Treatment and prognosis of patients of G3 nonfunctional pancreatic neuroendocrine tumors with proliferation index of Ki-67<55% / 中华消化外科杂志

Objective:To investigate the treatment and prognosis of patients of G3 non-functional pancreatic neuroendocrine tumors (pNETs) with proliferation index of Ki-67 <55%.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 G3 non-functional pNETs patients with proliferation index of Ki-67<55% who were admitted to Zhongshan Hospital of Fudan University from April 2014 to April 2020 were collected. There were 11 males and 4 females, aged (58±10)years. All patients underwent radical resection of the primary lesion. Obser-vation indicators: (1) treatment; (2) postoperative pathological characteristics; (3) follow-up. Measure-ment data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. The Pearson correlation analysis was used to verify the correlation between variables. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Log-Rank test was used for survival analysis. Results:(1) Treatment. All 15 G3 nonfunctional pNETs patients underwent radical resection of the primary lesion of pancreas, including 5 cases receiving pancreati-coduodenectomy, 10 cases receiving distal pancreatectomy with splenectomy. There were 5 patients with simultaneous liver oligometastasis who underwent combined segmental (lobectomy) hepatectomy. All 15 patients had negative tumor margin, and the operation time and volume of intraoperative blood loss of 15 patients was 120(90,210)minutes and 200(50,300)mL, respectively. None of patient had complications ≥Ⅲ grade of the Clavien-Dindo classification during the postoperative 30 days. Of the 15 patients, there were 5 cases receiving comprehensive treatment based on CAPTEM chemo-therapy (temozolomide combined with capecitabine), 2 cases receiving local interventional therapy, 2 cases receiving CAPTEM chemotherapy, 1 case receiving local interventional therapy combined with molecular targeted therapy, 1 case receiving local interventional therapy combined with long acting somatostatin therapy, 1 cases receiving long acting somatostatin therapy combined with molecular targeted therapy, and 3 cases without postoperative treatment. (2) Postoperative patholo-gical characteristics. The tumor diameter of 15 patients was 3.3(range, 0.5-6.0)cm. There were 2 cases with tumor diameter <2 cm, 13 cases with tumor diameter ≥2 cm. The number of lymph nodes dissected and number of lymph nodes metastatic was 6(4, 10) and 2(1,3) in 15 patients, respectively, including 12 cases with positive lymph node metastasis. Of the 15 patients, there were 5 cases with tumor invasion of adjacent organ, 5 cases with simultaneous liver metastasis, 8 cases with perineural invasion and 8 cases with vascular invasion. There were 3, 7, and 5 patients with stage Ⅱ, stage Ⅲ, and stage Ⅳ of pathological TNM staging, respectively. The proliferation index of Ki-67 and mitotic count was 32%±9% and (11±9)/10 high power field in the primary lesion of 15 patients, respectively, and there was no correlation between proliferation index of Ki-67 and mitotic count ( P>0.05). (3) Follow-up. All 15 patients were followed up after surgery for (55±24)months. The median survival time of 15 patients was 78(range, 43-113)months, with 1-, 3-, 5-year overall survival rate as 100%, 92%, 62%, respectively. During the follow up, 9 of the 15 patients underwent tumor recurrence, with the recurrence time as 20(14, 44)months. There were 8 patients died of tumor recurrence or metastasis. The median survival time was 86(range, 51-120)months in 5 patients receiving comprehensive treatment based on CAPTEM chemotherapy, versus 53(range, 45-60)months in 10 patients receiving other postoperative adjuvant therapy or without postoperative treatment, showing a significant difference between them ( χ2=4.21, P<0.05). Conclusion:The prognosis of patients of G3 nonfunctional pNETs with proliferation index of Ki-67<55% undergoing radical resection combined with postoperative comprehensive treatment based on CAPTEM chemotherapy in better than that of patients receiving other postoperative adjuvant therapy or without posto-perative treatment.

