BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemoth...BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.展开更多
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
Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system b...Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.展开更多
Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that d...Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination,pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy,pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology,primary prevention, early detection, and possibly even therapeutic strategies.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
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 m...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.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
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...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.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
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
Triple-negative breast cancer(TNBC)is defined as a type of breast cancer with lack of expression of estrogen receptor,progesterone receptor and human epidermal growth factor 2 protein.In comparison to other types of b...Triple-negative breast cancer(TNBC)is defined as a type of breast cancer with lack of expression of estrogen receptor,progesterone receptor and human epidermal growth factor 2 protein.In comparison to other types of breast cancer,TNBC characterizes for its aggressive behavior,more prone to early recurrence and a disease with poor response to molecular target therapy.Although TNBC is identified in only 25%-30%of American breast cancer cases annually,these tumors continue to be a therapeutic challenge for clinicians for several reasons:Tumor heterogeneity,limited and toxic systemic therapy options,and often resistance to current standard therapy,characterized by progressive disease on treatment,residual tumor after cytotoxic chemotherapy,and early recurrence after complete surgical excision.Cell-surface targeted therapies have been successful for breast cancer in general,however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC.Recently,several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development.The purpose of this work is to review the current clinical challenges posed by TNBC,the therapeutic approaches currently in use,and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.展开更多
Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to addr...Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns,especially fertility.The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors.However,genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel.This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis,particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing.Other hereditary cancers are also addressed;however,less is known about the psychosocial and fertility concerns in these AYA populations.Additionally,we provide an overview of the concept of"oncofertility"-the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients-and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’treatment planning related to reproductive health and fertility.展开更多
Applephenon®, a purified extract prepared from green apples, was examined for its cytotoxicity and inhibitory effects on the proliferation of cultures of normal human keratinocytes and several epidermoid cancer...Applephenon®, a purified extract prepared from green apples, was examined for its cytotoxicity and inhibitory effects on the proliferation of cultures of normal human keratinocytes and several epidermoid cancer cell lines. Our HPLC studies demonstrated a high content of phenolic compounds (>65%), including catechin, epicatechin, caffeic acid and phloretin as well as polyphenols such as proanthocyanidins. Applephenon® demonstrated a greater cytotoxic effect against HeLa, A431 cancer cell lines and HaCaT, an immortalized keratinocyte cell line than serum-free cultures of proliferating normal human keratinocytes (NHK). Proliferation of NHK was inhibited at concentrations above 0.0013% while concentrations above 0.005% were cytotoxic. By contrast, Applephenon® solutions above 0.00025% killed each of the cancer cell lines. Treated cells displayed increased intercellular separation and evidence of keratinizing stratification. We also tested the effect of epicatechin, and two isoflavonoids, genistein and daidzein, on cancer cell lines. Hela cells were more sensitive to epicatechin and genistein inhibition of cell growth and cytotoxicity than were NHK. Daidzein at these concentrations had little effect on cancer cells. These results indicate that Applephenon® and some of its phenolic components have selective anticancer activity.展开更多
Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay...Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC);2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC);3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC);4) the mouse skin papilloma (MPA) assay;and 5) a novel retinoid bioassay in which retinoids display IC<sub>50</sub> values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED<sub>50</sub> values in the HTOC system and reduction in TPA-induced ODC enzyme activity;2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity;and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.展开更多
BACKGROUND Marginal zone lymphoma(MZL)is an indolent non-Hodgkin B cell lymphoma with various architectural pattern including perifollicular,follicular colonization,nodular,micronodular,and diffuse patterns.A scleroti...BACKGROUND Marginal zone lymphoma(MZL)is an indolent non-Hodgkin B cell lymphoma with various architectural pattern including perifollicular,follicular colonization,nodular,micronodular,and diffuse patterns.A sclerotic variant has not been previously reported and represents a diagnostic pitfall.CASE SUMMARY A 66-year-old male developed left upper extremity swelling.Chest computed tomography(CT)in September 2020 showed 14 cm mass in left axilla.Needle core biopsy of axillary lymph node showed sclerotic tissue with atypical B lymphoid infiltrate but was non-diagnostic.Excisional biopsy was performed for diagnosis and showed extensive fibrosis and minor component of infiltrating B cells.Flow cytometry showed a small population of CD5-,CD10-,kappa restricted B cells.Monoclonal immunoglobulin heavy chain and light chain gene rearrangement were identified.Upon being diagnosed with MZL,patient was treated with rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone and achieved complete remission by positron emission tomography/CT.CONCLUSION This is an important case report because by morphology this case could have easily been overlooked as non-specific fibrosis with chronic inflammation representing a significant diagnostic pitfall.Moreover,this constitutes a new architectural pattern.While sclerotic lymphomas have rarely been described(often misdiagnosed as retroperitoneal fibrosis),we do not know of any cases describing this architectural presentation of MZL.展开更多
文摘BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.
