The Prognostic Value of Lymph Node Ratio after Neoadjuvant Chemotherapy in Patients with Locally Advanced Gastric Adenocarcinoma

Purpose@#This study aimed to investigate the prognostic value of lymph node ratio (LNR) in patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. @*Materials and Methods@#We retrospectively enrolled gastric cancer patients treated with neoadjuvant chemotherapy and curative surgery at the First Affiliated Hospital of Zhejiang University from 2004 to 2015 as the study cohort. Patients with the same inclusion criteria treated in 2016–2017 were enrolled as the validation cohort. Kaplan-Meier curves were assessed using the log-rank test to analyze the differences in overall survival (OS).Multivariate survival analysis was performed using the Cox proportional hazards model.The areas under the receiver operating characteristic curve of ypN and LNR categories for predicting the actual 3-year OS were compared. @*Results@#A total of 265 patients were included in the proposal cohort. The median number of retrieved lymph nodes (rLNs) was 32. The number of positive lymph nodes (pLNs) increased as rLN increased (P=0.037), but the LNR remained relatively constant (P=0.462). The LNR was categorized into 4 groups according to the prognosis: ypNr0, node-negative with rLN>25; ypNr1, node-negative with rLN≤25 or 00.3. In the validation cohort of 43 enrolled patients, there was a clear distinction in OS that significantly (P<0.001) varied depending on the LNR values and LNR was the only independent prognostic factor in multivariate analysis (P<0.001). @*Conclusions@#LNR was an independent prognostic factor for survival of patients with gastric cancer after preoperative chemotherapy and might be an alternative predictor for ypN stage.

Clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer / 中华消化外科杂志

Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 73 patients who underwent neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer at the First Affiliated Hospital of Zhejiang University between June 2004 and December 2009 were collected.Neoadjuvant chemotherapy regimens included XELOX and FOLFOX.Patients received radical gastrectomy within 2 weeks after the completion of the last cycle of neoadjuvant chemotherapy and then continued to undergo postoperative neoadjuvant chemotherapy.Observation indicators:(1) adverse event of neoadjuvant chemotherapy;(2) surgical and postoperative situations;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to December 2014.Measurement data with skewed distribution were described as M (range).Overall survival time was from the beginning of treatment to death or end of follow-up (patients with loss to follow-up).Progression-free survival time was from the beginning of treatment to tumor progression,recurrence and metastasis or death.The survival curve was drawn by the Kaplan-Meier method.Results (1) Adverse event of neoadjuvant chemotherapy:of 73 patients,38 received XELOX regimens and 35 received FOLFOX regimens,with a median cycle of 3 (range,1-7 cycles).There were 55 adverse events during neoadjuvant chemotherapy,including 47 with grade 1-2 and 8 with grade 3-4.(2) Surgical and postoperative situations:all the 73 patients underwent successful D2 radical gastrectomy for gastric cancer,including 40 receiving total gastrectomy,31 receiving distal gastrectomy,1 receiving total gastrectomy with transverse colon resection and 1 receiving distal gastrectomy with cholecystectomy.Of 73 patients,10 with postoperative complications were improved by conservative treatment,including 3 with pleural effusion,2 with peritoneal effusion,2 with anastomotic bleeding,2 with cholecystitis and 1 with lympha fistula.No patient received reoperations or died within 30 days postoperatively.Pathological TNM staging:22 patients were detected in stage Ⅰ-Ⅱ,45 in stage Ⅲ,4 in stage Ⅳ and 2 in stage T0N1M0.Three patients (in stage T0N0M0) had complete remission.Forty-three patients underwent postoperative chemotherapy.(3) Followup:all the 73 patients were followed up for 8-125 months,with a median time of 51 months.The median survival time,5-year overall survival rate and 5-year disease-free survival rate of 73 patients were 52 months,41.1％ and 34.2％,respectively.Conclusion XELOX and FOLFOX regimens of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer are safe and effective.

A Chinese multi-center study on the significance of monitoring imatinib plasma concentration in patients with gastrointestinal stromal tumor before and after administration / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.</p><p><b>METHODS</b>A cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.</p><p><b>RESULTS</b>Patients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).</p><p><b>CONCLUSIONS</b>The imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.</p>

Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report

Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation.

