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Cancer Drug Resistance 2023年第3期6卷 642-655页

作者： Arya Mariam Roy Saby George Division of Hematology and Oncology Department of Internal MedicineRoswell Park Comprehensive Cancer CenterBuffaloNY 14203USA

The introduction of immune checkpoint inhibitor (ICI) has revolutionized the treatment of metastatic renal cell carcinoma (mRCC) and has dramatically improved the outcomes of patients. The use of monotherapy or combinations of ICIs targeting PD-1/PD-L1 and CTLA-4, as well as the addition of ICIs with tyrosine kinase inhibitors, has significantly enhanced the overall survival of mRCC patients. Despite these promising results, there remains a subset of patients who either do not respond to treatment (primary resistance) or develop resistance to therapy over time (acquired resistance). Understanding the mechanisms underlying the development of resistance to ICI treatment is crucial in the management of mRCC, as they can be used to identify new targets for innovative therapeutic strategies. Currently, there is an unmet need to develop new predictive and prognostic biomarkers that can aid in the development of personalized treatment options for mRCC patients. In this review, we summarize several mechanisms of ICI resistance in RCC, including alterations in tumor microenvironment, upregulation of alternative immune checkpoint pathways, and genetic and epigenetic changes. Additionally, we highlight potential strategies that can be used to overcome resistance, such as combination therapy, targeted therapy, and immune modulation.

关键词： Renal cell carcinoma immunotherapy immune checkpoint inhibitors primary resistance acquired resistance immune exhaustion markers immunosuppressive tumor microenvironment

Advances in percutaneous stone surgery

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Asian Journal of Urology 2015年第1期2卷 26-32页

作者： Christopher Hartman Nikhil Gupta David Leavitt David Hoenig Zeph Okeke Arthur Smith Hofstra North Shore-LIJ School of Medicine The Arthur Smith Institute for UrologyNew Hyde ParkNYUSA

Treatment of large renal stones has changed considerably in recent *** increasing prevalence of nephrolithiasis has mandated that urologists perform more surgeries for large renal calculi than before,and this has been met with improvements in percutaneous stone *** this review paper,we examine recent developments in percutaneous stone surgery,including advances in diagnosis and preoperative planning,renal access,patient position,tract dilation,nephroscopes,lithotripsy,exit strategies,and post-operative antibiotic prophylaxis.

关键词： Nephrolithiasis Kidney calculi Percutaneous nephrolithotomy

Monitoring photodynamic therapy of head and neck malignancies with optical spectroscopies

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World Journal of Clinical Cases 2013年第3期1卷 96-105页

作者： Ulas Sunar Department of Cell Stress Biology and Oncology PDT CenterRoswell Park Cancer InstituteBuffaloNew YorkNY 14263United States

In recent years there has been significant developments in photosensitizers(PSs), light sources and light delivery systems that have allowed decreasing the treatment time and skin phototoxicity resulting in more frequent use of photodynamic therapy(PDT) in the clinical settings. Compared to standard treatment approaches such as chemo-radiation and surgery, PDT has much reduced morbidity for head and neck malignancies and is becoming an alternative treatment option. It can be used as an adjunct therapy to other treatment modalities without any additive cumulative side effects. Surface illumination can be an option for pre-malignant and early-stage malignancies while interstitial treatment is for debulking of thick tumors in the head and neck region. PDT can achieve equivalent or greater efficacy in treating head and neck malignancies, suggesting that it may be considered as a first line therapy in the future. Despite progressive development, clinical PDT needs improvement in several topics for wider acceptance including standardization of protocols that involve the same administrated light and PS doses and establishing quantitative tools for PDT dosimetry planning and response monitoring. Quantitative measures such as optical parameters, PS concentration, tissueoxygenation and blood flow are essential for accurate PDT dosimetry as well as PDT response monitoring and assessing therapy outcome. Unlike conventional imaging modalities like magnetic resonance imaging, novel optical imaging techniques can quantify PDT-related parameters without any contrast agent administration and enable real-time assessment during PDT for providing fast feedback to clinicians. Ongoing developments in optical imaging offer the promise of optimization of PDT protocols with improved outcomes.