Invasion of tumor associated macrophages and its influence on the prognosis in cardia carcinoma / 肿瘤研究与临床

Objective:To explore the association of tumor associated macrophages (TAM) with tumor invasiveness, metastasis and prognosis in cardia carcinoma tissues.Methods:The cancer tissues and pericarcinomatous tissues of 100 patients with cardia carcinoma who underwent D2 radical operation in the First Hospital of Putian City from January 2014 to January 2015 were collected. M2-type TAM was marked with CD163. The tissue microarray was made and the expression of CD163 in microarray tissues was detected by using immunohistochemistry. The median number of CD163 positive cells in all cancer tissues was taken as the cut-off value. The patients with the mean number of CD163 positive cells ≥ the cut-off value were those with high TAM infiltration, and vice versa. The association of TAM infiltration with clinicopathological features and prognosis was analyzed, and Cox proportional hazards model was used for multivariate analysis of survival.Results:The positive cell median number of CD163 in cardia carcinoma tissues was higher than that in adjacent tissues [the median number ( P25, P75): 32/high power field (HP) (16/HP, 46/HP) vs. 6/HP (4/HP, 11/HP)], and the difference was statistically significant ( Z = -35.044, P < 0.01). There were 48 cases in low invasive group (< 32/HP) and 52 cases in high invasive group (≥32/HP). The proportion of patients with high TAM infiltration in serosa and extraserosa was higher than that in mucosa and muscle [60.9% (39/64) vs. 36.1% (13/36)], and the proportion of patients with high TAM infiltration for patients with lymph node metastasis was higher than that for patients without lymph node metastasis [61.8% (42/68) vs. 31.3% (10/32)], and the proportion of patients with high TAM infiltration for those with TNM stage Ⅲ-Ⅳ was higher than that for those with TNM stage Ⅰ-Ⅱ [64.4% (38/59) vs. 34.1% (14/41)], and the differences were statistically significant (all P < 0.05). The median overall survival time of high TAM group was shorter than that of low TAM group [24.00 months (95% CI 17.25-43.50 months) vs. 62.00 months (95% CI 34.00-68.00)], and the difference in overall survival was statistically significant (χ 2 = 18.137, P < 0.01). Lymph node metastasis ( HR = 0.301, 95% CI 0.105-0.862, P = 0.025), TNM staging ( HR = 8.404, 95% CI 2.810-25.133, P < 0.01) and TAM infiltration level in cancer tissues ( HR = 4.277, 95% CI 2.372-7.712, P < 0.01) were independent influencing factors for overall survival of patients. Conclusions:TAM plays an important role in the invasion and metastasis of cardia carcinoma and can be used as an independent predictor of biological behavior and prognosis in cardia carcinoma.

Propensity score-matched analysis of clinical outcome after enucleation versus regular pancreatectomy in patients with small non-functional pancreatic neuroendocrine tumors.

OBJECTIVES: The effectiveness of enucleation in treatment for low-grade (G1, G2) small (≤2 cm) non-functional pancreatic neuroendocrine tumors (sNF-pNETs) remains controversial. This study investigated short- and long-term outcome of enucleation comparing with regular pancreatectomy in patients with sNF-pNETs. METHODS: The clinical data of patients with sNF-pNETs who underwent surgery in our hospital from January 2000 to December 2017 were retrospectively collected. Short- and long-term outcomes of two operations were analyzed. The propensity score matching (PSM) was performed to reduce potential selection bias. RESULTS: A total of 123 patients with sNF-pNETs were enrolled with 62 males, 69 G1, and median age was 56.91 ± 10.04 years old. During the follow-up period (mean 87 ± 58.1 months), 9(7.32%) disease progressed (recurrence or metastasis) and 2 died (1.62%), 5-years OS was 100%, 5-years DFS was 91.4%. Both lymph node metastasis (p = 0.117) and pathological grade (p = 0.050) were not prognostic factors for sNF-pNETs. The propensity score-matched cohort comprised 27 patients with enucleation and 44 patients with regular pancreatectomy. Enucleation was noninferior to regular pancreatectomy in terms of DFS, before or after PSM. The surgical duration (P < 0.01) and blood loss (P < 0.01) significantly decreased in enucleation compared with regular pancreatectomy. The other postoperative complications tended to occur in regular pancreatectomy than in enucleation, but no statistically significant difference (all p > 0.05). CONCLUSION: Enucleation seems to be an effective option for the treatment of sNF-pNETs with a lower total rate of postoperative complications and similar long-term prognosis, compared with regular pancreatectomy.