Clinical and laboratory diagnosis of adult hemophagocytic syndrome / 中国综合临床

Objective To investigate the clinical and laboratory diagnosis of adult hemophagocytic syn-drome (HPS) . Methods Clinical data of 24 patients with HPS from 2000 to 2008 were retrospectively analyzed. Results Of the 24 HPS cases, 12 had a malignant associated hemophagocytic syndrome (MHAS), and 10 were fi-nally diagnosed by bone marrow immunohistochemist ;Of 12 cases in non-MAHS group,4 were with virus associated hemophagocytic syndrome (VAHS), and 4 were of the other infections, whereas 4 patients diagnosed of immune associated HS (MAS). There were significant difference in onset age, mortality, serum lactate dehydrogenase (LDH) and serum ferritin(FER) and neutrophilic NAP between non-MAHS group and MAHS group(P <0.01 ,P<0.05). In all cases bone marrow biopsy showed significant differences in cytological and pathological features between MAHS group and non-MAHS group. Conclusion Etiology,immunology,and bone marrow cell biopsy and pathology as well contribute to the diagnosis and typing of HPS and will give a guide to the therapy.

The heterogeneous of large lymphocytic leukemia:6 cases report and clinical analysis / 中国基层医药

Objective To analyze and study the diagnosis of large granular lymphocyte leukemia(LGLL).Methods To report and discuss six cases weth LGLL we have found. Results 2 of T-LGLL and lof NK-LGLL had indolent process, mainly presenting with anemia and splenomegaly and good response to treatment, while; 1 of T-LGLL and 2 of NK-LGLL had aggressive process, their clinical characters are obviously general symptom, hepatomegaly,splenomegaly,these disease develop quickly and have bad prognosis. The immunophenotype of indolent LGLL is distinct from aggressive cases. Conclusion As a group of heterogeneous disease,its diagnosis should be based on clinical manifestation and immunophenotype and differentiated it carefully.

Acute Leukemia Patients with Complication of Infection:Their Clinical Features / 中华医院感染学杂志

OBJECTIVE To study the clinical features of acute leukemia(AL) patients with complication of infection. METHODS A retrospective analysis of prevalence of infection occurring in 123 AL patients,their bacterial spectrum,and the effect of G-CSF on the infection were done. RESULTS The prevalence of infection in AL patients was 94.3%,among which 49.2% were infected with Gram-positive organisms,42.4% with Gram-negative bacilli and 8.4% with fungi.Blood culture occurred mostly with Escherichia coli and Pseudomonas infection.Patient′s neutropenia was significantly related to the infection.The patients with neutrophil count less than 0.2?10~9/L had more frequently suffered severe infection with long-lasting time,and had more than two sites of infection.Age,hemoglobin level,prophylactic intestinal usage of antibiotics could not reduce patient′s infection.The total mortality of AL patients with infection was 6%.Pulmonary infection and septicemia increased mortality,but G-CSF therapy reduced it. CONCLUSIONS AL patients are at high risk of infection which is significantly associated with severe neutropenia.G-CSF therapy exerts an assistant role to antibiotics in controlling the infection.

Influence of HSP70 on combined method of hyperthermia and immunologic effector cells to treat cancer / 北京大学学报(医学版)

Objective: To investigate hyperthermia enhanced expression of heat shock protein70 (HSP70) in breast cancer drug sensitive cell line MCF7 and multi-drug resistant (MDR) cell line MCF7/ADR, so as to increase cytotoxic activity of immunologic effector cells against the target cells, and to provide an experimental basis for cell immunotherapy based on hyperthermia. Methods: The immunological effector cells were induced and expanded by cytokines. Breast cancer cell lines MCF7 and MCF7/ADR were treated at 42 ℃ for an hour. Then after being incubated for additional 4 hours, 24 hours and 48 hours, the cells were digested. Flow cytometry (FCM) was used to detect the expression of HSP70 on the target cells. MTT assay was employed to evaluate cell proliferation and the cytotoxic activity of immunologic effector cells against target cells. Results: The expressions of HSP70 in both the target cells had significant difference. The expression of HSP70 in MCF7/ADR cells was higher than in MCF7 cells before hyperthermia. After hyperthermia the expression of HSP70 increased by 6 folds in MCF7/ADR cells, and 22 folds in MCF7 cells and was higher than in MCF7/ADR cells at hour 4. The proliferation inhibition fraction of hyperthermia against MCF7 was significantly lower than that of MCF7/ADR. The cytotoxic activity of immunologic effector cells against MCF7 cells was lower than against MCF7/ADR cells before hyperthermia. After hyperthermia the cytotoxic activity of immunologic effector cells against MCF7 cells rose by 86.23%, and was higher than against MCF7/ADR cells (rose by 30.32%). Conclusion: The expression of HSP70 in breast cancer drug sensitive cell line MCF7 and MDR cell line MCF7/ADR were enhanced significantly by hyperthermia. Cytotoxic activity of immunologic effector cells against both the target cells were increased by hyperthermia. The differential expressions of HSP70 in breast cancer drug sensitive cell line MCF7 and MDR cell line MCF7/ADR affect the cytotoxic activity of immunologic effector cells.

