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Potential indicators predict progress after surgical resection of gastrointestinal stromal tumors

null

《医学前沿（英文）》 2012年 第6卷 第3期   页码 317-321 doi: 10.1007/s11684-012-0203-9

摘要：

In order to find out the potential indicators predicting prognosis of malignant gastrointestinal stromal tumors (GISTs) after surgical resection, we collected clinical records of 80 patients with malignant GISTs. Tumor location, size, mitotic index, necrosis were compared with the prognosis of malignant GISTs by Kaplan-Meier method and log-rank test. After a median follow-up of 844 days (52–2 145), we found that as National Institutes of Health suggested, tumors with intermediate risk had more favorable prognosis than that with high risk. Their 3-year survival rate were 65.3% and 41.3%, respectively (P<0.001). Moreover, tumor size and mitotic index were associated with free survival. The 3-year survival rate for patients with tumor size≤10 cm and>10 cm were 62.3% and 41.8%, respectively (P = 0.002), Tumors with mitotic index≤5/50 HPF had a higher 3-year survival rate than tumors with mitotic index>5/50 HPF (67.1% versus 40.7%, P = 0.005). The presence of necrosis was directly related to the malignant behavior. The 3-year survival rate for presence and absence necrosis were 50.8% and 64.8% (P = 0.008). From the present study, we can conclude that besides tumors size and mitotic index, tumor location and necrosis also influence on the long-term survival of patient with malignant GISTs after surgical resection.

关键词： gastrointestinal stromal tumors     surgery     survival    

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Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumors: a study of

LIANG Yumei, LI Xianghong, LU Youyong, LV Yali, ZHONG Mei, PU Xiaolu, LI Wenmei

《医学前沿（英文）》 2008年 第2卷 第1期   页码 87-94 doi: 10.1007/s11684-008-0016-z

摘要： The biological behavior of gastrointestinal stromal tumors (GISTs) are highly variable. To investigate the biological behavior of GIST, we collected 83 cases of gastric and 62 cases of small intestinal GIST from the Department of Pathology of the Chinese PLA General Hospital. The parameters include age, primary tumor location, tumor diameter, mitotic index, tumor necrosis, risk assessment, clinical stage and the exon 11 mutation. All these were analyzed in 105 cases along with the follow-up data and tested by log rank and COX hazard proportional model. We find that the average age of gastric GIST was 55.4 years. Of the 62 cases that were followed up, 17 cases had metastasis or recurrence and the 5-year survival rate was (66.51 ± 17.06)%. For the small intestinal GIST, the average age was 50.6 years and 43 cases were followed up. Of these, 22 cases had metastasis or recurrence and the 5-year survival rate was (61.76 ± 18.30)%. Small intestinal GIST was more frequently associated with metastasis and tumor relapse than gastric GIST ( = 6.131, = 0.013). For gastric GIST, patients younger than 50 years ( = 0.046), the advanced clinical stage ( = 0.0001), the large tumor diameter ( = 0.0001), a high mitotic index ( = 0.0001), necrosis ( = 0.0001) and a high risk grade ( = 0.004) were all correlated with a lower survival rate. The COX hazard proportional model revealed that advanced clinical stage ( = 0.001), large tumor size ( = 0.001), a high mitotic index ( = 0.002) and the high risk grade ( = 0.018) indicated a poorer prognosis in gastric GIST. For small intestinal GIST, necrosis ( = 0.036) and advanced clinical stage ( = 0.010) were associated with lower survival rates and the clinical stage was shown to be an independent prognostic indicator. A total of 25 cases harbored mutations in exon 11. The frequency of mutation was 32% and 22.5% for gastric and small intestinal GIST, respectively. In gastric GIST, the mutated was predominant in patients older than 50 years of age. But in the small intestinal GIST, the mutated was predominant in the age group of 40–49 years. In conclusion, for gastric GIST, clinical stage, tumor size, mitotic index, and risk grade are the prognostic indicators. For small intestinal GIST, necrosis and clinical stage are the prognostic indicators. Small intestinal GIST are more aggressive than gastric GIST. The occurrence of mutation may correlate with the age of patients.
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A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 108-111 doi: 10.1007/s11684-014-0344-0

