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.

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 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 current status of surgical intervention after conversion therapy for advanced gastric cancer.Methods:The retrospective cross-sectional investigation study was conducted. The investigation was conducted on clinicians who were qualified for the diagnosis and treatment of gastric cancer in 161 hospitals nationwide from December 11 to 22,2023. The questionnaire of "Survey on the Current Status of Surgical Intervention after Conversion Therapy for Advanced Gastric Cancer" was designed and distributed through WeChat based on the software platform of Wenjuanxing. Count data were expressed as absolute numbers and percentages.Results:(1) Results of the questionnaire. Of the 233 clinicians, the percentage of completed questionnaires, recovered questionnaires, and valid questionnaires were all of 100.00%(233/233). (2) Basic information of clinicians. Of the 233 clinicians, there were 213 males and 20 females. The numbers of clinicians aged ≤30 years, 31-40 years, 41-50 years, and >50 years were 1, 47, 109, and 76, respectively. The numbers of surgeons, internists, radiotherapists, and pathologists were 193, 36, 3, and 1, respectively. The numbers of chief physicians, deputy chief physicians, attending physicians, and resident physicians were 133, 75, 21, and 4, respectively. The numbers of clinicians with years of practice as >20 years, 11-20 years, 6-10 years, and ≤5 years were125, 88, 19, and 1, respectively. The numbers of clinicians from provincial-level tertiary general hospitals, provincial-level tertiary specialized oncology hospitals, municipal-level tertiary hospitals, and tertiary hospitals of B and below were 102, 58, 59, and 14, respectively. (3) Conversion therapy of advanced gastric cancer. Of the 233 clinicians, there were 54.94%(128/233) of clinicians whose units had admitted more than 100 gastric cases per year, 81.97%(191/233) of clinicians whose units had experience in surgical resection after conversion therapy of advanced gastric cancer, 66.52%(155/233) of clinicians whose units had proportion of successful surgical resection after conversion therapy of advanced gastric cancer exceeded 5%, and 51.50%(120/233) of clinicians whose units had the proportion of laparoscopic exploration+peritoneal lavage cytology to clarify the tumor stage at the initial diagnosis ≤10%. (4) Strategy selection after conversion therapy for advanced gastric cancer. Of the 233 clinicians, 63.52%(148/233) of them routinely mentioned to patients that they might be able to obtain chance of surgery after conversion therapy. There were 85.41%(199/233), 79.83%(186/233), and 68.67%(160/233) of clinicians considering possible risks as drug resistance, subsequent chemotherapy-immunotherapy or radiotherapy and other related adverse reactions and aggravation of distant toxicity, and distant organ metastasis for advanced gastric cancer patients to continue palliative care after conversion therapy. There were 85.41%(199/233), 50.21%(117/233), and 18.45%(43/233) of clinicians considering choices as multi-disciplinary treatment to evaluate the follow-up treatment strategy, laparoscopic exploration to clarify the possibility of surgery, and continuing the original program of palliative care for follow-up treatment of patients with advanced gastric cancer after conversion therapy. There were 97.85%(228/233) of clinicians considering re-evaluating the possibility of surgical resection when the tumor volume was significantly reduced after conversion therapy. (5) Selection of beneficiary population, treatment modality, and time point of evaluation of benefit for patients undergoing conversion surgery for advanced gastric cancer. A further questionnaire survey was conducted on the 228 clinicians who chose "to consider re-evaluating surgical resection when the volume of tumor reducted significantly after conversion therapy for advanced gastric cancer". There were 94.74%(216/228) of clinicians considering advanced gastric cancer patients with high expression of programmed death receptor ligand 1 as beneficiary population of conversion therapy. There were 82.46%(188/228) of clinicians considering advanced gastric cancer patients with liver oligometastases as beneficiary population of conversion therapy. There were 53.07%(121/228) of clinicians considering two-drug chemotherapy+immunotherapy regimen as preferred for HER2-negative patients, there were 67.54%(154/228) of clinicians considering chemotherapy + trastuzumab + immunotherapy regimen as preferred for HER2-positive patients. There were 83.33%(190/228) of clinicians considering resection treatment after 3-6 cycles of conversion therapy. There were 94.74%(216/228) of clinicians choosing enhanced computed tomography scan to evaluate the efficacy. In terms of tumor sign for laparoscopic surgery after conversion therapy, there were 92.54%(211/228) of clinicians choosing significant shrinkage of the primary focus and its surrounding lymph nodes from baseline. There were 63.16%(144/228) of clinicians choosing surgery after 3-4 weeks of drug withdrawal, and 57.02%(130/228) of clinicians considering to achieve R 0 resection. In terms of patients achieving pathologic complete remission (pCR) after surgery, there were 64.04%(146/228) of clinicians believing that postoperative treatment should be continued for 6-8 cycles of therapy followed by maintenance therapy up to 1 year. For patients with non-pCR, there were 59.65%(136/228) of clinicians believing that 6-8 cycles of postoperative maintenance therapy should be continued until 1 year. Conclusion:Most clinicians in China consider R 0 resection after conversion therapy for patients with advanced gastric cancer, followed by 6-8 cycles of treatment and maintenance therapy for another year.

