475 and 582 had undergone laparoscopic colorectal resection via MA and LA, respectively. There were significant reductions in conversion rate and operative time and possible reductions in blood loss and hospitalization costs for MA compared to LA; however, there were fewer harvested lymph nodes for MA compared with LA, which remains to be further studied. Other outcome variables such as postoperative complications, postoperative immune function, mortality, and rate of recurrence were not found to be statistically significant for either group. Sensitivity analysis on the pooled data from randomized controlled trials showed that the conversion rates were not significantly different between MA and LA. CONCLUSIONS: Compared with the lateral approach, the medial approach has the advantages of shorter operative time and possibly lower conversion rate; it also can be as safe as the lateral approach. Whether the MA has less blood loss and lower hospitalization costs remains to be confirmed, and its oncological safety and long-term prognosis are not clear. Due to insufficient data from a limited number of studies, inadequate assessment of the results may arise.

Pretreatment radiomic biomarker for immunotherapy responder prediction in stage IB-IV NSCLC (LCDigital-IO Study): a multicenter retrospective study.

BACKGROUND: The predictive efficacy of current biomarker of immune checkpoint inhibitors (ICIs) is not sufficient. This study investigated the causality between radiomic biomarkers and immunotherapy response status in patients with stage IB-IV non-small cell lung cancer (NSCLC), including its biological context for ICIs treatment response prediction. METHODS: CT images from 319 patients with pretreatment NSCLC receiving immunotherapy between January 2015 and November 2021 were retrospectively collected and composed a discovery (n=214), independent validation (n=54), and external test cohort (n=51). A set of 851 features was extracted from tumorous and peritumoral volumes of interest (VOIs). The reference standard is the durable clinical benefit (DCB, sustained disease control for more than 6 months assessed via radiological evaluation). The predictive value of combined radiomic signature (CRS) for pathological response was subsequently assessed in another cohort of 98 patients with resectable NSCLC receiving ICIs preoperatively. The association between radiomic features and tumor immune landscape on the online data set (n=60) was also examined. A model combining clinical predictor and radiomic signatures was constructed to improve performance further. RESULTS: CRS discriminated DCB and non-DCB patients well in the training and validation cohorts with an area under the curve (AUC) of 0.82, 95% CI: 0.75 to 0.88, and 0.75, 95% CI: 0.64 to 0.87, respectively. In this study, the predictive value of CRS was better than programmed cell death ligand-1 (PD-L1) expression (AUC of PD-L1 subset: 0.59, 95% CI: 0.50 to 0.69) or clinical model (AUC: 0.66, 95% CI: 0.51 to 0.81). After combining the clinical signature with CRS, the predictive performance improved further with an AUC of 0.837, 0.790 and 0.781 in training, validation and D2 cohorts, respectively. When predicting pathological response, CRS divided patients into a major pathological response (MPR) and non-MPR group (AUC: 0.76, 95% CI: 0.67 to 0.81). Moreover, CRS showed a promising stratification ability on overall survival (HR: 0.49, 95% CI: 0.27 to 0.89; p=0.020) and progression-free survival (HR: 0.43, 95% CI: 0.26 to 0.74; p=0.002). CONCLUSION: By analyzing both tumorous and peritumoral regions of CT images in a radiomic strategy, we developed a non-invasive biomarker for distinguishing responders of ICIs therapy and stratifying their survival outcome efficiently, which may support the clinical decisions on the use of ICIs in advanced as well as patients with resectable NSCLC.

Meta-analysis of laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for gastric cancer.

BACKGROUND: To assess the value of laparoscopy-assisted distal gastrectomy with D2 dissection for treatment of gastric cancer. METHODS: We collected studies that have compared laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 dissection for treatment of gastric cancer in the past 15 years. Data of interest for LADG and ODG were subjected to meta-analysis using a fixed-effect and random-effect model. RESULTS: We analyzed 8 studies that included 1,065 patients. There were significant differences in operating time, blood loss, time to first flatus and first eating, postoperative hospital stay, and postoperative complications between the LADG and ODG groups. Compared with the ODG group, blood loss and complications in the LADG group decreased, time to recovery of gastrointestinal function and hospitalization period were shorter, but operating time was longer. There were no significant differences in the number of harvested lymph nodes, mortality, and rate of recurrence between the groups. CONCLUSIONS: Compared with ODG, LADG with D2 dissection has the advantages of minimal invasion, faster recovery, and fewer complications, and it can achieve the same degree of radicality and short-term prognosis as ODG. The drawbacks are that the operating time is slightly longer and long-term prognosis is not clear.

Expression and significance of twist, E-cadherin, and N-cadherin in gastrointestinal stromal tumors.

