Advanced gastric cancer, characterized by high heterogeneity and poor prognosis, has traditionally been managed with a palliative care-centric comprehensive treatment. The concept of conversion therapy aims to reduce tumor staging and achieve complete tumor resection after comprehensive treatment of initially unresectable tumors, thereby improving patient prognosis. Recent large-scale clinical studies have demonstrated that immune checkpoint inhibitors combined with chemotherapy can significantly increase the objective remission rate and improve the survival of patients with advanced gastric cancer. Meanwhile, with the extensive development of multidisci-plinary teams and the advancement of surgical techniques, conversion therapy has shown great potential in improving the prognosis of advanced gastric cancer. However, due to the complexity of advanced gastric cancer in terms of local staging, metastatic sites, and molecular typing, there are still many controversies and unanswered questions in the field of conversion therapy. The authors systematically elaborate on the research progress of gastric cancer conversion therapy both domes-tically and internationally, and explore the current status and clinical issues of conversion therapy for advanced gastric cancer.

Objective: To analyze the clinical characteristics, treatment and prognosis of primary gastric lymphomas (PGL). Methods: A retrospective study was conducted in 124 cases of PGL from July 2009 to January 2016 in our hospital, and the clinical records, pathological and immunohistochemical features were analyzed. The relationship between different factors at diagnosis and prognosis were studied. Results: 124 cases of PGL included 93 diffuse large B cell lymphoma (DLBCL) patients, 25 mucosa associated lymphoid tissue (MALT) lymphoma cases, 1 mantle cell lymphoma, 4 peripheral T-cell lymphoma-not otherwise specified, and 1 extra-nodal NK/T-cell lymphoma-nasal type. Of the 93 primary gastric DLBCL (PG-DLBCL) patients, the germinal center B cell-like (GCB) DLBCL were 45 cases, non-GCB DLBCL were 48 cases. 10 cases (10.8%) of 93 PG-DLBCL were transformed from gastric MALT, and 7 cases (7.5%) have bone marrow involvement. Evidence of Helicobacter pylori infection was detected in 21 cases (51.2%) of 41 DLBCL patients and in 10 cases (43.5%) of 23 MALT patients. Univariate analysis revealed that clinical stages (P=0.002) , B symptoms (P=0.001) , international prognostic index (IPI) score (P<0.001) , anemia (P<0.001) , low level of serum albumin level (P=0.001) , high level of lactate dehydrogenase (LDH) (P<0.001) , high β2-microglobulin (P=0.003) , chemotherapy uncombined with rituximab (P=0.006) were factors affecting progression-free survival (PFS). Multivariate Cox regression analysis indicated that clinical stages (HR=5.113, 95% CI 1.087-24.048, P=0.039) and LDH (HR=5.111, 95%CI 1.651-15.827, P=0.005) were independent poor prognosis factors affecting PFS. In the non-GCB group, the PFS was significantly extended (P=0.013) , the OS has no statistical significance (P=0.764). The PFS was significantly shortened in MALT transformed to DLBCL compared with MALT lymphoma patients (P=0.016) , but have no statistical significance compared with DLBCL patients (P=0.373). Conclusions The types of DLBCL and MALT are more common in PGL. PG-DLBCL is a highly heterogeneous malignant tumor, and advanced clinical stages and high LDH value are associated with poor outcome.

Objective: To evaluate the prognostic value of lymphocyte-to-monocyte ratio (LMR) in angioimmunoblastic T cell lymphoma (AITL). Methods: Data of 64 patients diagnosed as AITL at the First Affiliated Hospital of Nanjing Medical University between June 2009 and July 2017, were analyzed retrospectively. Receiver Operator Characteristic (ROC) curve was used to calculate the cutoff value of LMR to divide this cohort of patients into high and low LMR groups. Characteristics between groups were compared by Pearson Chi-square or Fisher exact tests. Kaplan-Meier method and Cox regression were performed to probe prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Results: A total of 64 cases [39 cases male and 25 ones female with the median age of 63 (29-89) years old] were enrolled. The cutoff value of LMR was 3.07. Patients with low LMR showed inferior PFS (9 months vs 13 months, P=0.044) and OS (16 months vs not reached, P=0.014), respectively than those without low LMR during a median follow-up of 33 months (5 to 103 months). Multivariate analysis showed that low LMR was an independent prognostic factor associated with poor outcomes (HR=0.48, 95% CI 0.26-0.92 for PFS, P=0.027; HR=0.38, 95% CI 0.18-0.82 for OS, P=0.013, respectively). Subgroup analysis showed that patients with low LMR and under the situation of high score of Prognostic Index for peripheral T-cell lymphoma, Unspecified (PIT) (2-4) had shorter PFS and OS (P=0.013 and P=0.031, respectively). But in low score of PIT (0-1) group, low LMR seemed to play almost no effects on PFS and OS (P=0.949 and P=0.238, respectively). Conclusions The disease risk status of patients could be initially assessed according to PIT score and LMR level. Low LMR was demonstrated to be able to predict poor outcome in AITL.

