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 tria...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.展开更多
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 d...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.展开更多
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 Asi...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.展开更多
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 perfo...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.展开更多
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 initialpresenta...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.展开更多
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 canc...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.展开更多
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 ac...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.展开更多
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 m...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.展开更多
Herpes simplex virus(HSV) is known to cause esophagitis in immunosuppressed patients; however, it is rarely seen in immunocompetent patients. We present a unique case of HSV esophagitis in a healthy male, without any ...Herpes simplex virus(HSV) is known to cause esophagitis in immunosuppressed patients; however, it is rarely seen in immunocompetent patients. We present a unique case of HSV esophagitis in a healthy male, without any immunocompromising conditions or significant comorbidities. The patient presented with a two-week history of dysphagia, odynophagia and epigastric pain. Physical exam revealed oral hyperemia without any visible ulcers or vesicles. He underwent esophagogastroduodenoscopy which noted severe esophagitis with ulceration. Esophageal biopsies were positive for HSV. Serology was positive for HSV as well. After initiating treatment with Famciclovir 250 mg 3 times/d, high dose proton pump inhibitor and sucralfate, patient had complete resolution of symptoms at his 2.5 wk follow up appointment. Subsequent workup did not reveal any underlying immune disorders. While HSV is a known causative of esophagitis in the immunocompromised, its presentation in healthy patients without any significant comorbidity is uncommon. Presentation with a systemic viral prodrome further makes this case unique.展开更多
The long battle with cancer began centuries ago and despite many victories,the overall incidence continues to rise and it sometimes feels like that we are losing the war.The high rates and mortality of cancer have bro...The long battle with cancer began centuries ago and despite many victories,the overall incidence continues to rise and it sometimes feels like that we are losing the war.The high rates and mortality of cancer have brought an increasing burden to society and so defeating the disease remains an urgent and unmet clinical need.In recent years,there has been a profound development of new knowledge and technologies that are widely employed in cancer research across multiple disciplines and even moreso,across the world.In modern times,it is hard to keep up with these breakthroughs,especially when they occur in varying regions.To address this,we are delighted to announce the launch of Malignancy Spectrum(MSP)in a bid to bring global advances in these disciplines together in one place.展开更多
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).M...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.展开更多
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 agen...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.展开更多
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...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.展开更多
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 classif...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.展开更多
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...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.展开更多
AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for p...AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs.展开更多
Human papillomavirus(HPV)related squamous cell carcinoma(SCC)involving the anal canal is a well-known carcinoma associated with high-risk types of HPV.HPVrelated SCC with papillary morphology(papillary SCC)has been de...Human papillomavirus(HPV)related squamous cell carcinoma(SCC)involving the anal canal is a well-known carcinoma associated with high-risk types of HPV.HPVrelated SCC with papillary morphology(papillary SCC)has been described in the oropharynx.We describe,for the first time,a case of anal HPV-related squamous carcinoma with papillary morphology.The tumor arose from the anal mucosa.The biopsies revealed a superficially invasive SCCwith prominent papillary features and associated in situ carcinoma.The tumor cells were positive for p16 and were also positive for high-risk types of HPV using chromogenic in situ hybridization.The findings are consistent with a HPV-related SCC of the anal canal with papillary features.This tumor shows histologic features similar to a papillary HPV-related SCC of the oropharynx.Additional studies are needed to characterize these lesions.展开更多
Plasmablastic lymphoma(PBL) rarely occurs in the gastrointestinal(GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar cas...Plasmablastic lymphoma(PBL) rarely occurs in the gastrointestinal(GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar case reports published in peer-reviewed journals. In our first case, a 40 year-old human immunodeficiency viruspositive male presented with a hemorrhoid-like sensation, and was diagnosed with PBL via biopsy of a rectal mass. The second case involves a 65 year-old healthy male with bloody diarrhea who was found to have PBL in a resected sigmoid mass. The third patient was a 41 year-old male with a history of Crohn's disease who presented with abdominal pain, diarrhea, and weight loss. A small intestinal mass(PBL) was removed. The fourth patient was a 65-year-old male who was found PBL after surgical resection of bowel for his florid Crohn's disease. He later developed secondary acute myeloid leukemia. Clinical outcome was very poor in 3 out of 4 patients as reported in the literature. One patient survived chemotherapy followed by autologous transplant. The prototypical clinical presentation and variations of PBL can help create a more comprehensive differential diagnosis for GI tumors and establish an appropriate therapeutic guideline.展开更多
Breast cancer has long been characterized as a B-cell-related disease with regard to the immune response.For example,data have indicated that B-cell receptor(BCR)recombination read recoveries from breast cancer exome(...Breast cancer has long been characterized as a B-cell-related disease with regard to the immune response.For example,data have indicated that B-cell receptor(BCR)recombination read recoveries from breast cancer exome(WXS)files revealed an increased disease-free survival(DFS)rate.1 However,the antigens stimulating the B-cell response have not been well characterized,particularly via immunogenomics analyses.Thus,we evaluated the net charge per residue(NCPR)for CDR3s,for BCRs expressed on tumor-infiltrating lymphocytes(TILs),to assess its electrostatic complementarity with TP53-mutant amino acids(AAs),because the CDR3 loop domain is the most important part of the BCR polypeptide for antigen-binding specificity.展开更多
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by National Natural Science Foundation of China,No.U1301227,No.81872032 and No.U1804262Doctoral Team Foundation of the First Affiliated Hospital of Zhengzhou University,No.2016-BSTDJJ-03.