Research advances in molecular targeted therapy for gastroenteropancreatic neuroendocrine neoplasms / 中华消化外科杂志

Neuroendocrine neoplasms, commonly deriving from neuroendocrine cells of gastrointestinal tract and pancreas, are remarkably heterogeneous. As for gastroentero-pancreatic neuroendocrine neoplasms, surgery is the first choice for treatment, whereas molecular targeted therapy provides a new treatment option for patients with local advancement or metastases. Drugs for molecular targeted therapy used clinically include somatostatin analogs, mammalian target of rapamyoin pathway inhibitors, tyrosinekinase inhibitors, immunotherapy and so on. Research findings from experiments and clinic trials will possibly provide new therapeutic methods for molecular targeted therapy in the future.

A comparative analysis of clinical operation system and continuing education of pediatricians between Chinese and American children's hospitals / 中华医学教育探索杂志

For provincial children's hospitals and children's hospitals affiliated to medical colleges and universities with a high level of the diagnosis and treatment,they are the center of referral and need to retain pediatricians and build a high-level team of pediatricians.With the authors' own experience in Cincinnati Children's Hospital Medical Center in the US,this article briefly introduces the current clinical operation mode in American children's hospitals,especially the consultation system mainly composed of attending physicians and the mode of continuing medical education based on both clinical and scientific research.Such experience provides a reference for pediatricians in China.

Selection and application opportunity of antibiotics in children with respiratory tract infections / 中华实用儿科临床杂志

Respiratory tract infection is the most common disease in children, and it is also the most common disease of irrational use of antibiotics.The rational application of antibiotics is to reduce the rate of bacterial resistance and its adverse events.The emergence of drug-resistant strains is closely related to the wide application of antibiotics.In order to reduce the irrational use of antibiotics in children′s respiratory tract infection, pediatricians need to know the timing of application of antibiotics.The respiratory tract infection can be divided into upper respiratory tract infection and lower respiratory tract infection, including common cold, pharyngitis, sinusitis, otitis media, bronchitis and bronchitis, and pneumonia.This article reviews the application timing of antibiotics in the common respiratory tract infection of these children.

The value of preoperative CA19-9 combined with platelet-to-lymphocyte ratio in predicting invasive malignancy in intraductal papillary mucinous neoplasms / 中华外科杂志

