title: Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.
abstract: There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ferdousi
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Shazli
authors.initials: S
authors.lastname: Azmi
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom; Weill Cornell Medical College Qatar, Division of Research, Qatar Foundation, Education City, Doha, Qatar.
authors.forename: Ioannis Nikolaos
authors.initials: IN
authors.lastname: Petropoulos
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Hassan
authors.initials: H
authors.lastname: Fadavi
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom; Weill Cornell Medical College Qatar, Division of Research, Qatar Foundation, Education City, Doha, Qatar.
authors.forename: Georgios
authors.initials: G
authors.lastname: Ponirakis
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom; Department of Clinical Neurophysiology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.affiliation: The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Imaan
authors.initials: I
authors.lastname: Malik
authors.affiliation: The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Wasat
authors.initials: W
authors.lastname: Mansoor
authors.affiliation: Institute of Human Development, Centre for Endocrinology & Diabetes, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester, United Kingdom; Weill Cornell Medical College Qatar, Division of Research, Qatar Foundation, Education City, Doha, Qatar.
authors.forename: Rayaz Ahmed
authors.initials: RA
authors.lastname: Malik
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003080:Cold Temperature / Q000009:adverse effects; D003315:Cornea / Q000294:innervation*; D015251:Epirubicin / Q000008:administration & dosage; D004916:Erythromelalgia / Q000139:chemically induced / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008113:Liver Neoplasms / Q000503:physiopathology / Q000556:secondary; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D009416:Nerve Regeneration; D009431:Neural Conduction; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D000068878:Trastuzumab / Q000008:administration & dosage; D014732:Vibration / Q000009:adverse effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D015251:Epirubicin; D000069287:Capecitabine; D000068878:Trastuzumab; D002945:Cisplatin