Effective chemotherapy induce apoptosis in vivo in patients with leukemia / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate apoptosis in vivo in patients with leukemia at different stages of the first cycle of chemotherapy.</p><p><b>METHODS</b>We detected apoptosis of HL-60 cells and peripheral blood leukemia cells in 17 patients at different stages, using in situ terminal deoxynucleotidyl transferase (TdT) fluorescence measurement and DNA electrophoresis.</p><p><b>RESULTS</b>When HL-60 cells were incubated with 0.02 mg/L harringtonine for 0 to 48 hours, agarose gel electrophoresis showed that DNA ladder patterns became evident only at 12 hour into the treatment. In situ TdT assay showed that apoptotic cells occurred after one hour of the treatment. Apoptotic cells were few (0 - 3.3%) before chemotherapy, but increased substantially (11.4% - 87.5%) during chemotherapy in patients with complete remission (CR) or partial remission (PR). Apoptotic cells were few (0 - 6.1%) during chemotherapy in ten patients with no remission (NR). DNA ladder cannot be detected by agarose gel electrophoresis either before, during or after chemotherapy. Wilcoxon signed rank test shows: P = 0.0012 < 0.01, apoptotic cells during chemotherapy were present in greater quantity than prior to chemotherapy. Wilcoxon rank sum test shows: P = 0.0011 < 0.01, with the median of apoptotic cells during chemotherapy in patients with CR or PR more than with NR.</p><p><b>CONCLUSIONS</b>TdT assay can be used to detect apoptotic cells earlier and more sensitively than DNA agarose gel electrophoresis. In situ TdT assay is useful to detect apoptosis in vivo in the initial phase of chemotherapy for immediate modification of the chemotherapy regimen, whereas electrophoretic analysis is not sensitive enough to detect apoptotic cell in vivo. Where the median of apoptotic cells during chemotherapy in patients with CR or PR were greater than with NR, only effective drug therapy could induce apoptosis.</p>

Experimental study on TCRbeta idiotypic antigenic determinants DNA vaccine to induce anti-lymphoma antibodies / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the anti-human CEM lymphoma cell activities induced by TCR idiotypic DNA vaccine containing different antigen determinants in BALB/c mice.</p><p><b>METHODS</b>The specific rearranged gene fragment encoding TCRVbeta region of CEM cell line was obtained by RT-PCR technique. The PCR product was cloned into eukaryocytic expression vector pcDNA3, which was used as DNA vaccine and template for PCR amplifying different antigen determinant. Gene fragments encoding different antigen determinant were amplified and cloned into pcDNA3, separately. The experimental mice were immunized by intramuscular injection of the DNA vaccines. The specific anti-idiotype antibodies were detected by indirect immunofluorescence assay.</p><p><b>RESULTS</b>TCRbetaV of CEM cell line contains five antigen determinants. Specific anti-idiotype antibody was detected in all of the six mice immunized with DNA vaccine containing all the five determinants (the highest titer was 1:480). Although the antibody could also be detected in four of the six mice immunized with DNA vaccine containing four of the five antigen determinants, the antibody titer was lower (the highest titer was 1:80). DNA vaccine containing two of the five determinants could not induce the specific antibody.</p><p><b>CONCLUSION</b>The idiotypic DNA vaccine containing the whole TCRbetaV five antigen determinants could induce the specific anti-lymphoma idiotypic antibody in BALB/c mice.</p>

The Experimental Study on the TCR Idiotypic DNA Vaccine to Induce Antitumor Immune Response to Lymphocytic Malignancy / 中国实验血液学杂志

This study was undertaken to investigate the anti-lymphocytic malignacy immunologic effects induced by TCR idiotypic DNA vaccine on BALB/c mice. CEM lymphoma cell line and BALB/c mice were used as models. The rearrangement gene fragment coding TCR Vbeta region of CEM cell line was obtained by RT-PCR technique. The PCR product was cloned into the eukaryocytic expression vector pcDNA3 to be used as DNA vaccine. The experimental animals were immunized by intramuscular injection with DNA vaccine. The specific anti-idiotypic antibody was detected by indirect immunofluorescence assay. The specific anti-idiotypic cellular immunity was detected by CTL activity assay using MTT method. The results showed that specific anti-idiotypic antibody in the immunized mice sera could be found since four weeks after immunization and came to the peak of titer on the sixth week. Using IL-6 as immunological adjuvant could significantly increase the antibody titers. It was concluded that the TCR idiotypic DNA vaccine could induce effectively the specific anti-lymphoma idiotypic antibody in BALB/c mice. Using IL-6 as immunological adjuvant could significantly increase the antibody titers induced by idiotipic DNA vaccine.