OBJECTIVE: To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM). METHODS: Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored. RESULTS: The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants. CONCLUSION The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.
Humans ; Immunoglobulin Heavy Chains/genetics* ; Multigene Family ; Mutation ; Waldenstrom Macroglobulinemia/genetics*

Objective: To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients. Methods: Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system. Results: ①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old. The median treatment-free survival (TFS) and overall survival (OS) was 16 months (4-24 months) and 180 months (145-215 months), respectively. ② The median TFS for low (n=60), intermediate (n=50), high (n=45) and very high risk group (n=60) according to the CLL-IPI scoring system was 56, 15, 12 and 5 months, respectively (P<0.001). ③ The median follow-up was 48 months (1-192 months). The median OS for low risk group was not reached and for intermediate, high, and very high risk group was 180, 89 and 74 months, respectively. The estimated 5-year OS rate was 97.6%, 83.7%, 67.8% and 55.2%, respectively (P<0.001). ④ Multivariate analysis indicated that unmutated immunoglobulin heavy chain variable region (IGHV) gene and β₂-microglobulin>3.5 mg/L(P<0.001) were independent prognostic factors of TFS, while TP53 deletion and/or mutation(P=0.008), unmutated IGHV (P=0.017) and age>65 years(P=0.045) were independent prognostic factors of OS. Conclusion CLL-IPI is the powerful tool for risk stratification in Chinese CLL patients.

Objective: To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT. Methods: The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β₂-microglobulin (β₂-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed. Results: Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β₂-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn’t receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences. Conclusion CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Objective: To reveal clinical features, pathological diagnosis, treatment and prognosis of primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma and review literatures. Methods: The clinical characteristics, pathological diagnosis, laboratory texts, treatment and prognosis of 7 cases of primary thymic MALT lymphoma identified at the First Affiliated Hospital of Nanjing Medical University from November 2017 to January 2019 were collected and analyzed. Results: Of 7 primary thymic MALT lymphoma cases, six were female. Patients were often asymptomatic and were found mediastinal mass by chest CT. After mediastinal mass resection, pathologist reported a primary thymic MALT lymphoma. Laboratory tests showed all patients were positive for anti-nuclear antibody, anti-Ro52 antibodies and anti-Sjogren’s syndrome A antibodies, and increased erythrocyte sedimentation rate (ESR) . Four were diagnosed with Sjogren’s syndrome (SS) . After surgery, the patients were given the positron emission tomography computed tomography (PET-CT) scans. All cases received "watch and wait" approach. Up to now, all cases showed good prognoses and none of them relapsed. Conclusion Primary thymic MALT lymphoma was rare, and it was often associated with autoimmune diseases. Such patients who usually had good prognoses should be followed up closely and avoided excessive treatments if there were no indications of intervention.

Objective: To evaluate the prognostic value of lymphocyte to monocyte ratio (LMR) and PET scan performed after first two cycles of chemotherapy (PET-2) in Hodgkin’s lymphoma (HL) . Methods: The clinical data of 133 patients with HL diagnosed from January 2007 to March 2016 at the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The X-tile software was used to calculate the optimal cut-off value of LMR. Kaplan-Meier method and Cox regression were used for survival analysis. Results: The median age of 133 HL patients was 33 (18–84) years, and the male to female ratio was 1.9∶1. The optimal cut-off value of LMR was 2.5, and progression free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001) were significantly lower in the LMR<2.5 group than that of LMR≥2.5. Multivariate survival analysis showed that LMR<2.5 was an independent predictor of PFS (P=0.002, HR=2.35, 95%CI 1.36–4.07) and OS (P=0.002, HR=10.36, 95%CI 2.35–45.66) in HL patients. The analysis of PET-2 from 56 HL patients showed that PET-2 positive patients had significantly poorer PFS (P=0.022) . After grouping LMR combined with PET-2, significant differences were found in PFS and OS between the three groups (P values were 0.009 and 0.012) . Conclusion LMR<2.5 is an independent prognostic factor for patients with HL. PET-2 combined with LMR may have better prognostic value.