SHP-1 promoter 2 methylation in cerebrospinal fluid for diagnosis of leptomeningeal epithelial-derived malignancy (carcinomatous meningitis)

Current diagnostic methods for leptomeningeal metastasis (LM) from epithelial-derived malignancy (EDM) have limited sensitivity. Here, we explored SHP-1 promoter 2 methylation (SHP1P2)—an epithelial-specific methylation marker previously proven as risk stratification and potential diagnostic marker in non-small cell lung cancer—for EDM with LM. We prospectively recruited 136 patients who were diagnosed EDM with LM (n?=?25), EDM without LM (n?=?14), non-EDM with LM (n?=?8), and benign meningeal diseases (n?=?89). The primary cancer sites for EDM with LM were lung (n?=?17), breast (n?=?5), and colon (n?=?3). We performed quantitative analyses of cell-free (cfSHP1P2) and whole fraction (wSHP1P2) from cerebrospinal fluid (CSF); results were correlated with the clinicopathological data, including CSF cytology. Median cfSHP1P2 and wSHP1P2 were 3.08 [range: 0–163.5] and 9.35 [0.69–91.63] ng/ml, respectively, in EDM with LM; 0 [0–0.08] and 0.23 [0–7.84] ng/ml in EDM without LM; and were undetectable in most cases of benign meningeal diseases and non-EDM with LM. The cut-off values of 0.22 ng/ml for methylated cfSHP1P2 and 0.59 ng/ml for wSHP1P2 were the best to discriminate EDM with LM from EDM without LM (sensitivity: 79–100?%; specificity: 83–100?%), as well as from other benign conditions (sensitivity: 85–100?% specificity: 78–100?%). CSF cytology yielded 76?% sensitivity for diagnosing EDM with LM. Further validation of CSF SHP1P2 methylation detection as a role of adjunctive tool for LM from EDM should be interested based on our study.     

The pre-operative predictive model for difficult elective laparoscopic cholecystectomy: A modification

BackgroundAlthough LC is a common operation, difficult cases are still challenging. Several studies have identified factors for the difficulty and conversion. Many scoring systems have been established for pre-operative prediction. This study aimed to investigate significant factors and validity of Randhawa’s model in our setting.MethodsThis prospective study enrolled LC patients in Hepato-Pancreato-Biliary Surgery unit between March 2018 and October 2019. The difficulty of operation was categorized into 3 groups by intra-operative grading scale. Multivariate analysis was performed to define significant factors of very-difficult and converted cases. The difficulty predicted by Randhawa’s model were compared with actual outcome. Area under ROC curve was calculated.ResultsAmong 152 patients, difficult and very-difficult groups were 59.2% and 15.1%, respectively. Sixteen cases needed conversion. Four factors (cholecystitis, ERCP, thickened wall, contracted gallbladder) for very-difficult group and 3 factors (obesity, biliary inflammation or procedure, contracted gallbladder) for conversion were significant. After some modification of Randhawa’s model, the modified scoring system provided better prediction in terms of higher correlation coefficient (0.41 vs 0.35) and higher AUROC curve (0.82 vs 0.75) than original model.DiscussionRandhawa’s model was feasible for pre-operative preparation. The modification of this model provided better prediction on difficult cases.     

The treatment landscape of advanced angiosarcoma in Asia—A multi-national collaboration from the Asian Sarcoma Consortium

Angiosarcoma (AS) is a rare disease with a dismal prognosis. The treatment landscape and prognostic factors for advanced AS, including locally advanced, unresectable, and metastatic disease remain elusive. The Asian Sarcoma Consortium is an international collaborative effort to understand the sarcoma treatment landscape in Asia. We undertook a retrospective chart review of AS patients seen in 8 sarcoma academic centers across Asia. Patients with complete clinical, treatment, and follow-up data were enrolled. Overall, 276 advanced AS patients were included into this study; 84 (30%) of the patients had metachronous metastatic AS. The median age was 67 y; primary sites of AS was cutaneous in 55% and visceral in 45% of patients. In total, 143 (52%) patients received at least 1 line of systemic chemotherapy. The most common first-line chemotherapy regimen used was paclitaxel (47.6%) followed by liposomal doxorubicin (19.6%). The median overall survival (OS) was 7.8 mo. Significant prognostic factors for OS included age > 65 (hazard ratio (HR) 1.54, P = .006), male gender (HR 1.39, P = .02), and a cutaneous primary AS site (HR 0.63, P = .004). The median progression-free survival (PFS) for first-line chemotherapy was 3.4 mo. PFS for single vs combination or paclitaxel vs liposomal doxorubicin chemotherapy regimens were comparable. This study provides an insight into the treatment patterns and prognostic factors of advanced AS patients in Asia. Prognosis of advanced AS remains poor. Data from this study serve as a benchmark for future clinical study design.