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lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms:a narrative review and discussion of conceptual similarities in tumor progression and recurrence

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Journal of Pancreatology 2022年第1期5卷 36-40页

作者： Georgios Antonios Margonis Nikolaos Andreatos Jane Wang Matthew J.Weiss christopher l.wolfgang Department of Surgery Memorial Sloan Kettering Cancer CenterNew YorkNY Department of Internal Medicine and Taussig Cancer Institute Cleveland ClinicClevelandOH Department of Surgery University of California San FranciscoSan FranciscoCA Department of Surgery Northwell Health Cancer Institute and Zucker School of Medicine at HofstraL ake Success Department of Surgery NYU Grossman School of MedicineNew YorkNYUSA

Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ( "field defect" ) in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect" may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression;thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.

关键词： Field defect Hepatocellular carcinoma Intraductal papillary mucinous neoplasm Progression Recurrence

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Impact and clinical usefulness of genetic data in the surgical management of colorectal cancer liver metastasis: a narrative review

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Hepatobiliary Surgery and Nutrition 2020年第6期9卷 705-716页

作者： Georgios Antonios Margonis Martin E.Kreis Jaeyun Jane Wang Carsten Kamphues christopher l.wolfgang Matthew J.Weiss Department of Surgery Johns Hopkins University School of MedicineBaltimoreMDUSA Department of General Visceral and Vascular SurgeryCharite Campus Benjamin FranklinBerlinGermany Department of Surgery Northwell Health Cancer Institute and Zucker School of MedicineLake SuccessNYUSA

Importance:In patients who undergo surgery for colorectal cancer liver metastases(CRlM),a number of somatic mutations have been associated with worse overall(OS)and recurrence-free survival(RFS).Although useful,an association with prognosis does not necessarily equate to an impact on surgical management.Objective:The aim of this review was to investigate whether the best-studied somatic mutations impact surgical management of CRlM by informing:(I)post-hepatectomy surveillance;(II)selection of surgical technique;(III)selection of optimal margin width;and(IV)selection of patients for surgery.lastly,we discuss the refinement of genetic data from overall mutation status to specific variants,as well as lesser studied somatic mutations.Evidence Review:We conducted a computerized search using PubMed and Google Scholar for reports published so far,using mesh headings and keywords related to genetic data and CRlM.Findings:Genetic data may impact surgical management of CRlM in three ways.Firstly,KRAS mutations can predict lung recurrences.Secondly,KRAS mutations may help tailor margin width.Thirdly,KRAS mutations may help tailor surgical technique.Conclusions:Although genetic data may impact post-hepatectomy surveillance,selection of surgical technique and optimal margin width,their use to guide surgical selection remains elusive,as the data cannot support denying surgery to patients according to their somatic mutation profile.

关键词： Somatic mutations KRAS BRAF P53 SMAD-4 PIK3CA colorectal liver metastases

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Pancreatic cancer surgery: past, present, and future

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Chinese Journal of Cancer Research 2015年第4期27卷 332-332页

作者： James F.Griffin Katherine E.Poruk christopher l.wolfgang Department of Surgery The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine

The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19 th century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the postoperative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy（PD）, was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20^th century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.

关键词： Whipple pancreaticoduodenectomy（PD） pancreatic cancer pancreatic ductal adenocarcinoma（PDAC） surgical history history of pancreatic cancer Codivilla Kausch William Halsted John Cameron

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Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells

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Cancer Biology & Medicine 2021年第1期18卷 206-214页

作者： Arsen Osipov Alex B.Blair Juliane liberto Jianxin Wang Keyu li Brian Herbst Yao Xu Shiqi li Nan Niu Rufiaat Rashid Ding Ding Yanan liu Zaiqi Wang christopher l.wolfgang Richard A.Burkhart Daniel laheru lei Zheng The Sydney Kimmel Comprehensive Cancer Center Johns Hopkins University School of MedicineBaltimore 21287MDUSA The Pancreatic Cancer Precision Medicine Center of Excellence Program Johns Hopkins University School of MedicineBaltimore 21287MDUSA Department of Oncology Johns Hopkins University School of MedicineBaltimore 21287MDUSA Department of Surgery Johns Hopkins University School of MedicineBaltimore 21287MDUSA Inx Med Shanghai Shanghai 201202China

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(Pltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(Plusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.