Objective@#To explore preoperative predictive markers for invasive malignancy in intraductal papillary mucinous neoplasm(IPMN).@*Methods@#The retrospective case-controlled study was adopted.Seventy-nine patients who underwent surgery and with pathologically confirmed IPMN from January 2005 to December 2014 at Department of Pancreatic Surgery, Zhongshan Hospital Fudan University were enrolled.Forty-six patients were male and 33 were female,with an average age of (62.9±8.9)years (range:37-82 years).Tumor sites:56 tumors were located at the head of the pancreas,22 were located at the body and tail of the pancreas,and 1 was located across the whole pancreas.Surgical procedures: 51 patients underwent pancreaticoduodenectomy, 22 patients underwent distal pancreatectomy, 4 patients underwent segmental pancreatectomy and 2 patients underwent total pancreatectomy.IPMNs were classified into non-invasive lesions and invasive carcinomas according to the histopathological findings of the tumor.Thirty-two tumors were non-invasive lesions and 47 were invasive carcinomas.The preoperative findings were compared between patients with non-invasive IPMN and patients with invasive carcinoma by univariate analysis using t test and χ2 test accordingly,and factors with statistically significance were subsequently submitted to multivariate analysis.@*Results@#Univariate analysis showed that tumor size(P=0.022), carcinoembryonic antigen(P=0.012), CA19-9(P=0.011), lymphocytes(P=0.034), neutrophil-to-lymphocyte ratio(P=0.010)and platelet-to-lymphocyte ratio(PLR)(P=0.004)were predictive markers with statistical significance.Multivariate analysis showed that CA19-9(P=0.012)and PLR(P=0.025) were independent predictive markers for invasive malignancy in IPMN.The area under curve of the combination factor of CA19-9 and PLR(0.864) was larger than that of CA19-9(0.806) or PLR(0.685) alone, and all the authentic indicators of the combination factor were better than those of each alone.@*Conclusions@#CA19-9 and PLR are independent predictive markers for invasive malignancy in IPMN.The combination of CA19-9 and PLR has improved efficacy than each alone.

Selection and application opportunity of antibiotics in children with respiratory tract infections / 中华实用儿科临床杂志

Respiratory tract infection is the most common disease in children,and it is also the most common disease of irrational use of antibiotics.The rational application of antibiotics is to reduce the rate of bacterial resistance and its adverse events.The emergence of drug-resistant strains is closely related to the wide application of antibiotics.In order to reduce the irrational use of antibiotics in children's respiratory tract infection,pediatricians need to know the timing of application of antibiotics.The respiratory tract infection can be divided into upper respiratory tract infection and lower respiratory tract infection,including common cold,pharyngitis,sinusitis,otitis media,bronchitis and bronchitis,and pneumonia.This article reviews the application timing of antibiotics in the common respiratory tract infection of these children.

Combined test of serum CgA and NSE improved the power of prognosis prediction of NF-pNETs.

PURPOSE: Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs). PATIENTS AND METHODS: In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers' concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05. RESULTS: Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 µg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001). CONCLUSION: CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.

Clinical study of Chinese herbal prescription on lipid metabolic disorders in hemodialysis patients / 国际检验医学杂志

Objective To explore the clinical effect of traditional Chinese medicine on lipid metabolism dis-orders in hemodialysis patients.Methods 70 patients with hemodialysis received in the hospital from Novem-ber 2015 to April 2017 were enrolled in the study.They were randomly divided into control group and treat-ment group with 35 cases in each group.The control group was treated with simvastatin and and the treatment group was treated with self-made fat recipe combined with simvastatin.The levels of serum lipid ,serum in-flammatory cytokines ,renal function and liver function ,the total effective rate of treatment and the incidence of adverse reactions were compared between the two groups before and after treatment.Results There were no statistical significances in serum lipid indexes such as triglyceride (TG) ,total cholesterol (TC) ,high densi-ty lipoprotein cholesterol (HDL-C) ,low density lipoprotein cholesterol (LDL-C) ,C reactive protein (CRP) , interleukin 6 (IL-6) ,tumor necrosis factor α(TNF-α) and other serum inflammatory factors ,and renal func-tion indexes ,including urea nitrogen (BUN) ,creatinine (Scr) ,liver function indexes ,including alanine amin-otransferase (ALT) ,aspartate aminotransferase (AST) between two groups before treatment (P＞0.05) ;af-ter treatment ,the TG ,TC ,LDL-C ,CRP ,IL-6 ,TNF-α ,BUN ,Scr ,ALT and AST levels of the patients in the treatment group were significantly lower than those in the control group ;the HDL-C level of the patients in the treatment group was significantly higher than that in the control group ;the total effective rate of the treat-ment group was significantly higher than that in the control group ;the incidence of adverse reactions was sig-nificantly lower than that of the control group ,and the differences were statistically significant (P＞0.05). Conclusion The lipid-lowering effect of treatment of hemodialysis patients with traditional Chinese medicine lipid-lowering treatment is remarkable ,and worthy of promotion.