摘要：

Hemoperitoneum is a rare and potentially life-threatening complication of GIST. We reported a 54-year-old man who developed disseminated intra-abdominal recurrence from a previously resected gastrointestinal stromal tumour (GIST) of the small bowel, and the patient presented with hemoperitoneum. Emergent debulking surgery was performed. A high dose imatinib was prescribed. Despite the presence of residual disease, the patient was well clinically 8 months after the operation. Even though, there is no evidence to support the routine use of debulking surgery in the management of GIST. In our patient, disease progression after second line targeted therapy and the absence of alternative treatment options for spontaneous rupture and hemoperitoneum prompted us to treat the patient aggressively. Resection of the ruptured GIST was carried out for control of bleeding and to prevent recurrent bleeding in this patient with good surgical risks. During the treatment decision-making, the patient’s general condition, the risk of surgery and the extent of dissemination were taken into consideration. In this patient who presented with spontaneous rupture of a small intestinal GIST, the novel use of targeted therapy and aggressive surgical treatment produced reasonably good survival outcome.

关键词： gastrointestinal stromal tumour     hemoperitoneum     small bowel GIST     small bowel neoplasm     imatinib    

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Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely

Bin Yang, Yan Yu, Jing Chen, Yan Zhang, Ye Yin, Nan Yu, Ge Chen, Shifei Zhu, Haiyan Huang, Yongqun Yuan, Jihui Ai, Xinyu Wang, Kezhen Li

《医学前沿（英文）》 2018年 第12卷 第5期   页码 509-517 doi: 10.1007/s11684-017-0554-3

摘要：

This study was performed to evaluate the oncological and reproductive outcomes of childbearing-age women treated with fertility-sparing surgery (FSS) for non-epithelial ovarian tumors in China. One hundred and forty eight non-epithelial ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015 from two medical centers in China were identified. Progression-free survival (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis suggested that delivery after treatment is related to PFS (P=0.023), whereas histology significantly influenced OS. Cox regression analysis suggested that only histology was associated with PFS and OS (P<0.05). Among the 129 women who completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44 women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including 35 live births without birth defects. Non-epithelial ovarian tumors can achieve fulfilling prognosis after FSS and chemotherapy. Histology might be the only independent prognostic factor for PFS and OS. FSS followed by ACT appeared to have little or no effect on fertility. Meanwhile, postoperative pregnancy did not increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not beneficial for fertility.

关键词： malignant germ cell tumors     ovarian sex cord-stromal tumors     fertility-sparing surgery     prognosis     fertility    

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Rare tumors: a blue ocean of investigation

《医学前沿（英文）》 2023年 第17卷 第2期   页码 220-230 doi: 10.1007/s11684-023-0984-z

摘要： Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients’ prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

关键词： rare tumors     diagnosis flowchart     treatment strategy     clinical trials recommendation    

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Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 20-31 doi: 10.1007/s11684-016-0493-4

摘要：

To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.

关键词： gastrointestinal fluid     gastric carcinoma     biomarker     diagnosis     prognosis     gastrectomy     adverse events    

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Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

《化学科学与工程前沿（英文）》 2022年 第16卷 第3期   页码 333-344 doi: 10.1007/s11705-021-2059-5

摘要： Compared to conventional hyperthermia that is limited by low selectivity and severe side effects, nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment. Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia, which introduces a new avenue, allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery, i.e., long-lasting and/or systemic anti-tumor immunity. This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia. This includes the discussion about underlying mechanism such as immunogenic cell death, which initiates a profound immunological chain reaction. In order to propagate the immune activation as a viable therapeutic principle, we further discussed the tumor type-specific complexity in the immunological tumor microenvironment, including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.

关键词： nano-enabled hyperthermia     immunogenic cell death     heterogeneous immunological landscape     tumor microenvironment    

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Minimal residual disease in solid tumors: an overview

《医学前沿（英文）》 2023年 第17卷 第4期   页码 649-674 doi: 10.1007/s11684-023-1018-6

摘要： Minimal residual disease (MRD) is termed as the small numbers of remnant tumor cells in a subset of patients with tumors. Liquid biopsy is increasingly used for the detection of MRD, illustrating the potential of MRD detection to provide more accurate management for cancer patients. As new techniques and algorithms have enhanced the performance of MRD detection, the approach is becoming more widely and routinely used to predict the prognosis and monitor the relapse of cancer patients. In fact, MRD detection has been shown to achieve better performance than imaging methods. On this basis, rigorous investigation of MRD detection as an integral method for guiding clinical treatment has made important advances. This review summarizes the development of MRD biomarkers, techniques, and strategies for the detection of cancer, and emphasizes the application of MRD detection in solid tumors, particularly for the guidance of clinical treatment.

