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Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

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World Journal of Gastroenterology 2014年第42期20卷 15564-15579页

作者： Jeffrey M Sutton Daniel E Abbott department of Surgery Division of Surgical Oncology University of Cincinnati Medical Center

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

关键词： Pancreatic cancer Neoadjuvant therapy Chemotherapy Chemoradiation Biomarkers

Jejunal diverticulosis found in a patient with long-standing pneumoperitoneum and pseudo-obstruction on imaging:a case report

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Gastroenterology Report 2016年第4期4卷 337-340,I0003页

作者： Carolyn Hanna John Mullinax Mark S Friedman Julian Sanchez USF Morsani College of Medicine TampaFLUSA department of surgical oncology Moffitt Cancer CenterTampaFLUSA

Small bowel diverticulosis is a rare finding within the general population and jejunal diverticulosis,specifically,is even *** manifestations can range from post-prandial pain,constipation and malabsorption to serious complications,such as gastro-intestinal hemorrhage,perforation and acute intestinal *** we describe the case of an 81-yearold gentleman who presented with a three-year history of abdominal pain and weight *** unremarkable physical examination and laboratory tests,persistent pneumoperitoneum and dilated loops of small bowel were found on *** been given a diagnosis of small bowel bacterial overgrowth,the patient underwent capsule endoscopy study for further evaluation of his small *** capsule did not reach the colon and the patient never noted passing the capsule in his stool so,six months post-procedure,a computed tomography(CT)scan seemed to reveal the retained *** exploratory laparotomy revealed 200 cm of atonic,dilated jejunum with impressive diverticula along the antimesenteric *** case report is an example of an unusual set of presenting signs and symptoms of jejunal diverticulosis,including persistent pneumoperitoneum,pseudo-obstruction and small bowel bacterial overgrowth.A literature review has revealed that these signs have been present in other cases of jejunal diverticulosis,although the etiology and pathophysiology is not clearly understood.

关键词： Jejunal diverticulosis pneumoperitoneum pseudo-obstruction

Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer

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World Journal of Gastrointestinal oncology 2010年第1期2卷 19-30页

作者： PaulH Sugarbaker Kurt Vander Speeten O Anthony Stuart Washington cancer Institute Washington Hospital Center department of surgical oncology Ziekenhuis Oost-Limburg Schiepse Bos 6

The peritoneal surfaces of the abdomen and pelvis are important sites for the dissemination of gastrointestinal and gynecologic malignancy. Transcoelomic dissemination of cancer cells gives rise to carcinomatosis, which, without special treatment, is a fatal manifestation of these diseases. To treat peritoneal carcinomatosis, cytoreductive surgery removes gross disease plus perioperative intraperitoneal and perioperative intravenous chemotherapy eradicates microscopic residual disease and chemical compatibilities. Chemotherapy agents are administered either by the intraperitoneal or intravenous route, based on their pharmacologic properties. A peritoneal-plasma barrier, which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity, results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration of the intraperitoneal chemotherapy is facilitated by moderate hyperthermia (41-42℃). Targeting of intravenous chemotherapy to the peritoneal surface is facilitated by the intraperitoneal heat. A constant dose of chemotherapy agent and volume of carrier solution, based on body surface area, allows prediction of systemic drug exposure and systemic toxicity. Timing of the hyperthermic chemotherapy as a scheduled part of the surgical procedure to uniformly expose all peritoneal surfaces is crucial to success.

关键词： Intraperitoneal chemotherapy 5-fluorouracil Doxorubicin Mitomycin C Peritoneal-plasma barrier Appendiceal cancer Colorectal cancer Peritoneal mesothelioma Ovarian cancer

Study progression of anti-angiogenetic therapy and its combination with other agents for the treatment of advanced hepatocellular carcinoma

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Hepatobiliary Surgery and Nutrition 2018年第6期7卷 466-474页

作者： Xinlei Gong Shukui Qin department of Medical oncology PLA Cancer Center of Bayi Hospital Affiliated to Nanjing University of Chinese MedicineNanjing 210002China

Hepatocellular carcinoma(HCC)is a common malignancy worldwide and is especially prevalent in the Chinese *** of advanced HCC has posed a considerable challenge to clinicians and highly effective therapies remain *** contributes greatly to the pathogenesis,invasion and metastasis of ***,anti-angiogenesis therapy could be instrumental to the treatment of *** recent years,several anti-angiogenesis drugs have generated significant outcomes in a few key clinical studies,and in this light,anti-angiogenesis therapy has become a critical aspect of comprehensive treatment of *** this article,to provide a reference for clinicians,we review these advances and discuss the future direction of development.

关键词： Hepatocellular carcinoma(HCC) anti-angiogenesis treatment drugs research progress

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

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Chinese Journal of cancer Research 2017年第2期29卷 149-155页

作者： Liangze Zhang Weiwei Li Xiao Lyu Yan Song Yousheng Mao Shaoming Wang Jing Huang department of Thoracic surgical oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021 China department of Medical oncology the First Affiliated Hospital of Xinxiang Medical University Xinxiang 453100 China department of Medical oncology Central Hospital of Zibo Zibo 255036 China department of Medical oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021 China department of cancer Epidemiology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021 China

Objective： No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma （ESCC）. This is a study to explore the effect of postoperative paelitaxel （PTX） and cisplatin （DDP） in lymph node-positive, completely resected thoracic ESCC patients. Methods： We conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival （DFS） and overall survival （OS） were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. Results： Forty-three patients were accrued from December 2007 to May 2012 at cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 （86.0%） patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group （P=0.006）. The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group （P=0.013）. Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS （P=0.005）. Conclusions： Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.

关键词： Esophageal cancer adjuvant chemotherapy surgery paclitaxel cisplatin

Validation of clinical significance of examined lymph node count for accurate prognostic evaluation of gastric cancer for the eighth edition of the American Joint Committee on cancer(AJCC) TNM staging system

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Chinese Journal of cancer Research 2018年第5期30卷 477-491页

作者： Jingyu Deng Jinyuan Liu Wei Wang Zhe Sun Zhenning Wang Zhiwei Zhou Huimian Xu Han Liang department of Gastric cancer Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center of Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Cancer for Cancer department of Gastric and Pancreatic Surgery Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine department of surgical oncology the First Affiliated Hospital of China Medical University

Objective： To validate the necessity of increasing the examined lymph node （ELN） count for enhancing the accuracy of prognostic evaluation of gastric cancer （GC） patients after curative gastrectomy in multiple medical centers of ***： The clinicopathological data of 7,620 patients who underwent the curative resection for GC between 2001 and 2011 were included to demonstrate whether the ELN count is indispensable for enhancing the accuracy of prognostic evaluation of GC patients after surgery. After a meticulous stratification by using the cut-point survival analysis, all included 7,620 patients were allocated into three groups as： less than 16 （〈16）, between 16 and 30 （16-30）, and more than 30 （〉30） ELNs. Survival differences among various subgroups of GC patients were analyzed to assess the impact of the ELN count on the stage migration in accordance with the overall survival （OS） of GC ***： Survival analyses revealed that the ELN count was positively correlated with the OS （P：0.001） and was an independent prognostic predictor （P〈0.01） of 7,620 GC patients. Stratum analysis showed that the accuracy of prognostic evaluation could be enhanced when the ELN count was no less than 16 （≥16） for node-negative patients and 〉30 for node-positive patients. Stage migrations were mainly detected in the various subgroups of patients with specific pN stages as follows： pN0 with 16-30 ELNs （pN016-30） and pN0 with 〉30 ELNs （pN0〉30）, pN0 with 〈16 ELNs （pN0〈16） and pNl〉30, pNl〈l6 and pN216_30, pNl：6_30 and pN2〉30, pN3a〈l6 and pN3b16-30, and pN3a〈16 and pN3 b〉30. These findings indicate that increasing the ELN count is a prerequisite to guarantee precisely prognostic evaluation of GC ***： The ELN count should be proposed to be 〉30 for acquiring the accurate prognostic evaluadort for GC patients, especially for node-positive patients.

关键词： Stomach neoplasm lymph node metastasis prognosis

CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment

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World Journal of Clinical Cases 2023年第4期11卷 738-755页

作者： Zheng Li Xiao-Jie Zhang Chong-Yuan Sun He Fei Ze-Feng Li Dong-Bing Zhao department of Pancreatic and Gastric surgical oncology National Cancer Center/National Clinical Research for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the *** To determine the role of CD93 in *** Transcriptomic data of GC was investigated in a cohort from The cancer Genome ***,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the *** performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ***,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated *** Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in ***,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using *** CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the *** this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.

关键词： Gastric cancer CD93 Tumor microenvironment Immunotherapy Prognosis Biomarker

Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation?

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World Journal of Gastroenterology 2017年第46期23卷 8193-8199页

作者： Carrie Luu Marisa Amaral Jason Klapman Cynthia Harris Khaldoun Almhanna Sarah Hoffe Jessica Frakes Jose M Pimiento Jacques P Fontaine department of Thoracic oncology H. Lee Moffitt Cancer Center and Research Institute department of Gastrointestinal oncology H. Lee Moffitt Cancer Center and Research Institute department of Radiation oncology H. Lee Moffitt Cancer Center and Research Institute

AIM To evaluate the accuracy of endoscopic ultrasound(EUS) in early esophageal cancer(EC) performed in a highvolume tertiary cancer center. METHODS A retrospective review of patients undergoing esophagectomy was performed and patients with c T1 N0 and c T2 N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student's t test and Fisher's exact test or χ~2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS *** Between 2000 and 2015, 139 patients with clinical stage Ⅰ or Ⅱ?A esophageal cancer undergoing esophagectomy were identified. There were 25(18%) female and 114(82%) male patients. The tumor location included the middle third of the esophagus in 11(8%) and lower third and gastroesophageal junction in 128(92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients(21%) were under-staged by EUS; of those, 19(14%) had unrecognized nodal disease. Positron emission tomography(PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients(6%) in whom both EUS and PET were negative for nodal involvement. CONCLUSION EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.

关键词： Esophageal cancer Endoscopic ultrasound Staging Early esophageal cancer Endoscopic mucosal resection

Advances in the management of peritoneal mesothelioma

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World Journal of Gastroenterology 2014年第33期20卷 11700-11712页

作者： Ali Raza Wei-Ching Huang Kazuaki Takabe Division of surgical oncology Department of Surgery Virginia Commonwealth University School of Medicine and Massey Cancer Center Richmond VA 23298-0011 United States

Malignant peritoneal mesothelioma(PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction(CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Ac-cordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1(SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease.

关键词： Peritoneal mesothelioma Mesothelioma Hyperthermic intraperitoneal chemotherapy Cytore-duction Sphingosine kinase Sphingosine-1-phosphate FTY720