Prognostic analysis and clinicopathological features of 20 patients with appendiceal neuroendocrine neoplasms / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate clinicopathological features and prognostic factors of appendiceal neuroendocrine neoplasms(a-NEN).</p><p><b>METHODS</b>Clinical data of 20 patients diagnosed with a-NEN at Zhongshan Hospital of Fudan University between January 2000 and December 2016 were retrospectively analyzed. Pathological diagnosis was based on the WHO classification criteria of digestive system tumors (2010 edition). Based on the mitotic count and Ki-67 index, a-NENs were divided into grade 1 neuroendocrine tumor (NET G1), grade 2(G2) NET G2) and grade 3 (neuroendocrine carcinoma, NEC). Some special types of a-NEN (e.g. goblet cell carcinoid) and mixed adenoneuroendocrine neoplasms were classified as mixed adenoneuroendocrine carcinoma (MANEC). Follow-up was conducted by telephone or return visits. Univariate analysis was carried out using the Kaplan-Meier method, and the log-rank test was used to draw survival curves.</p><p><b>RESULTS</b>Of 20 patients, 14 were male and 6 were female with median age of 54 years. Seventeen cases presented acute right lower quadrant abdominal pain, 1 chronic right lower quadrant abdominal pain, 1 persistent abdominal discomfort with outburst whole abdominal pain and 1 was found during body check without symptoms. Twenty cases comprised 8 G1 patients, 4 G2 patients, 3 G3 patients, and 5 MANEC patients. When diagnosed, there was 1 patient with liver metastasis, 1 patient with abdominal and pelvic metastases, and 2 patients with postoperative pathological findings of lymph node metastasis. Six patients underwent appendectomy, 12 underwent right hemicolectomy, 1 underwent right hemicolectomy plus small intestine resection, and 1 underwent partial hepatectomy plus right hemicolectomy. The follow-up time was 7-187 months(average, 36 months). The total 1- and 3-year survival rates were 94.7% and 60.2%, respectively. Univariate analysis showed that age >50 years (χ=7.036, P=0.008), pathology grade as MANEC (χ=5.297, P=0.021), and metastasis (χ=6.558, P=0.010) indicated lower 5-year survival rate.</p><p><b>CONCLUSIONS</b>Most a-NEN patients have no typical symptoms, and the main complaint at consultation is acute right lower quadrant abdominal pain. Prognosis is poor for patients with age >50 years, MANEC pathology grade and metastasis.</p>

Application of peptide receptor radionuclide therapy for gastroenteropancreatic neuroendocrine tumor / 中华消化外科杂志

Peptide receptor radionuclide therapy (PRRT),being investigated as an effective treatment for inoperable gastroenteropancreatic neuroendocrine tumor,has gained much importance in recent years.With increasing data of clinical trials and the exploration of different radionuclides as well as the toxic and side effects,PRRT has developed continuously and play a marked role on the treatment of gastroenteropancreatic neuroendocrine tumor.

Treatment progression of rectal neuroendocrine neoplasms and hepatic metastasis / 中华消化外科杂志

Gastroenteropancreatic neuroendocrine neoplasms are a group of heterogeneous tumors originated from the gastrointestinal peptidergic neurons and neuroendocrine cells.Rectum is one of the major sites of gastroenteropancreatic neuroendocrine neoplasms.Although the progression of rectal neuroendocine neoplasms (rNENs) is relatively slow,metastasis could occurs and liver is the major target organ invaded by distant metastatic rNENs.Surgical operation can be used as the preferred method for the treatment of rNENs and its metastasis at present.If the clinical situations of tumors are not eligible for the operation,interventional treatment can be considered as an alternative treatment.The chemotherapies and molecule-targeted drugs for rNENs are primarily in the light of therapeutic methods for pancreatic neuroendocrine neoplasms,it may help patients achieve partial response or stable disease,and prolong patients survival time.However,there has been few clinical researches directed toward rNENs and no an extensive consensus for treatment of rNENs up to now,and more evidences of evidence-based medicine should be necessitated.This paper has discussed and summarized treatment progression of rNENs and its metastasis.