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Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.
文摘Ovarian cancer(OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination,pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy,pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology,primary prevention, early detection, and possibly even therapeutic strategies.
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.
文摘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.
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.
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Triple-negative breast cancer(TNBC)is defined as a type of breast cancer with lack of expression of estrogen receptor,progesterone receptor and human epidermal growth factor 2 protein.In comparison to other types of breast cancer,TNBC characterizes for its aggressive behavior,more prone to early recurrence and a disease with poor response to molecular target therapy.Although TNBC is identified in only 25%-30%of American breast cancer cases annually,these tumors continue to be a therapeutic challenge for clinicians for several reasons:Tumor heterogeneity,limited and toxic systemic therapy options,and often resistance to current standard therapy,characterized by progressive disease on treatment,residual tumor after cytotoxic chemotherapy,and early recurrence after complete surgical excision.Cell-surface targeted therapies have been successful for breast cancer in general,however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC.Recently,several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development.The purpose of this work is to review the current clinical challenges posed by TNBC,the therapeutic approaches currently in use,and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.
文摘Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns,especially fertility.The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors.However,genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel.This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis,particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing.Other hereditary cancers are also addressed;however,less is known about the psychosocial and fertility concerns in these AYA populations.Additionally,we provide an overview of the concept of"oncofertility"-the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients-and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’treatment planning related to reproductive health and fertility.
文摘Applephenon®, a purified extract prepared from green apples, was examined for its cytotoxicity and inhibitory effects on the proliferation of cultures of normal human keratinocytes and several epidermoid cancer cell lines. Our HPLC studies demonstrated a high content of phenolic compounds (>65%), including catechin, epicatechin, caffeic acid and phloretin as well as polyphenols such as proanthocyanidins. Applephenon® demonstrated a greater cytotoxic effect against HeLa, A431 cancer cell lines and HaCaT, an immortalized keratinocyte cell line than serum-free cultures of proliferating normal human keratinocytes (NHK). Proliferation of NHK was inhibited at concentrations above 0.0013% while concentrations above 0.005% were cytotoxic. By contrast, Applephenon® solutions above 0.00025% killed each of the cancer cell lines. Treated cells displayed increased intercellular separation and evidence of keratinizing stratification. We also tested the effect of epicatechin, and two isoflavonoids, genistein and daidzein, on cancer cell lines. Hela cells were more sensitive to epicatechin and genistein inhibition of cell growth and cytotoxicity than were NHK. Daidzein at these concentrations had little effect on cancer cells. These results indicate that Applephenon® and some of its phenolic components have selective anticancer activity.
文摘Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC);2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC);3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC);4) the mouse skin papilloma (MPA) assay;and 5) a novel retinoid bioassay in which retinoids display IC<sub>50</sub> values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED<sub>50</sub> values in the HTOC system and reduction in TPA-induced ODC enzyme activity;2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity;and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.
文摘BACKGROUND Marginal zone lymphoma(MZL)is an indolent non-Hodgkin B cell lymphoma with various architectural pattern including perifollicular,follicular colonization,nodular,micronodular,and diffuse patterns.A sclerotic variant has not been previously reported and represents a diagnostic pitfall.CASE SUMMARY A 66-year-old male developed left upper extremity swelling.Chest computed tomography(CT)in September 2020 showed 14 cm mass in left axilla.Needle core biopsy of axillary lymph node showed sclerotic tissue with atypical B lymphoid infiltrate but was non-diagnostic.Excisional biopsy was performed for diagnosis and showed extensive fibrosis and minor component of infiltrating B cells.Flow cytometry showed a small population of CD5-,CD10-,kappa restricted B cells.Monoclonal immunoglobulin heavy chain and light chain gene rearrangement were identified.Upon being diagnosed with MZL,patient was treated with rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone and achieved complete remission by positron emission tomography/CT.CONCLUSION This is an important case report because by morphology this case could have easily been overlooked as non-specific fibrosis with chronic inflammation representing a significant diagnostic pitfall.Moreover,this constitutes a new architectural pattern.While sclerotic lymphomas have rarely been described(often misdiagnosed as retroperitoneal fibrosis),we do not know of any cases describing this architectural presentation of MZL.