关键词： Focal adhesion protein-tyrosine kinases radiotherapy pancreatic neoplasms immunomodulation

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Clinicopathological features and surgical outcomes of resected functional pancreatic neuroendocrine tumors: a single institution experience

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Journal of Pancreatology 2019年第2期2卷 29-34页

作者： Ammar A.Javed Alina Hasanain Aleezay Haider George Jones Zunaira N.Javed Kevin Soares Richard A.Burkhart John l.Cameron Matthew J.Weiss christopher l.wolfgang Jin He Department of Surgery The Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Background:Functional pancreatic neuroendocrine tumors(f-PanNETs)are rare tumors of the pancreas that are associated with excess hormone production.A majority of literature available on these tumors is limited to case reports and small series and discusses a particular subtype.Here,we report the clinicopathological features and outcomes of all f-PanNETs from a high-volume pancreatectomy center.Methods:A prospectively maintained database was used to identify patients who underwent resection for f-PanNETs between January 1995 and December 2015.Patients were stratified by the type of f-PanNET,and their clinicopathological features and outcomes were analyzed and reported.Results:We identified 69 patients with a mean age of 52±16 years,and the majority were female(62%).The most common type of f-PanNET were insulinomas(70%)followed by gastrinomas(15%),and vasoactive intestinal peptidomas(VIPomas)(10%).There was considerable heterogeneity in the presenting symptoms.Patients with insulinomas presented with smaller tumors compared to the other subtypes.Nodal disease was most frequent in patients with VIPomas(71%),and gastrinomas(50%).The median overall survival(OS)was 7.4 years.Elevated Ki-67 and age>65 years were associated with poorer OS.Recurrence was observed in 8 patients(12%)and was most frequent in patients with VIPomas.Recurrence was associated with a poorer OS(P=.012).Conclusion:f-PanNETs are exceedingly rare and present with a wide variety of symptoms,histopathological findings,and outcomes.Surgical resection can help achieve good long-term survival.

关键词： Functional tumor Outcome Pancreatic neuroendocrine tumor

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International expert consensus on laparoscopic pancreaticoduodenectomy

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 464-483页

作者： Renyi Qin Michael l.Kendrick christopher l.wolfgang Barish H.Edil Chinnusamy Palanivelu Rowan WParks Yinmo Yang Jin He Taiping Zhang Yiping Mou Xianjun Yu Bing Peng Palanisamy Senthilnathan Ho-Seong Han Jae Hoon lee Michiaki Unno Steven WMOlde Damink Virinder Kumar Bansal Pierce Chow Tan To Cheung Nim Choi Yu-Wen Tien Chengfeng Wang Manson Fok Xiujun Cai Shengquan Zou Shuyou Peng Yupei Zhao Department of Biliary-Pancreatic Surgery Affiliated Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Mayo Clinic RochesterMNUSA Division of Surgical Oncology Department of SurgeryThe John Hopkins University School of MedicineBaltimoreMDUSA Department of Surgery University of OklahomaOklahoma CityOKUSA Department of Surgical Gastroenterology and Hepatopancreatobiliary Surgery GEM Hospital and Research CentreCoimbatoreTamil NaduIndia Clinical Surgery Royal Infirmary of Edinburgh and University of EdinburghEdinburghUK Department of General Surgery Peking University First HospitalBeijingChina Department of Surgery Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Gastroenterology and Pancreatic Surgery Zhejiang Provincial People’s HospitalHangzhou Medical CollegeHangzhouChina Department of Pancreatic Surgery Fudan University Shanghai Cancer CenterFudan UniversityShanghaiChina Department of Pancreatic Surgery West China HospitalSichuan UniversityChengduChina Department of Surgery Seoul National University College of MedicineSeoul National University Bundang HospitalSeoulKorea Division of Hepatopancreatobiliary Surgery Department of SurgeryAsan Medical CenterSeoulKorea Department of Surgery Tohoku University Graduate School of MedicineSendaiJapan Department of Surgery NUTRIM School of Nutrition and Translational Research in MetabolismMaastricht University Medical CentreMaastrichtThe Netherlands Department of Surgical Disciplines All India Institute of Medical SciencesNew DelhiIndia Department of Hepatopancreatobiliary and Transplant Surgery Singapore General HospitalSingaporeSingapore Department of Surgery The University of Hong KongQueen Mary HospitalHong KongChina Department of General Surgery Hospital Conde S.JanuárioMacaoChina Department of Surgery National Ta

Importance:While laparoscopic pancreaticoduodenectomy(lPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for lPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of lPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on lPD has produced a set of clinical practice statements for the safe development and progression of lP

关键词： Consensus pancreaticoduodenectomy laparoscopy Delphi technique

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IgE-Mast cell mediated allergy: a sensor of food quality

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Signal Transduction and Targeted Therapy 2024年第1期9卷 8-9页

作者： christopher C.Udoye Rudolf A.Manz Institute for Systemic Inflammation Research University of LübeckLübeckGermany

In two recent studies published in Nature,Florsheim et al.and Plum et al.reported that allergic-specific reactions induced by immunoglobulin(Ig)E mediated mast cell activation is crucial for the timely induction of antigen-avoidance behaviour.1,2 These studies prove the concept that allergic sensitization triggers the formation of avoidance behaviour and define the underlying molecular mechanism.

