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Hypervitaminosis B12 As an Additional Prognostic Indicator in Elderly Adults with a Neoplastic Disease: Report of a Case and Review of the Literature

2015; Wiley; Volume: 63; Issue: 10 Linguagem: Inglês

10.1111/jgs.13687

1532-5415

Abrar‐Ahmad Zulfiqar, A. Martin-Kleisch,

Neuroendocrine Tumor Research Advances

Journal of the American Geriatrics SocietyVolume 63, Issue 10 p. 2220-2221 Letters to the EditorFree Access Hypervitaminosis B12 As an Additional Prognostic Indicator in Elderly Adults with a Neoplastic Disease: Report of a Case and Review of the Literature Abrar-Ahmad Zulfiqar MD, Abrar-Ahmad Zulfiqar MD Department of Internal Medicine and Geriatrics, University Hospital of Reims, Reims, FranceSearch for more papers by this authorAurelien Martin-Kleisch, Aurelien Martin-Kleisch Department of Internal Medicine and Geriatrics, University Hospital of Reims, Reims, FranceSearch for more papers by this author Abrar-Ahmad Zulfiqar MD, Abrar-Ahmad Zulfiqar MD Department of Internal Medicine and Geriatrics, University Hospital of Reims, Reims, FranceSearch for more papers by this authorAurelien Martin-Kleisch, Aurelien Martin-Kleisch Department of Internal Medicine and Geriatrics, University Hospital of Reims, Reims, FranceSearch for more papers by this author First published: 20 October 2015 https://doi.org/10.1111/jgs.13687Citations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL To the Editor: Physicians are frequently asked questions about expected length of survival. Some illnesses are associated with a diagnosis that virtually always has a poor prognosis. Hypervitaminosis B12 is an unknown, for physicians, mostly early marker of serious diseases.1, 2 Case Presentation An 84-year-old woman was admitted to a geriatric unit after a fall. Notable medical history included treated hypertension. Physical examination revealed mitotic disease in the breast folds. Breast screening detected a painless, immobile swelling with a diameter of 5 cm in the left breast. No axillary lymphadenopathy was found. Laboratory tests found vitamin B12 levels of 2,000 pg/mL (normal 191–663 pg/mL), combined with moderate biological inflammatory syndrome (C-reactive protein (CRP) 26 mmol/L; normal <10 mmol/L). A mammogram coupled with ultrasound showed a hypoechogenetic tissue mass, with irregular contours at the left inframammary level, American College of Radiology Class 5. Left breast biopsy showed infiltrating ductal carcinoma, Scarff Bloom Richardson grade II, mitotic index 2, estrogen receptor positive 100%, progestin receptors positive 50%, and human epidermal growth factor receptor 2 negative. No carcinomatous emboli were found. Thoracoabdominopelvic computed tomography revealed secondary metastases in the lung, liver, and bones. Cerebral scans did not show brain metastases. Multimetastatic breast cancer (tumoral classification pT2 N0 M+) was diagnosed and could explain this hypervitaminosis B12. Her Palliative Prognostic Score (PPS; range 0–1.75) was 1.5, which indicated a 30 to 70% likelihood of 30-day survival, and her Palliative Prognostic Index (PPI) was 2.5 (PPI < 4 is associated with survival >6 weeks). After oncogeriatric assessment, hormonal treatment was prescribed (anastrozole), but her prognosis was poor. Discussion An association between hypervitaminosis B12 and solid neoplasms was demonstrated in a study of vitamin B12 and haptocorrin levels in a population of 139 individuals with malignant disease.3 The main relevant cancers are hepatocellular carcinoma (HCC) and secondary liver tumors, breast cancer, colon cancer, stomach cancer, and pancreatic tumors.1, 2 Pathophysiologically, in solid tumors, hypervitaminosis B12 is mainly linked to excessive synthesis of transcobalamins by the tumor or high haptocorrin levels due to leukocytosis reaction.1 Hypervitaminosis B12 has also been described as a potential tumor marker of poor prognosis.4 A previous study5 found strong predictive value for mortality