Advances in medical treatment for pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanNENs,systemic treatment options vary due to the different differentiations,grades and stages.The available options for systemic therapy include somatostatin analogs,molecularly targeted agents,cytotoxic chemotherapeutic agents,immune checkpoint inhibitors,and peptide receptor radionuclide therapy.In addition,the development of novel molecularly targeted agents is currently in progress.The sequence of selection between different chemotherapy regimens has been of great interest,and resistance to chemotherapeutic agents is the major limitation in their clinical application.Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents.Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors,and greater therapeutic efficacy may be achieved by emerging radiolabeled peptides.Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity,dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy.Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments.In the future,the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Current gene therapy for stomach carcinoma

Gastric cancer is common in China [1-42],and its early diagnosis and treatment in advanced stage are difficult [31-50].In recent years ,gene study in cancer is a hotspot ,and great progress has been achieved [41-80] .Cancer gene therapy has shifted from the imagination into the laboratory and clinical trials.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

心胃同治法治疗高血压病探析

心与胃具有生理功能及病理变化上的联系,而心胃的功能状态均与高血压的形成密切相关。心主血脉,而脾胃为水谷之海,心胃共同影响着血液的生成运行及血管的和畅通利。“心胃同治”法通过恢复心胃的生理机能,保证气机的升降平衡,调整水谷津液的代谢来改善心血管的病理状态,从而治疗高血压。从“心胃同治”出发,探讨高血压的形成机制,并归纳出相应的治疗策略,为临床提供参考。

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

胃癌(GC)是极具异质性和侵袭性的消化系统恶性肿瘤之一,传统化疗药物及曲妥珠单抗等人表皮生长因子受体2(HER2)靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此,研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷,但在某些情况下无效或产生耐药,这与HER2在某些GC细胞中低表达有关,HER2低表达(HER2 IHC1+或IHC2+/ISH-)约占全部类型的40%~60%,但在临床实践中,这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物(ADC)的出现为HER2阳性GC提供了新的治疗选择,凭借其精准高效的抗肿瘤作用,有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性,相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述,并讨论HER2靶向ADC在应用和研发过程中面临的挑战。

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients

AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy（sTPN+5-Fu）,while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu（-MetTPN+5-Fu）.Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry（FCM）.Bloodsamples were taken to measure the serumprotein,methionine（Met）and cysteine（Cys）levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG0/G1 tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.

Neoadjuvant chemotherapy vs upfront surgery for gastric signet ring cell carcinoma:A retrospective,propensity score-matched study

BACKGROUND The benefit of neoadjuvant chemotherapy for patients with signet-ring cell carcinoma of the stomach is controversial.AIM To evaluate the perioperative and long-term outcomes of neoadjuvant chemotherapy for locally advanced gastric signet-ring cell carcinoma.METHODS This retrospective study identified patients with locally advanced signet-ring cell carcinomas of the stomach(cT3/4 and cN any)diagnosed from January 2012 to December 2017 by using the clinical Tumor-Node-Metastasis(cTNM)staging system.We performed 1:1 propensity score matching(PSM)to reduce bias in patient selection.The histologic and prognostic effects of neoadjuvant chemotherapy were assessed.The overall survival rates were used as the outcome measure to compare the efficacy of neoadjuvant chemotherapy vs surgery-first treatment in the selected patients.RESULTS Of the 144 patients eligible for this study,36 received neoadjuvant chemotherapy,and 108 received initial surgery after diagnosis.After adjustment by PSM,36 pairs of patients were generated,and baseline characteristics,including age,sex,American Society of Anesthesiologists score,tumor location,and cTNM stage,were similar between the two groups.The R0 resection rates were 88.9%and 86.1%in the surgery-first and neoadjuvant chemotherapy groups after PSM,respectively(P=1.000).The median follow-up period was 46.4 mo.The 5-year overall survival rates of the neoadjuvant chemotherapy group and surgery-first group were 50.0%and 65.0%(P=0.235),respectively,before PSM and 50%and 64.7%(P=0.192),respectively,after PSM.Multivariate analyses conducted before and after PSM showed that NAC was not a prognostic factor.CONCLUSION Neoadjuvant chemotherapy provides no survival benefit in patients with locally advanced gastric signet-ring cell carcinoma.For resectable gastric signet-ring cell carcinoma,upfront surgery should be the primary therapy.

Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

Personalized medicine in gastric cancer:Where are we andwhere are we going?

Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2(HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer.