关键词： allergic mechanism

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How to establish an endoscopic bariatric practice

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World Journal of Gastrointestinal Endoscopy 2024年第4期16卷 178-186页

作者： Daniel B Maselli lauren l Donnangelo Brian Coan christopher E McGowan Clinical Research True You Weight LossAtlantaGA 30342United States Clinical Research True You Weight LossCaryNC 27513United States

Obesity is a chronic,progressive,and relapsing disease of excess adiposity that contributes to more than two hundred medical conditions and is projected to affect more than half the adult population of the United States by the year 2030.Given the limited penetrance of traditional bariatric surgery,as well as the cost and adherence barriers to anti-obesity medications,there is growing interest in the rapidly evolving field of endoscopic bariatric therapies(EBTs).EBTs are minimally invasive,same-day,per-oral endoscopic procedures and include endoscopic sleeve gastroplasty,intragastric balloons,and endoscopic bariatric revisional procedures.This field represents an exciting and innovative subspe-cialty within gastroenterology.However,building a successful endoscopic bariatric practice requires intentional,coordinated,and sustained efforts to overcome the numerous obstacles to entry.Common barriers include acquisition of the technical and cognitive skillset,practice limitations including the availability of nutrition counseling,facility capabilities,direct-to-consumer marketing,and financial pressures such as facility and anesthesia fees.As the highest-volume center for metabolic and bariatric endoscopy in the United States,we provide insights into successfully establishing an endoscopic bariatric program.

关键词： Obesity Endoscopic bariatric therapies Bariatric endoscopy Endoscopic sleeve gastroplasty Intragastric balloon Practice management

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Are there sex-based disparities in cataract surgery?

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 137-143页

作者： Matthew D.Geiger Anne M.lynch Alan G.Palestine Nathan C.Grove Karen l.christopher Richard S.Davidson Michael J.Taravella Naresh Mandava Jennifer l.Patnaik Department of Ophthalmology University of Colorado School of MedicineAuroraCO 80045USA

AIM:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract surgery.METHODS:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of Medicine.Data collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BCVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the study.RESUlTS:A total of 11977 eyes from 7253 patients were included in the study.Ocular comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).Conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for confounders.Males had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer significant.Males were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%CI=0.7-0.9,P=0.0005).The BCVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/25.CONClUSION:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for males.However,observed surgical complication rates exhibit almost no difference by sex afte

关键词： cataract surgery sex-based disparity phacoemulsification outcomes

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Graphene-calcium carbonate coating to improve the degradation resistance and mechanical integrity of a biodegradable implant

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Journal of Magnesium and Alloys 2024年第1期12卷 394-404页

作者： lokesh Choudhary Parama Chakraborty Banerjee R.K.Singh Raman Derrek E.lobo christopher D.Easton Mainak Majumder Frank Witte Jörg F.löffler Department of Mechanical and Aerospace Engineering Monash UniversityClayton CampusMelbourneVIC 3800Australia Department of Chemical and Biological Engineering Monash UniversityClayton CampusMelbourneVIC 3800Australia Nanoscale Science and Engineering laboratory(NSEl) Bldg 37Monash UniversityClayton CampusMelbourneVIC 3800Australia CSIRO Materials Science and Engineering Bayview AvenueClaytonVIC 3168Australia Julius Wolff Institute and Berlin Brandenburg Center for Regenerative Therapies Charité–Universitätsmedizin BerlinAugustenburger Platz 113353 BerlinGermany laboratory of Metal Physics and Technology Department of MaterialsETH Zurich8093 ZurichSwitzerland

Biodegradable implants are critical for regenerative orthopaedic procedures,but they may suffer from too fast corrosion in human-body environment.This necessitates the synthesis of a suitable coating that may improve the corrosion resistance of these implants without compromising their mechanical integrity.In this study,an AZ91 magnesium alloy,as a representative for a biodegradable Mg implant material,was modified with a thin reduced graphene oxide(RGO)-calcium carbonate(CaCO_(3))composite coating.Detailed analytical and in-vitro electrochemical characterization reveals that this coating significantly improves the corrosion resistance and mechanical integrity,and thus has the potential to greatly extend the related application field.

关键词： Graphene coating Biodegradable implant Hydroxyapatite Corrosion Magnesium alloy

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