The effects of FTY720 on lymphocytes and monocytes in mouse intestinal transplantation / 中国病理生理杂志

AIM: To test the effects of FTY720 on mouse intestinal allografts.METHODS: C_3H mice(H-2~k)were used as donor and C57BL/6 mice(H-2~b) as recipients.FTY720 group,allogeneic control group and isogeneic control group were set up.6 and 14 days after transplantation,murine intestinal grafts were harvested for histologic assessment.Lymphocytes were collected from mesenteric lymph nodes(MLN),Peyer's patch(PP),lamina propria lymphocytes(LPL) and intraepithelial lymphocytes(IEL) in the graft,then were analyzed by cytometry.RESULTS: Rejection was inhibited in FTY720 group at the 6th post-transplant day,although not at the 14th day.Recipient CD4~+ and CD8~+ T cells,CD19~+ B cells,as well as ?? TCR lymphocytes,were greatly reduced by FTY720 therapy.The similar action of FTY720 was also revealed in Gr1~+CD11b~+ monocytes.CONCLUSION: FTY720 is efficient on alleviating allo-immune response by reducing the infiltration of both lymphocytes and monocytes into the graft in a mouse intestinal transplantation model.

Ultimate cold preservation time in Ringer's solution for murine cardiac graft / 中国病理生理杂志

AIM: To determine the ultimate preservation time of murine cardiac grafts in 4℃ Ringer's solution. METHODS: Murine cardiac grafts were implanted to the abdominal vessels heterotopically 2, 4, 6, 8 and 10 hours after cold preservation. Graft survival rate and histological morphological changes, as well as the neutrilphil, T cell, macrophage infiltration, ICAM expression were determined by immunohistochemistry. RESULTS: The cardiac function-recovery rate and 1-week graft survival rate were 100% and 83.3% in 6-hour preservation group. Compared with non-preservation control group, no more apparent histological damages, cell infiltration and ICAM expression were found. CONCLUSION: The ultimate preservation time of murine cardiac graft in 4℃ Ringer's solution was 6 hours. [

In vitro perfusion method during cardiac graft preservation and its application in adenovirus mediated gene transfection / 中国病理生理杂志

AIM: To establish a method of in vitro donor heart perfusion in murine cardiac transplantation during preservation and apply it in adenovirus mediated gene transfection for donor heart. METHODS: Donor heart was transfected with recombinant adenovirus and stored for 2 hours after harvest, then it was transplanted heterotopically in abdomen. The grafts were appraisal by palpitation. Marked gene products were determined by X-Gal staining, aod T cell infiltration was determined by immunohistochemistry. The activation markers of recipients' lymphocytes were examed by cytometry. RESULTS: The grafts survival rate is 100% after perfusion and cold storage. The LacZ staining became strong 1 week after transplantation. The grafts remained an intact structure and no apparent T cell infiltration. The activation status of recipients' lymphocytes were not enhanced by transfected cardiac graft. CONCLUSION: In vitro perfusion during graft cold preservation is feasible for adenovirus mediated gene transfection. [

Clinical signipicance of mammaglobin detection in sentinel lymph nodes of breast cancer / 中国普通外科杂志

Objective To investigate the clinical significance of detecting mammaglobin in sentinel lymph nodes(SLN) of breast cancer. Methods In 32 breast cancer patients, methylene blue was injected around parechyma of breast cancer to locate the SLNs, and nested RT PCR(reverse transcriptase polgmecane chain reaction) was used to examine the expression of mammaglobin mRNA. Results The SLN was successfully identified in 30 of the 32 cases(93.8%).The micrometastases detection between group SLNs and non SLNs had significant statistical difference(P

The expression pattern of pleiotrophin in colorectal malignancy / 中国普通外科杂志

ObjectiveTo study the expression of pleiotrophin (PTN) in colorectal cancer and its impact on the malignancy.MethodsRT PCR and immunoperoxidase staining were applied on the resected samples.ResultsPTN mRNA was expressed in 18 cases of 24 colorectal cancer tissues and 18 cases of 19 adjacent normal tissues. PTN protein was also found expressed in stroma, but the expression rate was higher in colorectal cancer tissues (34%) than in adjacent normal tissues (9%, P