BACKGROUND: Twist, a basic helix-loop-helix transcription factor, has been reported to play a key role in the metastatic progression of several types of cancer. AIMS: To investigate the expression and clinical significance of Twist, E-cadherin, and N-cadherin in gastrointestinal stromal tumors (GISTs). METHODS: The expression of Twist, E-cadherin, and N-cadherin in GISTs was determined by immunohistochemistry, and their relationship with clinicopathological characteristics was analyzed. RESULTS: The positive rates of Twist, E-cadherin, and N-cadherin in GISTs were 66.7 % (52/78), 35.9 % (28/78), and 75.6 % (59/78), respectively. Twist was expressed significantly more in GISTs with distant metastasis or local invasion (p < 0.05). Although E-cadherin was expressed significantly less in cases of GISTs with distant metastasis (p < 0.05), expression of N-cadherin did not differ significantly according to clinical and pathological characteristics (p > 0.05). Expression of Twist was correlated positively with E-cadherin (rs = -0.253, p = 0.026) and negatively with N-cadherin (rs = 0.245, p = 0.030). CONCLUSIONS: Twist was expressed significantly more and E-cadherin significantly less in GISTs with metastasis, and expression of both was closely related to metastasis of GISTs.

[Expression and significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors].

OBJECTIVE: To explore the expression and clinical significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors (GIST). METHODS: Seventy eight GIST specimens removed surgically from 2004 to 2007 were collected from the Department of Gastrointestinal Surgery at Guizhou Provincial People's Hospital. There were 48 males and 30 females with an age range of 28 - 87 years old. The expressions of Slug, E-cadherin and N-cadherin in GIST were determined by immunohistochemistry. And the correlations with their clinicopathologic characteristics were analyzed. RESULTS: The positive rates of Slug, E-cadherin and N-cadherin in GIST were 53.8% (42/78), 35.9% (28/78) and 75.6% (59/78) respectively. And the differences were statistically significant (χ(2) = 24.98, P < 0.05). Slug was expressed markedly higher in the cases of GIST with distant metastasis or distant metastasis and local invasion: 75% (18/24) vs 44.4% (24/54), 63.6% (28/44) vs 41.2% (14/34), both P < 0.05. And E-cadherin was expressed markedly lower in the cases of GIST with distant metastasis: 16.7% (4/24) vs 44.4% (24/54), P < 0.05. The expression of N-cadherin was not significantly different between its clinicopathological characteristics (allP > 0.05). The expression of Slug correlated negatively with that of E-cadherin (r(s) = -0.267, P = 0.018). But it had no correlation with that of N-cadherin (r(s) = 0.056, P = 0.625). CONCLUSION: Slug is expressed markedly higher while E-cadherin markedly lower in metastatic GIST, and both are closely correlated with the metastasis of GIST.

Preoperative CT-based peritumoral and tumoral radiomic features prediction for tumor spread through air spaces in clinical stage I lung adenocarcinoma.

OBJECTIVES: This study aims to develop and evaluate preoperative CT-based peritumoral and tumoral radiomic features to predict tumor spread through air space (STAS) status in clinical stage I lung adenocarcinoma (LUAD). MATERIALS AND METHODS: From June 2018 to December 2019, a retrospective diagnostic investigation was done. Patients with pathologically confirmed STAS status (N = 256) were eventually enrolled. The development cohort consisted of 191 patients (74.6%) chosen randomly in a 7:3 ratio, whereas the validation group consisted of 65 patients (25.4%). The performance of models was assessed using receiver operating characteristic analysis, accuracy, sensitivity, specificity, negative predictive values, and positive predictive values. RESULTS: The STAS positive status was found in 85 (33.2%) of the 256 patients (female: 53.2%; median [IQR] age: 62.0, [53.0-79.0] years), while the STAS negative status was found in 171 patients (66.8%) (female:50.6%; median [IQR] age: 62.0, [53.0-87.0] years). The combined TRS and PRS-15 mm model had an AUC of 0.854 (95% CI, 0.799-0.909) in the development cohort and 0.870 (95% CI, 0.781-0.958) in the validation cohort, indicating that the tumor radiomic signature (TRS) model and different peritumoral radiomic signature (PRS) models were used to build the optimal gross radiomic signature (GRS) model. The radiomic nomogram achieves superior discriminatory performance than GRS and clinical and radiological signatures (CRS), with an AUC of 0.871 (95% CI, 0.820-0.922) in the development cohort and AUC of 0.869 (95% CI, 0.776-0.961) in the validation cohort. Based on the Akaike information criterion (AIC) and decision curve analysis (DCA), the radiomic nomogram provided greater clinical predictive capacity than clinical or any radiomic signatures alone. CONCLUSION: In conclusion, we discovered that peritumoral characteristics were substantially related to STAS status. This study revealed the unit of radiomic signature and clinical signatures may have a better performance in STAS status.