关键词： Head and neck cancer Photodynamic therapy Monitoring and predicting response Blood flow Oxygenation Oxygen metabolism Diffuse optical imaging

Correlating the interplanetary factors to distinguish extreme and major geomagnetic storms

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Earth and Planetary Physics 2021年第2期5卷 180-186页

作者： Ragini Balachandran Li-Jen Chen Shan Wang Mei-Ching Fok Cornell University IthacaNY 14853USA NASA Goddard Space Flight Center GreenbeltMD 20770USA Department of Astronomy University of MarylandCollege ParkMD 20742USA

We investigate the correlation between Disturbance Storm Time(Dst)characteristics and solar wind conditions for the main phase of geomagnetic storms,seeking possible factors that distinguish extreme storms(minimum Dst<−250 nT)and major storms(minimum Dst<−100 nT).In our analysis of 170 storms,there is a marked correlation between the average rate of change of Dst during a storm’s main phase(ΔDst/Δt)and the storm’s minimum Dst,indicating a fasterΔDst/Δt as storm intensity *** events add a new regime toΔDst/Δt,the hourly time derivative of Dst(dDst/dt),and sustained periods of large amplitudes for southward interplanetary magnetic field Bz and solar wind convection electric field *** find that Ey is a less efficient driver of dDst/dt for extreme storms compared to major storms,even after incorporating the effects of solar wind pressure and ring current *** minimum Dst is correlated with minimum Bz,we observe a similar divergence,with extreme storms tending to have more negative Dst than the trend predicted on the basis of major *** results enable further improvements in existing models for storm predictions,including extreme events,based on interplanetary measurements.

关键词： extreme geomagnetic storm Dst prediction solar wind driving major storms

Preoperative nuclear stress testing in the very old patient population

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World Journal of Cardiology 2020年第5期12卷 210-219页

作者： Amgad N Makaryus John N Makaryus Joseph A Diamond Department of Cardiology Northwell HealthNew Hyde ParkNY11042United States Department of Cardiology Nassau University Medical CenterEast MeadowNY 11554United States

BACKGROUND Elderly patients awaiting moderate to high-risk surgery may undergo nuclear stress testing(NST)in order to evaluate their cardiovascular *** prognostic utility of such testing in the very elderly(≥85 years)has yet to be fully *** and nonogenarians frequently have a number of concurrent conditions including a high rate of coronary disease,and therefore the prognostic value of NST for their preoperative risk assessment has been *** evaluation assesses the ability of nuclear stress testing to predict peri-operative cardiac outcomes in this patient *** To investigate the ability of NST to predict peri-operative cardiac outcomes in elderly patients awaiting moderate to high-risk *** Patients≥85 years undergoing pre-operative NST were retrospectively *** undergoing low-risk surgery were *** adverse cardiac events(MACE)were considered any adverse event that occurred prior to discharge and included acute heart failure,arrhythmia,acute myocardial infarction,unstable angina,or *** between patient risk factors,MACE,and the obtained results of the pre-operative stress testing,ejection fraction(0)were *** A total of 69 patients(mean age 88±2.6 years,31 males)underwent nuclear stress testing prior to *** were 41(60%)patients found to have an abnormal ***(23%)patients were noted to experience post-operative *** significant associations between risk factors and MACE were *** with an abnormal NST and/or a summed stress score≥9 weresignificantly(P<0.01)more likely to develop peri-operative *** Indicated preoperative NST is useful to assess pre-operative risk in elderly patients≥85 years undergoing moderate to high-risk surgery.