关键词： MRD     solid tumor     CTC     ctDNA    

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Immunotherapy-based combination strategies for treatment of gastrointestinal cancers: current status

Chenfei Zhou, Jun Zhang

《医学前沿（英文）》 2019年 第13卷 第1期   页码 12-23 doi: 10.1007/s11684-019-0685-9

摘要：

Strategies in comprehensive therapy for gastrointestinal (GI) cancer have been optimized in the last decades to improve patients’ outcomes. However, treatment options remain limited for late-stage or refractory diseases. The efficacy of immune checkpoint inhibitors (ICIs) for treatment of refractory GI cancer has been confirmed by randomized clinical trials. In 2017, pembrolizumab was approved by the US Food and Drug Administration as the first agent for treatment of metastatic solid tumors with mismatch repair deficiency, especially for colorectal cancer. Given the different mechanisms, oncologists have focused on determining whether ICIs-based combination strategies could achieve higher efficacy than conventional therapy alone in late-stage or even front-line treatment of GI cancer. This review discusses the current status of combining immune checkpoint inhibitors with molecular targeted therapy, chemotherapy, or radiotherapy in GI cancer in terms of mechanisms, safety, and efficacy to provide basis for future research.

关键词： gastrointestinal cancer     immune checkpoint inhibitor     combination therapy    

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Gastrointestinal damage caused by swallowing multiple magnets

null

《医学前沿（英文）》 2012年 第6卷 第3期   页码 280-287 doi: 10.1007/s11684-012-0207-5

摘要：

Swallowing multiple magnets is not uncommon worldwide and it frequently leads to serious consequences. However, most patients fail to receive timely and correct diagnosis and treatment. A literature search was performed to establish an algorithm for these accidents by the authors to identify relevant articles published from June 1987 to October 2010 in Google, Medline, ISI Web of Knowledge Ovid, CNKI, Korea Med and library document delivery, using search terms “magnet ingestion, ” “fistula, ” and “perforation. ” A total of 149 patients with ingestion of magnetic foreign bodies from 20 countries and areas were identified. 22 of them were companioned with neurological and psychiatric disorders. Swallowing magnets occurred throughout childhood and adolescent, mostly ranging 2 to 4 years in age. Various gastrointestinal damages such as necrosis and intestinal perforation or fistula were encountered. Damage from swallowing multiple magnets carries a significant risk of morbidity and even mortality throughout childhood to adolescent worldwide. Older children and adults with neurological and psychiatric problems may be at high risk for such accidents. Early intervention is crucial.

关键词： magnet     ingestion     fistula     perforation    

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Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

《医学前沿（英文）》   页码 805-822 doi: 10.1007/s11684-023-1025-7

摘要： Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.

关键词： CTLA-4     PD-1     PD-L1     immune checkpoint blockade (ICB)     metabolic reprogramming     combined tumor therapeutic strategies    

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Molecular targeted therapy of gynecological malignant tumors: the development and challenge, from laboratory

Pengming SUN PhD, MD , Jalid SEHOULI PhD, MD , Lihui WEI BM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 256-264 doi: 10.1007/s11684-009-0052-3

摘要： More and more molecular drugs based on targeted therapy have been utilized in the treatment of gynecologic cancer, especially in ovarian cancer. In this article, we systematically review the current targeted therapeutic trials running in clinic. Large, randomized trials have been conducted in the treatment of ovarian cancer, endometrial cancer and cervical cancer by using small molecule, antisense, mutational gene as well as antibodies. Other planned or ongoing trials currentlytargeted at molecular markers which may play important roles in gynecological carcinogenesis andprogression suggest that combination chemotherapy with molecular targeted therapy will ultimately be an importantoption.

关键词： target therapy     gynecologic malignant tumors     clinical trail     molecular medicine    

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Detecting genetic hypermutability of gastrointestinal tumor by using a forensic STR kit

