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Pancreatic adenocarcinoma with early esophageal metastasis: A case report and review of literature

World Journal of Clinical Oncology 2020年第2期11卷 83-90页

作者： Ethan Alexander Burns Saro Kasparian Usman Khan Maen Abdelrahim Department of Internal Medicine Houston Methodist HospitalHoustonTX 77030United States Department of Oncology Houston Methodist Cancer CenterHoustonTX 77030United States

BACKGROUND Pancreatic adenocarcinoma is an aggressive malignancy with a high propensity to metastasize.Esophageal metastasis manifesting as dysphagia is rarely reported in the literature and has not to our knowledge been reported prior to the appearance of the primary disease.CASE SUMMARY A patient presented with progressive dysphagia to solids and a persistent earache.Computed tomography of the neck and chest revealed a 3.0 cm×1.8 cm heterogeneous mass originating from the upper third of the esophagus,necrotic cervical and supraclavicular lymphadenopathy,and bilateral pulmonary nodules.She underwent a core needle biopsy of a right cervical node,which suggested a well-differentiated adenocarcinoma of unknown primary.She had an upper endoscopy with biopsy of the esophageal mass suggestive of a welldifferentiated adenocarcinoma.Positron emission tomography imaging revealed increased uptake in the esophageal mass,cervical,and mediastinal lymph nodes.She was started on folinic acid,fluorouracil,and oxaliplatin.Prior to initiation of cycle 8,the patient was found to have a pancreatic body mass that was not present on prior radiographic imaging,confirmed by endoscopic ultrasonography and biopsy to be pancreatic adenocarcinoma.CA19-9 was>10000 U/m L,suggesting a primary pancreaticobiliary origin.CONCLUSION Esophageal metastasis diagnosed before primary pancreatic adenocarcinoma is rare.This case highlights the profound metastatic potential of pancreatic adenocarcinoma.

关键词： Pancreatic body neoplasm Adenocarcinoma Esophagus Metastasis Dysphagia Earache Carcinogenesis Case report

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Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer

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World Journal of Gastroenterology 2021年第38期27卷 6387-6398页

作者： Stephen Safe Rupesh Shrestha Kumaravel Mohankumar Marcell Howard Erik Hedrick Maen Abdelrahim Department of Veterinary Physiology and Pharmacology Texas A&M UniversityCollege StationTX 77845United States Department of Biochemistry and Biophysics Texas A&M UniversityCollege StationTX 77845United States Cancer Institute Cleveland ClinicClevelandOH 44195United States Department of Medical Oncology Houston Methodist Hospital Cancer CenterHoustonTX 77030United States

Specificity protein(Sp)transcription factors(TFs)Sp1,Sp3 and Sp4,and the orphan nuclear receptor 4A1(NR4A1)are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patient survival.Results of knockdown and overexpression of Sp1,Sp3 and Sp4 in pancreatic and other cancer lines show that these TFs are individually pro-oncogenic factors and loss of one Sp TF is not compensated by other members.NR4A1 is also a prooncogenic factor and both NR4A1 and Sp TFs exhibit similar functions in pancreatic cancer cells and regulate cell growth,survival,migration and invasion.There is also evidence that Sp TFs and NR4A1 regulate some of the same genes including survivin,epidermal growth factor receptor,PAX3-FOXO1,α5-andα6-integrins,β1-,β3-andβ4-integrins;this is due to NR4A1 acting as a cofactor and mediating NR4A1/Sp1/4-regulated gene expression through GC-rich gene promoter sites.Several studies show that drugs targeting Sp downregulation or NR4A1 antagonists are highly effective inhibitors of Sp/NR4A1-regulated pathways and genes in pancreatic and other cancer cells,and the triterpenoid celastrol is a novel dual-acting agent that targets both Sp TFs and NR4A1.

关键词： Specificity protein Nuclear receptor 4A1 Pancreatic cancer Transcription factors Ligand inhibitors Nuclear receptor 4A antagonists

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Pancreatic head vs pancreatic body/tail cancer:Are they different?