关键词： Pharmacologic nuclear stress testing Prognosis Elderly Preoperative assessment Outcomes

Effect of ionization of drug on drug solubilization in SMEDDS prepared using Capmul MCM and caprylic acid

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Asian Journal of Pharmaceutical Sciences 2017年第1期12卷 73-82页

作者： Suhua Li Parshotam Madan Senshang Lin School of Pharmacy Fairleigh Dickinson UniversityFlorham ParkNJ 07932USA College of Pharmacy and Health Sciences St.John’s UniversityQueensNYUSA

The purpose of this study was to investigate the effect of ionization of drug on drug solubilization in SMEDDS(self-microemulsifying drug delivery system) prepared using Capmul MCM and caprylic acid. Solubilization capacity of blank SMEDDS dispersions for danazol,indomethacin and haloperidol as model drugs was determined. Based on the outcomes of solubilization capacity study, drug-loaded SMEDDS formulations were prepared and subjected to dispersion/precipitation study and droplet size analysis. Blank SMEDDS dispersions exhibited the highest solubilization capacity for haloperidol followed by indomethacin and danazol. Furthermore, the solubilization of the three drugs in blank SMEDDS dispersions was explained by a modified mathematical model. Dispersion/precipitation studies indicate that drug-loaded SMEDDS formulations exhibited superiority in solubilizing the drugs in comparison to their respective drug powder. In addition, indomethacin and haloperidol were found to reduce the droplet size of the microemulsions while danazol did not affect droplet size formation for drug-loaded SMEDDS formulations. These findings suggest that ionization of drug affects drug solubilization, droplet size formation, drug loading and drug dispersion/precipitation profiles for the SMEDDS formulations.

关键词： SMEDDS Capmul MCM Caprylic acid Ionization Indomethacin Haloperidol

Role of thermal ablation in the management of colorectal liver metastasis

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Hepatobiliary Surgery and Nutrition 2020年第1期9卷 49-58页

作者： Hideo Takahashi Eren Berber Department of Surgical Oncology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Endocrine Surgery Cleveland ClinicClevelandOHUSA

With a recent randomized prospective trial revealing that thermal ablative therapy as local tumor control improved overall survival (OS) in patients with unresectable colorectal cancer liver metastases (CRLM), thermal ablation continues to remain as an important treatment option in this patient population. Our aim of this article is to review the current role of the ablative therapy in the management of CRLM patients. Main indications for thermal ablation include (Ⅰ) unresectable liver lesions;(Ⅱ) in combination with hepatectomy;(Ⅲ) in patients with significant medical comorbidities or poor performance status (PS);(Ⅳ) a small (<3 cm) solitary lesion, which would otherwise necessitate a major liver resection;and (Ⅴ) patient preference. There are several approaches and modalities for ablative therapy, including open, percutaneous, and laparoscopic approaches, as well as radiofrequency ablation (RFA) and microwave ablation (MWA). Each approach and ablation modality have its own pros and cons. Percutaneous and laparoscopic approaches are preferred due to minimally invasive nature, yet laparoscopic approach has more benefits from thorough intraoperative ultrasound (US) exam as well as complete peritoneal staging with laparoscopy. Similarly, whereas high local tumor failure rate has been a major concern with RFA, MWA or microwave thermosphere ablation (MTA) have demonstrated significantly improved local tumor control due to homogenous tissue heating, ability to reach higher tissue temperatures, and less susceptible to the "heat-sink" effect. Although liver resection is the standard of care for CRLM, there have been some retrospective studies demonstrating similar oncological outcome between ablative therapy and surgical resection in very selected populations with small (<3 cm) solitary CRLM. Lastly, ablative therapy and liver resection should not be mutually exclusive, especially in the management of bilobar liver metastases. Concomitant ablative therapy with hepatectomy

关键词： Thermal ablation radiofrequency ablation (RFA) microwave ablation (MWA) colorectal cancer livermetastasis (CRLM)

Management of Barrett’s esophagus with dysplasia refractory to radiofrequency ablation

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World Journal of Gastroenterology 2020年第17期26卷 2030-2039页

作者： Kara L Raphael Arvind J Trindade Division of Gastroenterology Long Island Jewish Medical CenterZucker School of Medicine at Hofstra/NorthwellNorthwell Health SystemNew Hyde ParkNY 11040United States

Radiofrequency ablation(RFA)is very effective for eradication of flat Barrett’s mucosa in dysplastic Barrett’s esophagus after endoscopic resection of raised ***,in a minority of the time,RFA may be ineffective at eradication of the Barrett’s *** complete eradication of intestinal metaplasia can be challenging in these *** review article focuses on the management of patients with dysplastic Barrett’s esophagus refractory to RFA *** strategies discussed in this review include optimizing the RFA procedure,optimizing acid suppression(with medical,endoscopic,and surgical management),cryotherapy,hybrid argon plasma coagulation,and EndoRotor resection.

