Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the most common gastrointestinal lymphoma. The prognostic/predictive indicators among patients with gastric and intestinal DLBCL (giDLBCL) are controversial beyond their anatomical sites. We compared giDLBCL cases and investigated the clinical utility of newly emerging indicators with an emphasis on programmed cell death ligand 1 (PD-L1) expression. This retrospective study included 174 patients with primary gastric (n = 129) or intestinal (n = 45) DLBCL treated with rituximab-containing chemotherapy between 1995 and 2018. Compared with gastric DLBCL (gDLBCL) cases, patients with intestinal DLBCL (iDLBCL) had a significantly higher rate of advanced Lugano stage (71% vs 37%, P < 0.001), perforation (13% vs. 0.8%, P = 0.001), PD-L1 expression on microenvironment immune cells (miPD-L1, 70% vs 46%, P = 0.008), CD10 positivity (47% vs 28%, P = 0.027), and CD5 positivity (9% vs 1.6%, P = 0.040). The iDLBCL patients showed significantly worse progression-free survival (PFS) and overall survival (OS) than gDLBCL cases (P = 0.0338 and P = 0.0077, respectively). PD-L1 expression on tumor cells was detected in only 3 (2%) of 174 cases with early relapse and/or an aggressive clinical course; whereas, miPD-L1-positive cases had significantly better OS than the miPD-L1-negative gDLBCL and iDLBCL cases (P = 0.0281 and P = 0.0061, respectively). Multivariate analysis revealed that miPD-L1 negativity (P = 0.030) was an independent adverse prognostic factor for OS in giDLBCL. The anatomical site of disease did not influence outcome in giDLBCL cases treated with rituximab-containing chemotherapy; while, miPD-L1 expression had a favorable impact on the outcome.

Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma

EZH2 overexpression in primary gastrointestinal diffuse large B-cell lymphoma and its association with the clinicopathological features

Objective In the present study, we aimed to evaluate the prognostic value of PET/CT-derived radiomic features for patients with B-cell lymphoma (BCL), who were treated with CD19/CD22 dual-targeted chimeric antigen receptor (CAR) T cells. Moreover, we explored the relationship between baseline radiomic features and the occurrence probability of cytokine release syndrome (CRS). Methods A total of 24 BCL patients who received 18F-FDG PET/CT before CAR T-cell infusion were enrolled in the present study. Radiomic features from PET and CT images were extracted using LIFEx software, and the least absolute shrinkage and selection operator (LASSO) regression was used to select the most useful predictive features of progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curves, Cox proportional hazards model, and Kaplan-Meier curves were conducted to assess the potential prognostic value. Results Contrast extracted from neighbourhood grey-level different matrix (NGLDM) was an independent predictor of PFS (HR = 15.16, p = 0.023). MYC and BCL2 double-expressor (DE) was of prognostic significance for PFS (HR = 7.02, p = 0.047) and OS (HR = 10.37, p = 0.041). The combination of NGLDM_ContrastPET and DE yielded three risk groups with zero (n = 7), one (n = 11), or two (n = 6) factors (p < 0.0001 and p = 0.0004, for PFS and OS), respectively. The PFS was 85.7%, 63.6%, and 0%, respectively, and the OS was 100%, 90.9%, and 16.7%, respectively. Moreover, there was no significant association between PET/CT variables and CRS. Conclusions In conclusion, radiomic features extracted from baseline 18F-FDG PET/CT images in combination with genomic factors could predict the survival outcomes of BCL patients receiving CAR T-cell therapy.

/pdf/prognostic-value-of-radiomic-features-of-18f-fdg-pet-ct-in-bc25wmmo.pdf

Prognostic Value of Radiomic Features of 18F-FDG PET/CT in Patients With B-Cell Lymphoma Treated With CD19/CD22 Dual-Targeted Chimeric Antigen Receptor T Cells

PURPOSE: To evaluate whether the addition of two biological markers (MYC and BCL-2 protein overexpression) improves the stratification of high-risk patients with diffuse large B-cell lymphoma (DLBCL).

METHOD: Seven risk factors were identified at diagnosis, and a maximum of 7 points were assigned to each patient. The patients were classified according to four risk groups: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Only high-risk patients with DLBCL were included in this analysis. We retrospectively examined 20 cases from 2008 to 2013 at the Nanjing Drum Tower Hospital.