Objective:To investigate the current status of surgical intervention after conversion therapy for advanced gastric cancer.Methods:The retrospective cross-sectional investigation study was conducted. The investigation was conducted on clinicians who were qualified for the diagnosis and treatment of gastric cancer in 161 hospitals nationwide from December 11 to 22,2023. The questionnaire of "Survey on the Current Status of Surgical Intervention after Conversion Therapy for Advanced Gastric Cancer" was designed and distributed through WeChat based on the software platform of Wenjuanxing. Count data were expressed as absolute numbers and percentages.Results:(1) Results of the questionnaire. Of the 233 clinicians, the percentage of completed questionnaires, recovered questionnaires, and valid questionnaires were all of 100.00%(233/233). (2) Basic information of clinicians. Of the 233 clinicians, there were 213 males and 20 females. The numbers of clinicians aged ≤30 years, 31-40 years, 41-50 years, and >50 years were 1, 47, 109, and 76, respectively. The numbers of surgeons, internists, radiotherapists, and pathologists were 193, 36, 3, and 1, respectively. The numbers of chief physicians, deputy chief physicians, attending physicians, and resident physicians were 133, 75, 21, and 4, respectively. The numbers of clinicians with years of practice as >20 years, 11-20 years, 6-10 years, and ≤5 years were125, 88, 19, and 1, respectively. The numbers of clinicians from provincial-level tertiary general hospitals, provincial-level tertiary specialized oncology hospitals, municipal-level tertiary hospitals, and tertiary hospitals of B and below were 102, 58, 59, and 14, respectively. (3) Conversion therapy of advanced gastric cancer. Of the 233 clinicians, there were 54.94%(128/233) of clinicians whose units had admitted more than 100 gastric cases per year, 81.97%(191/233) of clinicians whose units had experience in surgical resection after conversion therapy of advanced gastric cancer, 66.52%(155/233) of clinicians whose units had proportion of successful surgical resection after conversion therapy of advanced gastric cancer exceeded 5%, and 51.50%(120/233) of clinicians whose units had the proportion of laparoscopic exploration+peritoneal lavage cytology to clarify the tumor stage at the initial diagnosis ≤10%. (4) Strategy selection after conversion therapy for advanced gastric cancer. Of the 233 clinicians, 63.52%(148/233) of them routinely mentioned to patients that they might be able to obtain chance of surgery after conversion therapy. There were 85.41%(199/233), 79.83%(186/233), and 68.67%(160/233) of clinicians considering possible risks as drug resistance, subsequent chemotherapy-immunotherapy or radiotherapy and other related adverse reactions and aggravation of distant toxicity, and distant organ metastasis for advanced gastric cancer patients to continue palliative care after conversion therapy. There were 85.41%(199/233), 50.21%(117/233), and 18.45%(43/233) of clinicians considering choices as multi-disciplinary treatment to evaluate the follow-up treatment strategy, laparoscopic exploration to clarify the possibility of surgery, and continuing the original program of palliative care for follow-up treatment of patients with advanced gastric cancer after conversion therapy. There were 97.85%(228/233) of clinicians considering re-evaluating the possibility of surgical resection when the tumor volume was significantly reduced after conversion therapy. (5) Selection of beneficiary population, treatment modality, and time point of evaluation of benefit for patients undergoing conversion surgery for advanced gastric cancer. A further questionnaire survey was conducted on the 228 clinicians who chose "to consider re-evaluating surgical resection when the volume of tumor reducted significantly after conversion therapy for advanced gastric cancer". There were 94.74%(216/228) of clinicians considering advanced gastric cancer patients with high expression of programmed death receptor ligand 1 as beneficiary population of conversion therapy. There were 82.46%(188/228) of clinicians considering advanced gastric cancer patients with liver oligometastases as beneficiary population of conversion therapy. There were 53.07%(121/228) of clinicians considering two-drug chemotherapy+immunotherapy regimen as preferred for HER2-negative patients, there were 67.54%(154/228) of clinicians considering chemotherapy + trastuzumab + immunotherapy regimen as preferred for HER2-positive patients. There were 83.33%(190/228) of clinicians considering resection treatment after 3-6 cycles of conversion therapy. There were 94.74%(216/228) of clinicians choosing enhanced computed tomography scan to evaluate the efficacy. In terms of tumor sign for laparoscopic surgery after conversion therapy, there were 92.54%(211/228) of clinicians choosing significant shrinkage of the primary focus and its surrounding lymph nodes from baseline. There were 63.16%(144/228) of clinicians choosing surgery after 3-4 weeks of drug withdrawal, and 57.02%(130/228) of clinicians considering to achieve R 0 resection. In terms of patients achieving pathologic complete remission (pCR) after surgery, there were 64.04%(146/228) of clinicians believing that postoperative treatment should be continued for 6-8 cycles of therapy followed by maintenance therapy up to 1 year. For patients with non-pCR, there were 59.65%(136/228) of clinicians believing that 6-8 cycles of postoperative maintenance therapy should be continued until 1 year. Conclusion:Most clinicians in China consider R 0 resection after conversion therapy for patients with advanced gastric cancer, followed by 6-8 cycles of treatment and maintenance therapy for another year.

Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Lymphoma, Non-Hodgkin/drug therapy* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols

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 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.

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.