for hypervitaminosis B12 in individuals with cancer receiving palliative care. A study of the prognosis of people with cancer and hypervitaminosis B12 found a strong association between hypervitaminosis B12 and poor prognosis, with a median survival of approximately 1 month. Metastases were also more frequent in this subgroup.6 Likewise, another study found greater mortality associated with high levels of vitamin B12 in a series of 1,570 individuals aged 65 and older admitted to a geriatric ward.7 It has been suggested that vitamin B12 levels be used as a tool in investigative and therapeutic decision-making, especially in severely ill individuals or those with chronic disease.6 Prognostic value has been attributed to vitamin B12 in cancer, and an index, the vitamin B12/CRP Index (BCI), has been developed that has a high predictive value for mortality in cancer in palliative care (P < .001).6 A BCI greater than 40,000 was associated with 90% mortality at 3 months. The highest rate was associated with the highest mortality.6 A study of 329 individuals with advanced cancer confirmed these findings, with 29-day median survival in those with a BCI greater than 40,000 (P < .01).8 The BCI of the woman described above was estimated at 52,200. The BCI should be considered as an additional prognostic indicator, alongside the PPS 9 and the PPI.10 The PPI consists of a weighted scale assessing five clinical variables (performance status, oral intake, edema, dyspnea at rest, delirium).10 These two instruments do not include clinician estimates as an independent prognostic factor. Moreover, BCI does not rely on subjective estimates of symptom severity or clinician estimates of survival.8 Conclusion Further exploratory studies are warranted to explore serum vitamin B12 and the BCI as a tool in investigative and therapeutic decision-making and to develop new prognostic scales for elderly adults. Acknowledgments Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Zulfiqar: study concept and design, acquisition of subjects and data, data analysis and interpretation, preparation of manuscript. Martin-Kleisch: acquisition of subjects and data, data analysis and interpretation, preparation of manuscript. Sponsor's Role: None. References 1Andrès E, Serraj K, Zhu J et al. The pathophysiology of elevated vitamin B12 in clinical practice. QJM 2013; 106: 505– 515. 2Zulfiqar AA, Sebaux A, Andrès E et al. Hypervitaminia B12: An unknown endocrine marker. J Food Nutr Sci 2015; 3: 32– 34. 3Carmel R. Extreme elevation of serum transcobalamin I in patients with metastatic cancer. N Engl J Med 1975; 292: 282– 284. 4Arendt JFB, Pedersen L, Nexo E et al. Elevated plasma vitamin B12 Levels as a marker for cancer: A population-based cohort study. J Natl Cancer Inst 2013; 105: 1799– 1805. 5Kane SP, Murray-Lyon IM, Paradinas FJ et al. Vitamin B12 binding protein as a tumour marker for hepatocellular carcinoma. Gut 1978; 19: 1105– 1109. 6Geissbühler P, Mermillod B, Rapin C-H. Elevated serum vitamin B12 levels associated with CRP as a predictive factor of mortality in palliative care cancer patients: A prospective study over five years. J Pain Symptom Manage 2000; 20: 93– 103. 7Tal S, Shavit Y, Stern F et al. Association between vitamin B12 levels and mortality in hospitalized older adults. J Am Geriatr Soc 2010; 58: 523– 526. 8Kelly L, White S, Stone PC. The B12/CRP index as a simple prognostic indicator in patients with advanced cancer: A confirmatory study. Ann Oncol 2007; 18: 1395– 1399. 9Pirovano M, Maltoni M, Nanni O et al. A new palliative prognostic score: A first step for the staging of terminally ill cancer patients. Italian Multicenter and Study Group on Palliative Care. J Pain Symptom Manage 1999; 17: 231– 239. 10Morita T, Tsunoda J, Inoue S et al. The Palliative Prognostic Index: A scoring system for survival prediction of terminally ill cancer patients. Support Care Cancer 1999; 7: 128– 133. Citing Literature Volume63, Issue10October 2015Pages 2220-2221 ReferencesRelatedInformation