Expression of bcl-2 oncogene in gastric precancerous lesions and its correlation with syndromes in traditional Chinese medicine

AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM).METHODS: Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied, including 39 cases of moderate gastric mucosal dysplasia, 19 casesof severe gastric mucosa dysplasia, g cases of incompletecolon metaplasia. In syndrome differentiation of TCM, 17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene weredetected by labeled streptavidin biotin (LSAB) immunohistochemistry and in situ hybridization respectively. RESULTS: Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL, which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia, there was no difference in the expression of bcl-2 oncogene (P＞0.05). In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation → stomach heat → blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bd-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: χ2 = 8.45, P＜0.05; the level of mRNA: χ2 = 7.35,P＜0.05).CONCLUSION: Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL, which correlates with different accompanying syndromes in TCM.

Auricular-Plaster Therapy Plus Acupuncture at Zusanli for Postoperative Recovery of Intestinal Function

以便在腹部手术以后由于胃肠的机能障碍减轻腹的扩张和另外的不快，病人被耳灰浆的治疗在 Zusanli (圣 36 ) 加针灸对待。(92.4%) 当在 13，控制的情况组织，这是 46.1% 时， 12 在操作以后在 72 个小时以内在治疗的 13 个盒子组织正常蠕动的显示出的恢复，显示加在 Zusanli (圣 36 ) 的针灸的那耳灰浆的治疗可以支持肠的功能的手术后的恢复。

POTENTIATION OF DOCETAXEL ANTITUMOR ACTIVITY BY BATIMASTAT AGAINST MOUSE FORESTOMACH CARCINOMA

Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB 94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. Methods and results. In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB 94 on MFC cell showed that docetaxel but not BB 94 had a significant cytotoxicity, and the effect of docetaxel wasn’t enhanced by BB 94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20mg/kg; doxorubicin: 6mg/kg) every 4 days for 3 injections (q4d×3), even that of BB 94 (30mg/kg i.p. qd×20) was observed. Tumor growth inhibition was greater for docetaxel batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB 94 (33.0%), and the effect of docetaxel could be potentiated by BB 94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log10 tumor cell kill. Conclusion. Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB 94 enchances the antitumor activity of docetaxel.

Retrovirus-mediated antisense RNA to bcl-2 alter the biological behavior of stomach carcinoma MGC-803 cell lines

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肠内营养对晚期胃癌化疗患者营养指标的影响

目的 研究肠内营养对晚期胃癌化疗患者营养指标的影响。方法 选取2020年1月至2022年1月40例晚期胃癌化疗患者作为研究对象,采用随机数字表法分为对照组(20例)与研究组(20例)。给予对照组患者常规化疗方案治疗,研究组患者在对照组的基础上联合肠内营养治疗,2组患者均连续治疗42 d。比较2组患者治疗前后身体测量指标、生活质量及营养指标情况。结果 与治疗前相比,治疗后研究组患者右上臂周围、左上臂周围、体重指数(BMI)、血红蛋白(Hb)、白蛋白(ALB)、转铁蛋白(TF)、前清蛋白(PA)水平升高,对照组患者右上臂周围、左上臂周围、BMI、血Hb、ALB、TF、PA水平降低,研究组高于对照组;与治疗前相比,治疗后2组患者躯体功能、角色功能、情绪功能、认知功能和社会功能评分降低,其中研究组高于对照组(P值均<0.05)。结论 肠内营养可有效缓解晚期胃癌化疗患者可有效缓解营养不良症状,改善生活质量,优化营养状态指标和提高预后。

乳腺癌患者内分泌治疗依从性常见问题及改善策略的研究进展

该文阐述了乳腺癌患者内分泌治疗依从性常见问题及改善依从性行为的干预措施,以期为医护人员制订乳腺癌患者内分泌治疗依从性管理方案提供参考依据。

穴位注射新斯的明用于胃癌腹腔镜根治术后快速康复管理中的价值

【目的】探讨穴位注射用于胃癌腹腔镜根治术后快速康复管理中的价值。【方法】将80例行胃癌腹腔镜根治术患者随机分为两组,每组40例,观察组在围术期行快速康复外科(FTS)管理的基础上加用足三里穴位注射新斯的明,对照组仅围术期实施FTS管理。比较两组手术相关指标,不同时点血清C反应蛋白(CRP)、白蛋白(ALB)水平及T淋巴细胞水平,比较两组不良反应发生情况和12个月生存情况。【结果】观察组下床活动时间、肛门排气时间、首次经口流质饮食时间、住院时间均显著少于对照组(P<0.05)。两组术后1 d、3 d的血清CRP水平显著高于术前,血清ALB水平显著低于术前(P<0.05);两组术后3 d血清CRP水平显著低于术后1 d,ALB水平显著高于术后1 d(P<0.05);观察组术后不同时点血清CRP水平显著低于对照组,血清ALB水平显著高于对照组(P<0.05)。两组术后3 d的CD3^(+)、CD4^(+)、CD8^(+)均显著低于本组术前(P<0.05);两组术后3 d的CD4^(+)/CD8^(+)与本组术前比较,差异均无统计学意义(P>0.05);观察组术后3 d的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)均显著高于对照组(P<0.05)。观察组不良反应总发生率显著低于对照组(P<0.05)。两组患者术后12个月生存率比较,差异无统计学意义(P>0.05)。【结论】在采用FTS管理的基础上加用足三里穴位注射新斯的明有助于腹腔镜胃癌根治术后患者更快康复,减轻机体对刺激的应激反应,改善患者的营养状态,调控机体免疫功能,降低不良反应发生率。