文摘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.
基金Supported by National Institutes of Health Grants, No.U56 CA126379 (to Isidro AA and Appleyard CB), No.CA118809 (to Wu J)a National Institutes of Health Predoctoral Fellowship No.F31 GM078951 (to Pagán B)
文摘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.
文摘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.
文摘Herpes simplex virus(HSV) is known to cause esophagitis in immunosuppressed patients; however, it is rarely seen in immunocompetent patients. We present a unique case of HSV esophagitis in a healthy male, without any immunocompromising conditions or significant comorbidities. The patient presented with a two-week history of dysphagia, odynophagia and epigastric pain. Physical exam revealed oral hyperemia without any visible ulcers or vesicles. He underwent esophagogastroduodenoscopy which noted severe esophagitis with ulceration. Esophageal biopsies were positive for HSV. Serology was positive for HSV as well. After initiating treatment with Famciclovir 250 mg 3 times/d, high dose proton pump inhibitor and sucralfate, patient had complete resolution of symptoms at his 2.5 wk follow up appointment. Subsequent workup did not reveal any underlying immune disorders. While HSV is a known causative of esophagitis in the immunocompromised, its presentation in healthy patients without any significant comorbidity is uncommon. Presentation with a systemic viral prodrome further makes this case unique.
文摘The long battle with cancer began centuries ago and despite many victories,the overall incidence continues to rise and it sometimes feels like that we are losing the war.The high rates and mortality of cancer have brought an increasing burden to society and so defeating the disease remains an urgent and unmet clinical need.In recent years,there has been a profound development of new knowledge and technologies that are widely employed in cancer research across multiple disciplines and even moreso,across the world.In modern times,it is hard to keep up with these breakthroughs,especially when they occur in varying regions.To address this,we are delighted to announce the launch of Malignancy Spectrum(MSP)in a bid to bring global advances in these disciplines together in one place.
基金Supported by Novartis Pharmaceuticals Corporation,One Health Plaza,East Hanover,NJ 07936-1080,United States
文摘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.
文摘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.
基金Supported by National Cancer Institute of the National Institutes of Health,No. R37CA229810Biostatistics Core Facility at the H.Lee Moffitt Cancer Center and Research Institute,an NCI designated Comprehensive Cancer Center,No. P30-CA076292
文摘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.
文摘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.
文摘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.
基金Supported by Grants from Novartis Pharmaceuticals Corporation,One Health Plaza,East Hanover,NJ 07936-1080,United States
文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs.
文摘Human papillomavirus(HPV)related squamous cell carcinoma(SCC)involving the anal canal is a well-known carcinoma associated with high-risk types of HPV.HPVrelated SCC with papillary morphology(papillary SCC)has been described in the oropharynx.We describe,for the first time,a case of anal HPV-related squamous carcinoma with papillary morphology.The tumor arose from the anal mucosa.The biopsies revealed a superficially invasive SCCwith prominent papillary features and associated in situ carcinoma.The tumor cells were positive for p16 and were also positive for high-risk types of HPV using chromogenic in situ hybridization.The findings are consistent with a HPV-related SCC of the anal canal with papillary features.This tumor shows histologic features similar to a papillary HPV-related SCC of the oropharynx.Additional studies are needed to characterize these lesions.
文摘Plasmablastic lymphoma(PBL) rarely occurs in the gastrointestinal(GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar case reports published in peer-reviewed journals. In our first case, a 40 year-old human immunodeficiency viruspositive male presented with a hemorrhoid-like sensation, and was diagnosed with PBL via biopsy of a rectal mass. The second case involves a 65 year-old healthy male with bloody diarrhea who was found to have PBL in a resected sigmoid mass. The third patient was a 41 year-old male with a history of Crohn's disease who presented with abdominal pain, diarrhea, and weight loss. A small intestinal mass(PBL) was removed. The fourth patient was a 65-year-old male who was found PBL after surgical resection of bowel for his florid Crohn's disease. He later developed secondary acute myeloid leukemia. Clinical outcome was very poor in 3 out of 4 patients as reported in the literature. One patient survived chemotherapy followed by autologous transplant. The prototypical clinical presentation and variations of PBL can help create a more comprehensive differential diagnosis for GI tumors and establish an appropriate therapeutic guideline.
文摘Breast cancer has long been characterized as a B-cell-related disease with regard to the immune response.For example,data have indicated that B-cell receptor(BCR)recombination read recoveries from breast cancer exome(WXS)files revealed an increased disease-free survival(DFS)rate.1 However,the antigens stimulating the B-cell response have not been well characterized,particularly via immunogenomics analyses.Thus,we evaluated the net charge per residue(NCPR)for CDR3s,for BCRs expressed on tumor-infiltrating lymphocytes(TILs),to assess its electrostatic complementarity with TP53-mutant amino acids(AAs),because the CDR3 loop domain is the most important part of the BCR polypeptide for antigen-binding specificity.