The value of preoperative NLR and PLR combined with the consensus in surgical decision making for branch duct intraductal papillary mucinous neoplasm of the pancreas / 中华普通外科杂志

Objective To analyze the difference among the 3 guidehnes used to make surgical decision for branch duct intraductal papillary mucinous neoplasm (BD-IPMN),then the guidelines were combined with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) respectively for further analysis.Methods Clinical data of 51 appropriate BD-IPMN patients who underwent surgical resection from January 2008 to December 2015 was retrospectively analyzed.Results The significant difference was exist in the consensus for followup criterion (P ＜ 0.05).The preoperative NLR and PLR were helpful for the differential diagnosis between malignant and benign BD-IPMN,because the receiver operating characteristic curve (ROC) of NLR and PLR for prediction were 0.686 and 0.692,and the best boundary values were 2.64,92.56 respectively.The consensus combined with PLR could improve the specificity and positive predictive value (PPV),besides,the specificity and PPV could achieve 70.3％,54.2％ respectively while the sensitivity (92.9％) still remained at an ideal level after international consensus guideline combined with PLR.Conclusions NLR ≥ 2.64 and PLR ≥ 92.56 were predictive markers for the presence of BD-IPMN associated invasive tumor.The addition of PLR as a criterion to the international consensus guideline improved the accuracy of international consensus guidelines in estimating invasive BD-IPMN.

The value of preoperative NLR and PLR combined with the consensus in surgical decision making for branch duct intraductal papillary mucinous neoplasm of the pancreas / 中华普通外科杂志

Objective To analyze the difference among the 3 guidehnes used to make surgical decision for branch duct intraductal papillary mucinous neoplasm (BD-IPMN),then the guidelines were combined with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) respectively for further analysis.Methods Clinical data of 51 appropriate BD-IPMN patients who underwent surgical resection from January 2008 to December 2015 was retrospectively analyzed.Results The significant difference was exist in the consensus for followup criterion (P ＜ 0.05).The preoperative NLR and PLR were helpful for the differential diagnosis between malignant and benign BD-IPMN,because the receiver operating characteristic curve (ROC) of NLR and PLR for prediction were 0.686 and 0.692,and the best boundary values were 2.64,92.56 respectively.The consensus combined with PLR could improve the specificity and positive predictive value (PPV),besides,the specificity and PPV could achieve 70.3％,54.2％ respectively while the sensitivity (92.9％) still remained at an ideal level after international consensus guideline combined with PLR.Conclusions NLR ≥ 2.64 and PLR ≥ 92.56 were predictive markers for the presence of BD-IPMN associated invasive tumor.The addition of PLR as a criterion to the international consensus guideline improved the accuracy of international consensus guidelines in estimating invasive BD-IPMN.

Detection and clinical application of circulating tumor cells in pancreatic neoplasm / 中华消化外科杂志

Pancreatic neoplasm is one of the most commonly-appeared digestive tumors and has been well-recognized as the poor diseases which have the difficulties in diagnosis,treatment and prognosis estimation.Recently,the detection of circulating tumor cells (CTCs) has been a pretty highlight of the research on detecting tumor cells in peripheral blood,and furthermore,the clinical value in the diagnosis,treatment and prognosis prediction has already been verified through a large amount of samples analyses in various kinds of tumor diseases.This paper aims to review and conclude the techniques of CTCs enrichment,detection and clinical implications in pancreatic neoplasms.In addition,the existing papers have been summarized and prospect of application of CTCs is also presented.