药物治疗管理在结直肠肿瘤病人围手术期营养支持治疗中的实践

目的评价临床药师运用药物治疗管理参与结直肠肿瘤病人围手术期营养支持治疗的效果,探索临床药师如何运用药物治疗管理为结直肠肿瘤病人围手术期提供更满意的药学服务。方法选取2019年1月至2020年3月黄山市人民医院收治的100例行结直肠癌根治术的病人,采用随机数字表法分为对照组和试验组,各50例。对照组由临床医师和护士负责病人的围手术期营养治疗管理,试验组由临床药师应用药物治疗管理对病人围手术期营养治疗进行干预。比较两组病人术后营养状况,临床疗效,治疗依从性和不良反应发生率。结果与对照组相比,试验组病人术后第7天营养指标血红蛋白,白蛋白、视黄醇结合蛋白水平提高,炎症指标C反应蛋白水平降低(P<0.05);术后7 d营养风险发生率试验组(8/50,16%)低于对照组(18/50,36%)(P<0.05);试验组术后出现并发症发生率(7/50,14%)和药物不良反应发生率(4/50,8%)低于对照组(22/50,44%)(15/50,30%)(P<0.05);治疗依从性良好率试验组(42/50,84%)优于对照组(18/50,36%)(P<0.05);住院天数试验组(18.22±4.71)d少于对照组(22.58±8.45)d(P<0.05)。结论药物治疗管理在围手术期病人营养支持治疗中的应用,可以有效改善病人围手术期营养情况,提高用药依从性,降低药物不良反应发生率,促进病人术后早期康复。

新辅助治疗对胃癌病人行机器人全胃切除术近期疗效影响

目的比较胃癌病人行单纯机器人全胃切除术(robotic total gastrectomy,RTG)与新辅助治疗后机器人全胃切除术(neoadjuvant therapy-robotic total gastrectomy,NAT-RTG)的近期疗效,探究采用新辅助治疗与否对RTG术后并发症的影响。方法回顾性分析2017年4月至2022年10月期间于解放军总医院第一医学中心普通外科医学部接受RTG的146例病人临床与病理信息,其中NAT-RTG组43例,单纯RTG组103例。比较两组病人围手术期指标与术后并发症情况,并采用二元Logistic回归分析RTG术后并发症的危险因素。结果与单纯RTG组相比,NAT-RTG组术后住院时间显著延长,差异有统计学意义[12.0(10.0,15.0)d比10.0(9.0,13.0)d,P=0.036]。NAT-RTG组与单纯RTG组以下指标比较差异均无统计学意义:手术时间[(279.0±56.0)min比(270.4±57.7)min,P=0.407],术中出血量[200(100,200)mL比100(100,200)mL,P=0.422],肿瘤R0切除率(90.7%比95.1%,P=0.308),淋巴结清扫数目[(26.2±12.3)个比(30.0±13.3)个,P=0.108],术后首次肛门排气时间[5.0(3.0,6.0)d比4.0(4.0,5.0)d,P=0.171],手术费用[(6.96±1.04)万元比(6.95±1.07)万元,P=0.984]及住院费用[(14.79±3.56)万元比(14.70±5.00)万元,P=0.908]。术后并发症方面,NAT-RTG组相比于单纯RTG组术后总体并发症发生率较高(34.9%比21.4%),但差异无统计学意义(P=0.087);在严重并发症发生率方面,NAT-RTG与RTG组差异无统计学意义(2.3%比3.9%,P=1.000)。单因素与多因素分析结果表明,女性[OR=4.019,95%CI(1.605,10.062),P=0.003]以及肿瘤长径≥3 cm[OR=3.121,95%CI(1.021,9.536),P=0.046]是影响RTG病人术后并发症发生的独立危险因素(P<0.05)。新辅助治疗不是影响RTG术后并发症的独立危险因素[OR=2.204,95%CI(0.912,5.325),P=0.079]。结论NAT-RTG与单纯行RTG近期疗效相当,但由于NAT-RTG仍有潜在增加术后并发症的风险,建议进行充分的术前评估与优化围手术期诊疗决策。此外,对于女性、肿瘤长径≥3 cm且需行RTG的病人,应重视术前筛查与评估,以减少围手术期并发症发生可能。