Anqi Chen, Suhua Zhang, Jixi Li, Chaoneng Ji, Jinzhong Chen, Chengtao Li

《医学前沿（英文）》 2020年 第14卷 第1期   页码 101-111 doi: 10.1007/s11684-019-0698-4

摘要： Growing evidence suggests that somatic hypermutational status and programmed cell death-1 overexpression are potential predictive biomarkers indicating treatment benefits from immunotherapy using immune checkpoint inhibitors. However, biomarker-matched trials are still limited, and many of the genomic alterations remain difficult to target. To isolate the potential somatic hypermutational tumor from microsatellite instability low/microsatellite stability (MSI-L/MSS) cases, we employed two commercial kits to determine MSI and forensic short tandem repeat (STR) alternations in 250 gastrointestinal (GI) tumors. Three types of forensic STR alternations, namely, allelic loss, Aadd, and Anew, were identified. 62.4% (156/250) of the patients with GI exhibited STR alternation, including 100% (15/15) and 60% (141/235) of the microsatellite high instability and MSI-L/MSS cases, respectively. 30% (75/250) of the patients exhibited STR instability with more than 26.32% (26.32%–84.21%) STR alternation. The cutoff with 26.32% of the STR alternations covered all 15 MSI cases and suggested that it might be a potential threshold. Given the similar mechanism of the mutations of MSI and forensic STR, the widely used forensic identifier STR kit might provide potential usage for identifying hypermutational status in GI cancers.

关键词： mismatch repair protein deficiency (MMR-D)     microsatellite instability (MSI)     short tandem repeats (STR)     gastrointestinal tumor     hypermutability    

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High frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas

《医学前沿（英文）》   页码 907-923 doi: 10.1007/s11684-023-1009-7

摘要： The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

关键词： FAK6/7     SRRM4     neuroendocrine neoplasms     pancreas     breast    

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Ingestible wireless capsules for enhanced diagnostic inspection of gastrointestinal tract

Mahdi RASOULI, Andy Prima KENCANA, Van An HUYNH, Eng Kiat TING, Joshua Chong Yue LAI, Kai Juan WONG, Su Lim TAN, Soo Jay PHEE

《机械工程前沿（英文）》 2011年 第6卷 第1期   页码 40-44 doi: 10.1007/s11465-011-0204-4

摘要：

Wireless capsule endoscopy has become a common procedure for diagnostic inspection of gastrointestinal tract. This method offers a less-invasive alternative to traditional endoscopy by eliminating uncomfortable procedures of the traditional endoscopy. Moreover, it provides the opportunity for exploring inaccessible areas of the small intestine. Current capsule endoscopes, however, move by peristalsis and are not capable of detailed and on-demand inspection of desired locations. Here, we propose and develop two wireless endoscopes with maneuverable vision systems to enhance diagnosis of gastrointestinal disorders. The vision systems in these capsules are equipped with mechanical actuators to adjust the position of the camera. This may help to cover larger areas of the digestive tract and investigate desired locations. The preliminary experimental results showed that the developed platform could successfully communicate with the external control unit via human body and adjust the position of camera to limited degrees.

关键词： wireless capsule endoscopy     ingestible medical device     in-body medical device     miniature actuator     medical robot     medical imaging    

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标题 作者 时间 类型 操作

Potential indicators predict progress after surgical resection of gastrointestinal stromal tumors

null

期刊论文

Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumors: a study of

LIANG Yumei, LI Xianghong, LU Youyong, LV Yali, ZHONG Mei, PU Xiaolu, LI Wenmei

期刊论文

A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

期刊论文

Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely

Bin Yang, Yan Yu, Jing Chen, Yan Zhang, Ye Yin, Nan Yu, Ge Chen, Shifei Zhu, Haiyan Huang, Yongqun Yuan, Jihui Ai, Xinyu Wang, Kezhen Li

期刊论文

Rare tumors: a blue ocean of investigation

期刊论文

Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

null

期刊论文

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

期刊论文

Minimal residual disease in solid tumors: an overview

期刊论文

Immunotherapy-based combination strategies for treatment of gastrointestinal cancers: current status

Chenfei Zhou, Jun Zhang

期刊论文

Gastrointestinal damage caused by swallowing multiple magnets

null

期刊论文

Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

期刊论文

Molecular targeted therapy of gynecological malignant tumors: the development and challenge, from laboratory

Pengming SUN PhD, MD , Jalid SEHOULI PhD, MD , Lihui WEI BM ,

期刊论文

Detecting genetic hypermutability of gastrointestinal tumor by using a forensic STR kit

Anqi Chen, Suhua Zhang, Jixi Li, Chaoneng Ji, Jinzhong Chen, Chengtao Li

期刊论文

High frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas

期刊论文

Ingestible wireless capsules for enhanced diagnostic inspection of gastrointestinal tract

Mahdi RASOULI, Andy Prima KENCANA, Van An HUYNH, Eng Kiat TING, Joshua Chong Yue LAI, Kai Juan WONG, Su Lim TAN, Soo Jay PHEE

期刊论文