Tissue inhibitor of metalloproteinases 3 promoter methylation and mRNA expression in cardia carcinoma and its relationship with prognosis / 肿瘤研究与临床

Objective To explore the relationship of the methylation levels of tissue inhibitor of metalloproteinases 3 (TIMP-3) gene promoter CpG islands with the invasiveness and prognosis in cardia carcinoma. Methods The tumors tissues were collected from 65 patients with cardia carcinoma. The methylation levels of the promoter of TIMP-3 gene were detected by methylation-specific PCR (MSP), the mRNA expression levels of TIMP-3 gene were detected by RT-PCR. The relationship of TIMP-3 gene ectopic methylation with invasiveness and prognosis of the cardia carcinoma patients was analyzed. Results The positive expression rates of TIMP-3 mRNA in gastric cancer and normal gastric tissues were 53.8 % (35/65) and 96.9 % (63/65), respectively. The difference was not statistically significant(Fisher exact test, P=0.912). The positive rate of TIMP-3 mRNA was negatively correlated with the depth of tumor invasion and lymph node metastasis [mucosa and muscular vs. serosa and mucosa outside of the serosa and muscula: 83.3 % (10/12) vs. 45.3 % (24/53); with lymph node metastasis vs. without lymph node metastasis: 73.9 % (17/23) vs. 40.5 %(17/42)] (both P<0.05). There was a negative correlation between TIMP-3 gene promoter methylation and TIMP-3 mRNA expression (r=-0.276, P=0.026). The size of tumor and TIMP-3 gene promoter methylation were both the independent influencial factors of prognosis in cardia carcinoma (both P<0.05). Conclusion The methylation of promoter region in CpG islands plays an important role in the invasion and metastasis of cardia carcinoma, and it can be used as an independent predictor of biological behavior and prognosis.

The promoter methylation of tissue inhibitor of metalloproteinase 3 in cardia carcinoma and its clinical significance / 肿瘤研究与临床

Objective To explore the relations among the promoter methylation of tissue inhibitor of metalloproteinase-3 (TIMP-3) gene and its protein expression, and the clinicopathological features in the gastric cardia carcinoma. Methods The tumor tissues and the adjacent normal mucosal tissues were collected from 65 patients with cardia carcinoma. The promoter methylation levels and the protein expression of TIMP-3 gene were detected by methylation-specific PCR (MSP) and immunohistochemistry respectively. Results The TIMP-3 methylation rates was 78.5 % (51/65) in the tumor tissues and 13.8 % (9/65) in the incisal edge of normal tissues, the methylation rates of TIMP-3 had positive correlation with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. The protein expression of TIMP-3 was 26.2 %(17/65) in the tumor tissues and 95.4 % (62/65) in the incisal edge of normal tissues (P = 0.016), the protein expression of TIMP-3 was negatively correlated with the size of tumor, invasion depth, lymphatic metastasis and the stage of tumor. Conclusion The methylation of promoter region in CpG islands is a main mechanism of reduced and loss expression of TIMP-3 gene, which may play an important role in the invasion and metastasis of cardia carcinoma.

Pancreatic neuroendocrine carcinoma: clinicopathological characteristics and prognosis / 中华普通外科杂志

Objective To analyze the clinicopathological characteristics and the related factors influencing the prognosis of pancreatic neuroendocrine carcinoma.Methods The clinicpathological and follow-up data of 21 patients with pancreatic neuroendocrine carcinoma admitted between April 2000 and August 2013 in Zhongshan Hospital of Fudan University were analyzed retrospectively.The influence facts on patients' prognosis were analyzed statistically.Results Univariate analysis showed that age,stage,tumor size,degree of tumor differentiation and lymph node metastasis were factors separately influenced patients' survival.Multivariate analysis (Cox regression) revealed that age (P =0.019) was the only independent factor affecting the prognosis.Conclusions Patients with pancreatic neuroendocrine carcinoma were mostly non-functional and presented no specific clinical features.Tumors tended to metastasize and the prognosis was poor.Age was the independent factor affecting the prognosis.