Clinicopathologic Characteristics and Prognosis of PDGFRA-Mutant Gastrointestinal Stromal Tumors: A Large-Scale, Multi-Institutional, Observational Study in China.

INTRODUCTION: To evaluate clinicopathologic features and prognosis of post-complete resection in patients with PDGFRA-mutant gastrointestinal stromal tumor (GIST), and even to establish a relapse-free survival (RFS) prognostic model for this subgroup. METHODS: This retrospective study used data from patients with primary PDGFRA-mutant GIST who underwent complete resection (2005-2019) at 16 large-scale medical centers in China. Stepwise multivariate Cox regression models were performed to build the prediction model, in which the potential predictors were available in routine clinical practice and using the risk score functions. The prediction model was cross-validated by calibration histogram and time-dependent receiver operating characteristic curves. RESULTS: A total of 280 patients with PDGFRA-mutant (172 D842V-mutant and 108 non-D842V-mutant) GIST after complete resection were enrolled. Most tumors originated in the stomach (89.6%). The 1-, 3-, and 5-year RFS rates were 95.9%, 91.2%, and 89.5%, respectively. The RFS of the non-D842V-mutant group was superior to that of the D842V group (P = 0.033). Multivariate analysis demonstrated that D842V mutation (P = 0.017), non-gastric tumor (P < 0.001), and Ki-67 > 5% (P = 0.005) were the independent variables influencing the prognosis of patients with PDGFRA-mutant GIST. The scoring model showed the predicted and actual cumulative 1-, 3- and 5-year follow-up relapse rates fit well. CONCLUSIONS: PDGFRA-mutant GIST mostly originated in the stomach and had a favorable prognosis after surgery. Non-D842V-mutant patients might have better prognoses than D842V-mutant patients. The prognostic model demonstrated favorable prediction accuracy, suggesting its clinical utility.

Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event.

BACKGROUND: Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST). It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. METHODS: Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. RESULTS: In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl), which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml). Three patients had higher levels (43.79~71.21 pg/ml) and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05) CONCLUSIONS: Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate.

Sonographically guided transthoracic biopsy of peripheral lung and mediastinal lesions: role of contrast-enhanced sonography.

OBJECTIVES: The purpose of this study was to assess the impact of contrast-enhanced sonography on sonographically guided transthoracic needle biopsy of lung lesions. METHODS: A total of 121 patients underwent sonographically guided transthoracic needle cutting biopsy. Of the 121 patients, 62 (contrast-enhanced sonography group) underwent contrast-enhanced sonography before biopsy, and the information from contrast-enhanced sonography was used to optimize the biopsy procedure. The remaining 59 patients constituted the non-contrast-enhanced sonography group. The enhancement patterns and echogenicity were evaluated by the consensus of 2 sonographers. The diagnostic efficacy was compared between the contrast-enhanced and non-contrast-enhanced sonography groups. RESULTS: The enhancement intensity and extent varied greatly among different thoracic lesions, and an anechoic area (necrosis) was revealed in 26 of 62 lesions (41.9%) lesions after administration of the contrast agent. The overall diagnostic accuracy of sonographically guided transthoracic biopsy in this study was 85.9% (104 of 121). In the contrast-enhanced sonography group, the initial biopsy led to correct diagnosis in 58 of 62 lesions (93.6%). In the non-contrast-enhanced sonography group, the initial biopsy led to correct diagnosis in 46 of 59 lesions (78.0%). The difference in the diagnostic accuracy between the contrast-enhanced and non-contrast-enhanced sonography groups was statistically significant (P < .05). CONCLUSIONS: Contrast-enhanced sonography enables differentiation of viable from necrotic portions of thoracic lesions and has a positive impact on the diagnostic efficacy of sonographically guided transthoracic needle biopsy.

Radiotherapy of unicentric mediastinal Castleman's disease.

Castleman's disease is a slowly progressive and rare lymphoproliferative disorder. Here, we report a 55-year-old woman with superior mediastinal Castleman's disease being misdiagnosed for a long term. We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms. The patient underwent an exploratory laparotomy, but the mass failed to be totally excised. Pathologic examination revealed a mediastinal mass of Castleman's disease. After radiotherapy of 30 Gy by 15 fractions, the patient no longer presented previous symptoms. At 3 months after radiotherapy of 60 Gy by 30 fractions, Computed tomography of the chest showed significantly smaller mass, indicating partial remission. Upon a 10-month follow-up, the patient was alive and free of symptoms.