关键词： Low-grade dysplasia High-grade dysplasia Radiofrequency ablation Cryotherapy EndoRotor Hybrid argon plasma coagulation Argon plasma coagulation

Endoscopic ultrasound fine needle aspiration vs fine needle biopsy for pancreatic masses,subepithelial lesions,and lymph nodes

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World Journal of Gastroenterology 2021年第26期27卷 4194-4207页

作者： Irving Levine Arvind J Trindade Division of Gastroenterology Long Island Jewish Medical CenterZucker School of Medicine at Hofstra/NorthwellNorthwell Health SystemNew Hyde ParkNY 11040United States

Endoscopic ultrasound tissue acquisition,in the form of both fine needle aspiration(EUS-FNA)and fine needle biopsy(EUS-FNB),is utilized for pancreatic mass lesions,subepithelial lesions,and lymph node *** procedures are safe and yield high diagnostic *** its high diagnostic yield,EUS-FNA has potential limitations associated with cytological aspirations,including inability to determine histologic architecture,and a small quantitative sample for further immunohistochemical ***-FNB,with its larger core biopsy needle,was designed to overcome these potential ***,it remains unclear which technique should be used and for which *** trials are plagued by heterogeneity at every stage of comparison;including variable needles used,and different definitions of endpoints,which therefore limit ***,we present a review of prospective trials,systematic reviews,and meta-analyses on studies examining EUS-FNA vs *** comparative trials of EUS-FNA vs EUS-FNB primarily focus on pancreatic mass lesions,and yield conflicting results in terms of demonstrating the superiority of one ***,consistent among trials is the potential for diagnosis with fewer passes,and a larger quantity of sample achieved for next generation *** regard to subepithelial lesions and lymph node biopsy,fewer prospective trials exist,and larger prospective studies are *** on the available literature,we would recommend EUS-FNB for peri-hepatic lymph nodes.

关键词： Endoscopic ultrasound fine needle aspiration Endoscopic ultrasound fine needle biopsy Pancreatic lesions Subepithelial lesions Lymph node biopsy

Endoscopic lysis of bladder scar associated with Hunner’s lesions:A new technique

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Asian Journal of Urology 2015年第1期2卷 59-62页

作者： Sonia Bahlani Robert Moldwin The Smith Institute for Urology North Shore-Long Island Jewish Health SystemNew Hyde ParkNYUSA

Objective:Five to ten percent of interstitial cystitis/bladder pain syndrome(IC/BPS)patients have Hunner’s lesions(HL),areas of non-specific inflammation and *** poor quality of life of patients with HL is entwined in associated pain and loss of bladder *** the decrease in bladder capacity is usually dependent on pain,it may also be dependent upon scarring and associated compliance changes produced by the inflammatory *** report reviews the potential role of endoscopic scar lysis using the holmium laser in the management of these patients whose only other therapeutic option is urinary ***:Two patients with HL and“end stage”bladders who underwent holmium laser division of bladder wall scar/tethering were *** data were reviewed with emphasis on safety and ***:Both patients selected for this procedure underwent holmium laser lysis of known scar tissue in an effort to increase bladder capacity and improve symptoms of urinary frequency and pain with bladder *** median age of patients who underwent the procedure was 63(59-67)*** were made with the holmium laser at frequencies of 3e10 Hz of 300e700 J along the region of *** procedures were performed by the same *** was an increase in bladder capacity by 58.3%(50.0%-66.7%).During a mean follow-up of 4.2 years,there appeared to be a significant improvement with an increase in interval time between voids and a decrease in pain with bladder ***:Patients with IC/BPS may be severely debilitated by a clinically significant decrease in their bladder capacity,especially in the face of *** use of the holmium laser to incise regions of scar and bladder wall tethering may produce a clinically significant and durable increase in bladder *** use of this technique as a means of treating bladder scarring poses an excellent adjunct to existing treatment strategies.

关键词： Hunner’s lesions Bladder scar Endoscopic lysis