RESULTS: The median expression of MYC protein was 60%, and 17 of 20 (65%) evaluable cases overexpressed MYC. The median expression of BCL-2 protein was also 60%. Eighteen of 20 (90%) evaluable cases showed BCL-2 overexpression. Additionally, 12 out of 20 cases (60%) demonstrated coexpression of MYC and BCL-2 proteins. The percentages of overall survival and progression-free survival at the median follow-up time (36 months) were 33.3%±16.1% and 16.9%±13.5%, respectively. By comparison, nine, four, and 20 patients were classified as high risk based on the International Prognostic Index (IPI), National Comprehensive Cancer Network(NCCN)-IPI, and revised IPI criteria, respectively. According to the IPI and NCCN-IPI stratification, the risk groups demonstrated closely overlapping survival curves. In addition, four out of 20 cases were identified as low-intermediate risk according to the NCCN-IPI criteria.

CONCLUSION: The addition of MYC and BCL-2 protein expression to the IPI could identify a subset of DLBCL patients with high-risk clinicopathological characteristics and poor clinical outcome.

/pdf/combination-of-bcl-2-and-myc-protein-expression-improves-5gjcify3yn.pdf

Combination of BCL-2 and MYC protein expression improves high-risk stratification in diffuse large B-cell lymphoma.

Endoscopic nasobiliary drainage (ENBD) was often used for preoperative biliary drainage in cases like cholangiocarcinoma or acute obstructive suppurative cholangitis, reports on endoscopic nasobiliary drainage (ENBD) over primary closure of the common bile duct (CBD) are limited. This study compares outcomes of laparoscopic cholecystectomy (LC) + laparoscopic CBD exploration (LCBDE) + intraoperative ENBD + primary closure of CBD with equivalent patients who underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP) and subsequent LC. From January 2013 to December 2015, 829 consecutive patients with choledocholithiasis combined with cholecystolithiasis underwent surgery in our department. 211 patients underwent LC + LCBDE + intraoperative ENBD + primary closure of CBD (group A) and 117 preoperative ERCP + subsequent LC (group B). A total of 501 patients (355 who underwent T-tube drainage and 146 who underwent transcystic exploration) were excluded from the analysis. Clinical records, operative findings, and postoperative follow-up were analyzed. Age and sex distribution, comorbidity, presentations, CBD diameter, and size and number of stones were similar in the two groups, and there was no postoperative mortality. Duration of surgery in group A was shorter (83 vs. 104 min, P < 0.01), as was postoperative hospital stay (6 vs. 9 days, P < 0.01). Average operative expenditure in group A was less than that of group B ($ 3816 vs. $ 4015, P < 0.01). The success rate in group A was higher (100 vs. 91%, P < 0.01). Ten patients in group B converted to LCBDE. The postoperative complication rate was higher in group B but without significant difference (1.9 vs. 4.2%, P = 0.29). Median follow-up time was 24 (3–28) months (n = 302 patients). Two patients in group B reported residual stones. LC + LCBDE + intraoperative ENBD + primary closure of CBD should have priority over preoperative ERCP + subsequent LC for choledocholithiasis combined with cholecystolithiasis.

Intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for choledocholithiasis combined with cholecystolithiasis: a cohort study of 211 cases.

AIM: To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) patients, and explore its associations with patients’ clinical parameters.

METHODS: Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained, and 30 lymphoid tissue samples from reactive lymph nodes of age- and sex-matched patients represented control samples. Staging and diagnostic procedures were conducted according to the Lugano staging system. All patients had been treated with three therapeutic modalities: surgery, chemotherapy, or radiotherapy. Expression of MYC and BCL-2 were detected at both protein and mRNA levels by immunohistochemistry and real-time RT-PCR.

RESULTS: Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 mRNA expression, respectively (both P < 0.05). We found that advanced-stage disease (at IIE-IV) was associated with MYC and BCL-2 coexpression levels (P < 0.05). In addition, MYC+/BCL-2+ patients had more difficulty in achieving complete remission than others (P < 0.05). Presence of MYC protein expression only affected overall survival and progression-free survival (PFS) when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (P < 0.05) even after adjusting for age, Lugano stage, international prognostic index, and BCL-2 protein expression in a multivariable model.

CONCLUSION: MYC+/BCL-2+ patients have worse chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting clinical outcomes of PGI-DLBCL patients.

Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma

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Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma