Multimodality approach for locally advanced esophageal cancer

Carcinoma of the esophagus is an aggressive and lethal malignancy with an increasing incidence worldwide.Incidence rates vary internationally,with the highest rates found in Southern and Eastern Africa and Eastern Asia,and the lowest in Western and Middle Africa and Central America.Patients with locally advanced disease face a poor prognosis,with 5-year survival rates ranging from 15%-34%.Recent clinical trials have evaluated different strategies for management of locoregional cancer;however,because of stage migration and changes in disease epidemiology,applying these trials to clinical practice has become a daunting task.We searched Medline and conference abstracts for randomized studies published in the last 3 decades.We restricted our search to articles published in English.Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States.Esophagectomy remains an essential component of treatment and can lead to improved overall survival,especially when performed at high volume institutions.The role of adjuvant chemotherapy following curative resection is still unclear.External beam radiation therapy alone is considered palliative and is typically reserved for patients with a poor performance status.

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

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 accuracy.RESULTS 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.

miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases

Recent evidence shows that certain microRNAs （miRNAs） play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown. In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases, miRNA expression was determined using quantitative real-time polymerase chain reaction. Cox proportional hazard models adjusting for age at diagnosis, clinical stage and Gleason score were used to estimate hazard ratios （HR） and 95% confidence intervals （95% CI） for recurrence free survival. A significantly （P=0.014） higher proportion of recurrent cases （78,6%） than non-recurrent cases （48.6%） had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients. Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese （HR=6.15, 95% CI= 1.04-36.48, P=-0.045）, but not in non-obese （HR= 1.28, 95% C1=0.30-5.49, P=0.74） cases. A significant association with recurrence was not observed for the expression of miR-221 and miR-222. In summary, our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases. Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.

Management of borderline resectable pancreatic cancer

Pancreatic cancer is the fourth most common cause of cancer death in the United States. Surgery remains the only curative option; however only 20% of the patients have resectable disease at the time of initialpresentation. The definition of borderline resectable pancreatic cancer is not uniform but generally denotes to regional vessel involvement that makes it unlikely to have negative surgical margins. The accurate staging of pancreatic cancer requires triple phase computed tomography or magnetic resonance imaging of the pancreas. Management of patients with borderline resectable pancreatic cancer remains unclear. The data for treatment of these patients is primarily derived from retrospective single institution experience. The prospective trials have been plagued by small numbers and poor accrual. Neoadjuvant therapy is recommended and typically consists of chemotherapy and radiation therapy. The chemotherapeutic regimens continue to evolve along with type and dose of radiation therapy. Gemcitabine or 5-fluorouracil based chemotherapeutic combinations are administered. The type and dose of radiation vary among different institutions. With neoadjuvant treatment, approximately 50% of the patients are able to undergo surgical resections with negative margins obtained in greater than 80% of the patients. Newer trials are attempting to standardize the definition of borderline resectable pancreatic cancer and treatment regimens. In this review, we outline the definition, imaging requirements and management of patients with borderline resectable pancreatic cancer.

Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer

Pancreatic cancer is a challenging malignancy with limited treatment options and poor life expectancy.The only curative option is surgical resection,but only 15%-20%of patients are resectable at presentation because more than 50%of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer(LAPC).The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation therapy.Recent developments in minimally invasive ablative techniques may add to the treatment armamentarium of LAPC.There are increasing number of studies evaluating these novel ablative techniques,including radiofrequency ablation,microwave ablation,cryoablation and irreversible electroporation.Most studies which included pancreatic tumor ablation,demonstrated improved overall survival in LAPC patients.However,the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment combinations.Patients with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%.The most common metastatic site is the liver as 90%of pancreatic cancer patients develop liver metastasis.Chemotherapy is the primary treatment option for patients with metastatic pancreatic cancer.However,when the tumor is not responding to chemotherapy or severe drug toxicity develops,locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected patients.During the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer patients.These new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these procedures.This review summarizes new ablative options for patients with LAPC and percutaneous liver-directed therapies for patients with liver-dominant metastatic disease.

Poly （ADP-ribose） polymerase inhibitor： an evolving paradigm in the treatment of prostate cancer

Recent phase I studies have reported single-agent activities of poly （ADP-ribose） polymerase （PARP） inhibitor in sporadic and in BRCA-mutant prostate cancers. Two of the most common genetic alterations in prostate cancer, ETS gene rearrangement and loss of PTEN, have been linked to increased sensitivity to PARP inhibitor in preclinical models. Emerging evidence also suggests that PARP1 plays an important role in mediating the transcriptional activities of androgen receptor （AR） and ETS gene rearrangement. In this article, the preclinical work and early-phase clinical trials in developing PARP inhibitor-based therapy as a new treatment paradigm for metastatic prostate cancer are reviewed.

Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model

AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.

Updates in the use of radiotherapy in the management of primary and locally-advanced penile cancer

Objective:Penile cancer is a rare malignancy in most developed countries,but may represent a significant oncologic challenge in certain African,Asian,and South American regions.Various treatment approaches have been described in penile cancer,including radio-therapy.This review aimed to provide a synopsis of radiotherapy use in penile cancer management and the associated toxicities.In addition,we aimed to discuss palliative radiation for metastases to the penis and provide a brief overview of how tumor biology may assist with treatment decision-making.Methods:Peer-reviewed manuscripts related to the treatment of penile cancer with radio-therapy were evaluated by a PubMed search(1960-2021)in order to assess its role in the definitive and adjuvant settings.Selected manuscripts were also evaluated for descriptions of radiation-related toxicity.Results:Though surgical resection of the primary is an excellent option for tumor control,select patients may be treated with organ-sparing radiotherapy by either external beam radiation or brachytherapy.Data from randomized controlled trials comparing radiotherapy and surgery are lacking,and thus management is frequently determined by institutional practice patterns and available expertise.Similarly,this lack of clinical trial data leads to divergence in opinion regarding lymph node management.This is further complicated in that many cited studies evaluating lymph node radiotherapy used non-modern radiotherapy delivery techniques.Groin toxicity from either surgery or radiotherapy remains a challenging problem and further risk assessment is needed to guide intensification with multi-modal therapy.Intrinsic differences in tumor biology,based on human papillomavirus infection,may help aid future prognostic and predictive models in patient risk stratification or treatment approach.Conclusion:Penile cancer is a rare disease with limited clinical trial data driving the majority of treatment decisions.As a result,the goal of management is to effectively treat the disease while balancing the importance of quality of life through integrated multidisciplinary discussions.More international collaborations and interrogations of penile cancer biology are needed to better understand this disease and improve patient outcomes.

Penile cancer:Updates in systemic therapy

Penile cancer is a rare genitourinary malignancy with a greater incidence in parts of Asia,South America,and Africa.Outcomes are very poor in patients with advanced disease and in those who do not respond to frstine mutimodal therapy.Among systemic therapy options,platinum-based chemotherapy is used in the frst line;however,approximately half of patients do not benefit.Response rates to systeric therapy as subsequent line treatment are historically dismal.There is also a paucity of prognostic and predictive tools within the context of penile cancer.As such,there remains an urgent need to expand systemic treatment options for patients with advanced penile cancer.The purpose of this review is to summarize the existing evidence for standard-of-care lines of systemic treatment,examine the potential of novel lines of systemic therapy,and provide an update as to the status of these new therapies within the context of penile cancer.

Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma:a single-institution experience

Extranodal marginal zone lymphoma(EMZL)encompasses 70%of cases of marginal zone lymphoma.Frontline bendamustine and rituximab(BR)were derived from trials involving other indolent non-Hodgkin’s lymphomas.Only one trial has evaluated frontline BR prospectively in EMZL.This retrospective study reports outcomes among EMZL patients receiving frontline BR.Twenty-five patients were included with a median age of 69 years(40–81).Five(20.0%)patients had stage Ⅰ/Ⅱ disease,and 20(80.0%)had stage Ⅲ/Ⅳ disease.The median number of cycles was 6.0(3.0–6.0).Maintenance rituximab was administered to 10(41.7%)individuals.Overall response rate(ORR)was 100.0%(60.0%complete response,40.0%partial response).Medians of overall survival and progression-free survival were not reached.The estimated 2-year progression-free survival was 85.2%and overall survival was 100.0%.Four(16.6%)patients had infections related to treatment;3(12.0%)transformed to diffuse large B-cell lymphoma;5(20.8%)had a relapse or progression of EMZL;and 3(12.0%)died unrelated to BR.BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

滤泡细胞性淋巴瘤转化为c-MYC重排的“双击”或“三击”B细胞淋巴瘤3例及文献复习

目的:本文旨在对"双击"B细胞淋巴瘤(double-hit B-cell lymphoma,DHL)和"三击"B细胞淋巴瘤(triple-hit B-celllymphoma,THL)的诊断及治疗分析,以期提高对该类淋巴瘤的认识,为其诊治提供临床经验。方法:对2011年1月至2012年12月本院收治的3例滤泡细胞性淋巴瘤(follicular lymphoma,FL)转化的"双击"或"三击"B细胞淋巴瘤病例进行分析,3例患者均经免疫组织化学、荧光染色体原位杂交(fluorescence in situ hybridization,FISH)检测诊断明确。结果:1例"三击"患者3个月后死亡,2例经R-CHOP,R-ESHAP等方案化疗仍未达到完全缓解。结论:"双击"淋巴恶性程度高,多伴有中枢神经系统、骨髓等髓外病变,病程呈侵袭性,部分病例由滤泡细胞淋巴瘤转化而来,对化疗不敏感,患者预后差,FISH检测是诊断该病的重要手段,目前尚无标准治疗方案。

未分化多形性肉瘤合并阴茎癌1例

恶性纤维组织细胞瘤（MFH）根据WHO的最新分类被称为未分化多形性肉瘤（undifferentiated pleomorphic sarcoma not otherwise specified），是一种主要由成纤维细胞和多形性细胞组成，多发生于骨与软组织的少见恶性间叶性肿瘤，其骨的发病率约占所有骨原发恶性肿瘤的2％，治疗主要是以手术为主结合放化疗的综合治疗。阴茎癌是一种少见疾病，随着卫生状况的好转，发病率有所下降，约占我国男性恶性肿瘤的1％以下，在美国该病发病率为0．58／100000。本病以鳞状细胞癌为主，主要通过淋巴途径转移，同时可以通过血行转移至肺。治疗包括局部原发癌切除、对转移淋巴结的处理以及放化疗等辅助治疗。我科收治1例未分化多形性肉瘤合并阴茎癌患者，现报告如下。

Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy

BACKGROUND Intraductal papillary mucinous neoplasms(IPMNs)are non-invasive pancreatic precursor lesions that can potentially develop into invasive pancreatic ductal adenocarcinoma.Currently,the International Consensus Guidelines(ICG)for IPMNs provides the basis for evaluating suspected IPMNs on computed tomography(CT)imaging.Despite using the ICG,it remains challenging to accurately predict whether IPMNs harbor high grade or invasive disease which would warrant surgical resection.A supplementary quantitative radiological tool,radiomics,may improve diagnostic accuracy of radiological evaluation of IPMNs.We hypothesized that using CT whole lesion radiomics features in conjunction with the ICG could improve the diagnostic accuracy of predicting IPMN histology.AIM To evaluate whole lesion CT radiomic analysis of IPMNs for predicting malignant histology compared to International Consensus Guidelines.METHODS Fifty-one subjects who had pancreatic surgical resection at our institution with histology demonstrating IPMN and available preoperative CT imaging were included in this retrospective cohort.Whole lesion semi-automated segmentation was performed on each preoperative CT using Healthmyne software(Healthmyne,Madison,WI).Thirty-nine relevant radiomic features were extracted from each lesion on each available contrast phase.Univariate analysis of the 39 radiomics features was performed for each contrast phase and values were compared between malignant and benign IPMN groups using logistic regression.Conventional quantitative and qualitative CT measurements were also compared between groups,viaχ2(categorical)and Mann Whitney U(continuous)variables.RESULTS Twenty-nine subjects(15 males,age 71±9 years)with high grade or invasive tumor histology comprised the"malignant"cohort,while 22 subjects(11 males,age 70±7 years)with low grade tumor histology were included in the"benign"cohort.Radiomic analysis showed 18/39 precontrast,19/39 arterial phase,and 21/39 venous phase features differentiated malignant from benign IPMNs(P<0.05).Multivariate analysis including only ICG criteria yielded two significant variables:thickened and enhancing cyst wall and enhancing mural nodule<5 mm with an AUC(95%CI)of 0.817(0.709-0.926).Multivariable post contrast radiomics achieved an AUC(95%CI)of 0.87(0.767-0.974)for a model including arterial phase radiomics features and 0.834(0.716-0.953)for a model including venous phase radiomics features.Combined multivariable model including conventional variables and arterial phase radiomics features achieved an AUC(95%CI)of 0.93(0.85-1.0)with a 5-fold cross validation AUC of 0.90.CONCLUSION Multi-phase CT radiomics evaluation could play a role in improving predictive capability in diagnosing malignancy in IPMNs.Future larger studies may help determine the clinical significance of our findings.

Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR:A systematic literature review

AIM:To review literature on efficacy and safety of octreotide-long-acting repeatable(LAR)used at doses higher than the Food and Drug Administration(FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors(NETs).METHODS:We searched Pub Med and Cochrane Library from 1998-2012,5 conferences(American Society of Clinical Oncology,Endocrine Society,European Neuroendocrine Tumor Society,European Society for Medical Oncology,North American Neuroendocrine Tumor Society)from 2000-2013 using Me SH and keyterms including neuroendocrine tumors,carcinoid tumor,carcinoma,neuroendocrine,and octreotide.Bibliographies of accepted articles were also searched.Two reviewers reviewed titles,abstracts,and full-length articles.Studies that reported data on efficacy and safety of≥30 mg/mo octreotide-LAR for NETs in human subjects,published in any language were included in the review.RESULTS:The search identified 1086 publications,of which 238 underwent full-text review(20 were translated into English);17 were included in the review.Studies varied in designs,subjects,octreotide-LAR regimens,and definition of outcomes.Eleven studies reported use of higher doses to control symptoms and tumor progression,although symptom severity and formal quality-of-life analysis were not quantitatively measured.Ten studies reported efficacy,describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo.Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression.Eight studies reported safety;there was no evidence of increased toxicity associated with doses of octreotide-LAR>30 mg/mo.CONCLUSION:As reported in this review,octreotide-LAR at doses>30 mg/mo is being prescribed for symptom and tumor control in NET patients.Furthermore,expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.

Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.

Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation:Where do we stand?

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept &#x0201c;ablate and wait&#x0201d; has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of &#x0201c;ablate and wait&#x0201d; in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.

Prognostic value of pre-treatment F-18-FDG PET-CT in patients with hepatocellular carcinoma undergoing radioembolization

AIM To evaluate the value of pre-treatment 18F-FDG PET/CT in patients with HCC following liver radioembolization.METHODS We identified 34 patients with HCC who underwent an FDG PET/CT scan prior to hepatic radioembolization at our institution between 2009 and 2013. Patients wereseen in clinic one month after radioembolization and then at 2-3 mo intervals. We assessed the influence of FDG tumor uptake on outcomes including local liver control(LLC), distant liver control(DLC), time to distant metastases(DM), progression free survival(PFS) and overall survival(OS).RESULTS The majority of patients were males(n = 25, 74%), and had Child Pugh Class A(n = 31, 91%), with a median age of 68 years(46-84 years). FDG-avid disease was found in 19(56%) patients with SUVmax ranging from 3 to 20. Female patients were more likely to have an FDG-avid HCC(P = 0.02). Median follow up of patients following radioembolization was 12 months(1.2-62.8 mo). FDG-avid disease was associated with a decreased 1 year LLC, DLC, DM and PFS(P < 0.05). Using multivariate analysis, FDG avidity predicted for LLC, DLC, and PFS(all P < 0.05).CONCLUSION In this retrospective study, pre-treatment HCC FDGavidity was found to be associated with worse LLC, DLC, and PFS following radioembolization. Larger studies are needed to validate our initial findings to assess the role of F-18-FDG PET/CT scans as biomarker for patients with HCC following radioembolization.

Clinical management of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes

The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.

Preoperative maximal voluntary ventilation,hemoglobin,albumin,lymphocytes and platelets predict postoperative survival in esophageal squamous cell carcinoma

BACKGROUND Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications.Reduced pulmonary function is associated with poor survival in several cancers,but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma(ESCC)is unclear.Nutritional and systemic inflammation parameters are vital to cancer survival,and the combination of these parameters improves the prognostic value.The hemoglobin,albumin,lymphocytes and platelets(HALP)score is a novel prognostic indicator to reflect the nutritional and inflammation status,but the clinical effects of the HALP score combined with maximal voluntary ventilation(MVV),an important parameter of pulmonary function,have not been well studied in ESCC.AIM To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients.METHODS Data form 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed.Preoperative MVV and HALP data were retrieved from medical archives.The HALP score was calculated by the formula:Hemoglobin(g/L)×albumin(g/L)×lymphocytes(/L)/platelets(/L).The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis.The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested.Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival.RESULTS MVV was significantly associated with gender(P<0.001),age at diagnosis(P<0.001),smoking history(P<0.001),drinking history(P<0.001),tumor length(P=0.013),tumor location(P=0.037)and treatment type(P=0.001).The HALP score was notably associated with gender(P<0.001),age at diagnosis(P=0.035),tumor length(P<0.001)and invasion depth(P=0.001).Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival(all P<0.001).Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival(all P<0.001).The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis.Also,low combination of MVV and HALP score was an independent risk factor for poor overall survival(P<0.001).CONCLUSION MVV,HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.

Screening the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34^(cdc2) kinase

Objective: To screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25phosphatase. Methods: The affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used as the cell cycle-specific targets for screening the antimitotic constituents. We tested 9 extracts isolated from the Chinese medicinal herbs and vegetables including the agents currently used in cancer treatment by measuring the inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry.Results: Cdc25A inhibitory activity and antitumor activity are detected in the extracts isolated from three Chinese medicinal herbs Agrimonapilosa; Herba solani lyrati; Galla chinesis. Conclusion: We found three extracts isolated from Chinese medicinal herbs have potential inhibitory activity of Cdc25 phosphatase using a highly specific mechanism-based screen assay for antimitotic drug discovery.