[Meta-analysis of proximal gastrectomy and total gastrectomy for cancer of cardia and fundus].

OBJECTIVE: To assess the value of proximal gastrectomy (PG) and total gastrectomy (TG) for the treatment of cancer of cardia and fundus. METHODS: Publications on comparision between PG and TG in the treatment of cancer of cardia and fundus were collected, the data from the publications were matched with the PG group and the TG group respectively according to its corresponding surgical resection, and the data on postoperative complications, motality and 5-year survival rate were meta-analyzed by fixed effect model and random effect model. RESULTS: Thirteen reseaches on 2 219 patients were included in this study, 2 of which were randomly controlled studies. There were no significant differences in the postoperative complications (OR=1.00, 95%CI: 0.44-2.28,P>0.05) and mortality (OR=1.25, 95%CI: 0.62-2.48,P>0.05) between the PG group and the TG group, while there was significant difference in the 5-year survival rate (HR=0.87, 95%CI: 0.76-0.99,P=0.04). The 5-year survival rate in the TG group was higher than that in the PG group. CONCLUSION: Total gastrectomy for the treatment of cancer of cardia and fundus has better long-term therapetic effect.

Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.

ABSTRACT: Bevacizumab (BV) plus chemotherapy is broadly used in advanced ovarian cancer (OC). However, the efficacy of BV-based regimens for advanced OC patients is not satisfactory. Therefore, it is urgent to explore the predictive genetic biomarkers for BV.Tumor tissues from advanced OC patients receiving BV-based regimens were analyzed with a 150-gene targeted panel for next generation sequencing. The associations between gene alterations or clinicopathology features and progression-free survival (PFS) were analyzed by Kaplan-Meier curves or Cox regression. The association of the genetic alteration in potential predictive genes and expressions of 11 vascular endothelial growth factor-related genes were analyzed in The Cancer Genome Atlas cohort using 292 OC cases.Sixty two Chinese advanced OC patients treated with BV-based therapy were included. The median PFS of was 6.9 months, and objective response rate was 14.5%. In multivariate Cox regression analysis, the status of endothelial growth factor receptor (EGFR) (hazard ratio = 6.39, 95% confidence interval [CI] 2.25-18.13, P < .001) and human epidermal growth factor receptor 2 (HER2) (hazard ratio = 3.58, 95% CI 1.27-10.08, P = .016) were significantly correlated with PFS. MYC Proto-Oncogene amplification seemed to have a positive trend (hazard ratio = 0.21, 95% CI 0.05-1.02, P = .052). Moreover, EGFR and HER2 alterations were not prognostic factors of overall survival for OC in The Cancer Genome Atlas OC cohort. The vascular endothelial growth factor-related signature analysis indicated vascular endothelial factor A expression was upregulated with EGFR alterations (P = .034) which may be involved in BV resistance, and HER2 alterations were associated with hypoxia inducible factor 1 subunit alpha overexpression significantly (P = .029).EGFR or HER2 alterations are negative predictors of PFS for OC patient treated with BV plus chemotherapy. Therefore, the clinicians may consider to use alternative regimens such as anti-EGFR or anti-HER2 targeted therapy instead of BV-based regimens on these patients when standard care fail.

[Clinical significance of expressions of tumor markers in peripheral blood in non-small cell lung cancer].

OBJECTIVE: To investigate the expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in peripheral blood from the patients with non-small cell lung cancer and analyze their correlations with non-small cell lung cancer. METHODS: The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA were detected by nested reverse transcription-PCR assay in peripheral blood from the patients with non-small cell lung cancer (n = 120), benign pulmonary disease (n = 106) and from healthy subjects (n = 80) so as to further investigate their relationship with clinicopathological features and prognosis. Meantime we also examined the sensitivity, specificity and accuracy of combination detection. RESULTS: The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in non-small cell lung cancer patients were 56.7%, 57.5%, 35.0%, higher than that of benign pulmonary disease (0.9%, 6.6%, 5.7%) and healthy groups (0, 3.8%, 0, all P < 0.05). The ROC curves indicated the sensitivity of combined detection was 84.3% and the specificity of combined detection was 94.6%. Univariate analysis revealed that the clinical stage, the ECOG score and the number of positive marker had significant association with overall survival (OS) (χ(2) = 67.928, 95.981, 60.285, all P = 0.000). Multivariate analysis indicated that the clinical stage, ECOG score and the number of positive marker was an independent prognostic factor each (HR = 2.866, 4.251, 1.845, all P = 0.000). CONCLUSION: BJ-TSA-9, CK19 and Pre-proGRP mRNA may be the specific and sensitive markers to detect circulating tumor cells in the peripheral blood of non-small cell lung cancer patients.