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 716-723页

作者： Kai Sun Charisma Mylavarapu Aubrey Crenshaw Yuqi Zhang Enshuo Hsu Jiaqiong Xu Marilyn Niravath Stephen L Jones Adriana Ordonez Maen Abdelrahim Houston Methodist Cancer Center Houston Methodist HospitalHoustonTX 77030United States Department of Internal Medicine Houston Methodist HospitalHoustonTX 77030United States Center for Outcomes Research Houston Methodist Research InstituteHoustonTX 77030United States

BACKGROUND The impact of pancreatic tumor location on patient survival has been studied in large national data-based analyses which yielded controversial results.AIM To explore if pancreatic head cancer(PHC)and pancreatic body/tail cancer(PBTC)have different overall survival(OS),molecular signature and response to chemotherapy.METHODS We retrospectively queried patient records from July 2016 to June 2020 in our institution.Patient demographics,cancer stage on diagnosis,tumor location,somatic mutations,treatment,and survival are recorded and analyzed.A test is considered statistically significant if the P value was<0.05.RESULTS We reviewed 101 patients with complete records,among which 67(66.34%)were PHC and 34(33.66%)were PBTC.More PHC were diagnosed at younger age[61.49 vs 68.97,P=0.010],earlier stages(P=0.006)and underwent surgical resection(P=0.025).There were no significant differences among all mutations and pathways studied except for TP53 mutations(37.0%in PHC vs 70.0%in PBTC,P=0.03).OS was not statistically different between PHC and PBTC(P=0.636)in the overall population and in subgroups according to surgical resection status or stages.In terms of response to chemotherapy,chemotherapy regimens(FOLFIRINOX-based vs gemcitabine-based)didn’t impact disease free interval in those who had surgical resection in either PHC(P=0.546)or PBTC(P=0.654),or the duration of response to first line palliative treatment in those with advanced disease in PHC(P=0.915)or PBTC(P=0.524).CONCLUSION Even though PHC and PBTC have similar poor OS and response to chemotherapy,the different presentations and molecular profiles indicate they are different diseases.Utilization of molecular profiling to develop targeted therapy for individualization of treatment is needed.

关键词： Pancreatic cancer Tumor location Molecular profiling Survival Response to chemotherapy

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Chemotherapy rechallenge in metastatic colon cancer:A case report and literature review

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World Journal of Clinical Oncology 2020年第11期11卷 959-967页

作者： Tejaswini Parlapalle Reddy Usman Khan Ethan Alexander Burns Maen Abdelrahim College of Medicine Texas A&M University Health Science CenterBryanTX 77807United States Department of Medical Oncology Houston Methodist Hospital Cancer CenterHoustonTX 77030United States Section of GI Oncology Department of Medical OncologyHouston Methodist Cancer Center.Cockrell Center of Advanced Therapeutics Phase I ProgramHouston Methodist Research Institute and Weill Cornell Medical CollegeHoustonTX 77030United States

BACKGROUND Colorectal cancer(CRC)is the third leading cause of cancer-related death in males and females in the United States.Approximately,20%-22%of patients have metastatic disease at the time of presentation,and 50%-60%will develop metastasis over the course of their disease.Despite advances in systemic therapies,there remains a paucity of effective third-and later-line therapies for patients with ongoing disease progression.However,rechallenging chemoresistant CRC tumors with previously administered therapies is an emerging concept that may be a life-prolonging option for heavily treated metastatic colorectal cancer(mCRC).CASE SUMMARY A 41-year-old man with no previous medical history initially presented with worsening diffuse abdominal tenderness.Computed tomography was significant for a splenic flexure mass and hepatic lesions concerning for metastatic disease.He underwent a colectomy with anastomosis.Postoperative pathology was diagnostic for moderately to well-differentiated adenocarcinoma(T4bN1bM1a).He received adjuvant 5-fluorouracil,leucovorin,and oxaliplatin(FOLFOX),but therapy was discontinued due to the development of atrial fibrillation.Additional workup indicated a carcinoembryonic antigen level of 508.2 ng/mL,and mutational analysis found that the tumor was microsatellite instability-high and KRAS/BRAF wild-type.He was started on irinotecan with oxaliplatin(IROX),and bevacizumab(14 cycles),developed disease progression,was transitioned to FOLFOX and cetuximab,and then eventually three cycles of pembrolizumab.Following disease progression,he was rechallenged with IROX therapy,as he previously responded well to oxaliplatin-based therapy.The IROX rechallenge provided this patient with a ten-month survival benefit,decreased metastatic burden,and marked improvement in his clinical condition.CONCLUSION Rechallenge of previous lines of well-tolerated systemic chemotherapy regimens may be a valuable therapeutic strategy in patients with heavily-treated mCRC.

关键词： Metastatic colorectal cancer Rechallenge therapy Treatment holiday Oxaliplatin Irinotecan Case report Chemoresistance Palliative option

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