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Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.
Zeng, MF, Chen, LL, Ye, HY, Gong, W, Zhou, LN, Li, YM, Zhao, XL
Medicine. 2017;(44):e8426
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Abstract
RATIONALE Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland. DIAGNOSES Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively. INTERVENTIONS Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval. OUTCOMES The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time. LESSONS The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.
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[Rhabdomyolysis after radical nephrectomy in the lateral decubitus position: report of 2 cases].
Shibamori, K, Yamamoto, T, Matsuki, M, Matsuda, Y, Kato, S, Takei, F, Yanase, M
Nihon Hinyokika Gakkai zasshi. The japanese journal of urology. 2014;(4):218-23
Abstract
Rhabdomyolysis is a rare perioperative complication, however, potentially lead to fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old man was seen in our hospital because of asymptomatic grosshematuria. Computed tomography revealed right renal pelvic cancer, cT3N0M0. Right radical nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and the operation was finished without any trouble. At the post-operative day 1, serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive-care unit (ICU), and serum creatinine and creatine kinase level were decreased. At the post-operative day 1, urine myoglobin level was prominently elevated (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case 2) A 40-years old man was incidentally pointed out of right renal tumor that was seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent, and there was no trouble during the operation. After recovering from anesthesia, the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L after the operation. At the postoperative day 1, serum creatine kinase level was markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml, respectively). We diagnosed it rhabdomyolysis, and he received large amount of fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed.
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Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma.
Fairfax, BP, Pratap, S, Roberts, IS, Collier, J, Kaplan, R, Meade, AM, Ritchie, AW, Eisen, T, Macaulay, VM, Protheroe, A
BMC cancer. 2012;:590
Abstract
BACKGROUND Sorafenib is an orally available kinase inhibitor with activity at Raf, PDGFβ and VEGF receptors that is licensed for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Current evidence-based post-nephrectomy management of individuals with localized RCC consists of surveillance-based follow up. The SORCE trial is designed to investigate whether treatment with adjuvant sorafenib can reduce recurrence rates in this cohort. CASE PRESENTATION Here we report an idiosyncratic reaction to sorafenib resulting in fatal hepatotoxicity and associated renal failure in a 62 year-old man treated with sorafenib within the SORCE trial. CONCLUSION This is the first reported case of sorafenib exposure associated fatal toxicity in the adjuvant setting and highlights the unpredictable adverse effects of novel adjuvant therapies.
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[Interferon alpha and half-dose sorafenib is an effective treatment modality for interferon alpha-resistant metastatic renal cell carcinoma: a case report].
Furuya, N, Kamai, T, Tokui, N, Abe, H, Fukabori, Y, Yoshida, K
Hinyokika kiyo. Acta urologica Japonica. 2009;(6):323-6
Abstract
Metastatic renal cell carcinoma is notoriously resistant to chemotherapy and radiotherapy. Immunotherapy with interferon alpha is widely used for the disease, but its treatment effects are poor. A 69-year-old Japanese women presented with gross hematuria. Imaging studies revealed a left renal tumor, 12 cm in diameter, and multiple pulmonary and hepatic lesions. No abnormal laboratory data were observed other than anemia with Hb 9.2 g/dl. Performance status was 0. She underwent radial left nepherectomy. Pathological examination showed clear cell renal cell carcinoma with moderate histological differentiation (grade 2) and microscopic vessel invasion; pT3aN0M1 (Pul, Hep). Memorial Sloon-Kettering Cancer Center classification was an intermediate risk due to anemia. She received interferon alpha, 5 million IU three times per week, postoperatively. In three months, hepatic lesions rapidly progressed although there was no interval change of pulmonary lesions. Then, the patient received interferon alpha at the same dose as described above and half-dose sorafenib, 400 mg per day. Grade 2 hypertension was under control by calcium channel blocker and the hand-foot syndrome was not obvious. No other grade 3/4 drug-related adverse events were observed. In one month after combination therapy, not only pulmonary lesions but also hepatic lesions were smaller. She has received this combination therapy with stable disease for six months. Performance status was 1 with grade 1 fatigue. The doses of this regimen may be tolerable, and might be an available treatment option for interferon alpha-resistant advanced renal cancer.
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Role of bariatric surgery in early detection of renal cell carcinoma: report of two cases and review of the literature.
Pilone, V, Tramontano, S, Formato, A, Mazzeo, M, Monda, A, Perone, M, Iacobelli, L, Forestieri, P
Chirurgia italiana. 2008;(5):703-9
Abstract
Obesity is considered a strong risk factor for renal cell carcinoma, the most common primary renal malignant neoplasm. An association between renal cell carcinoma and obesity has been reported in numerous trials. Several potential mechanisms may be responsible for the risk of renal cell carcinoma in obese subjects. We report the cases of two patients, submitted to bariatric malabsorbtive surgery, who presented a renal clear cell carcinoma several months after the operation. The diagnosis was made by routine postoperative ultrasound examination and confirmed by computed tomography in both cases. Both were treated surgically. Our approach after diagnosis of cancer consisted in evaluation of the patient's immunological, metabolic and nutritional status to establish whether it was a case of real malnutrition or an oncological risk condition. We judged that restoration of original gastrointestinal continuity was not necessary. In the literature, we found no evidence of an association between a cancer histotype and bariatric surgery. Confirming the association between renal cell carcinoma and morbid obesity, these case reports indicate the importance of imaging control, especially with non-invasive diagnostic studies, in high-risk cancer patients, such as obese patients, to detect lesions incidentally at an early stage. After a thorough review of the literature data, we consider bariatric patients a suitable group to be assessed for an early diagnosis of various types of cancer, detectable at preoperative or postoperative screening. Weight loss and continuous instrumental exams are conditions favourable to an early diagnosis. Guidelines regarding the management of oncological patients with a history of bariatric surgery are indispensable.
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Intravenously administered vitamin C as cancer therapy: three cases.
Padayatty, SJ, Riordan, HD, Hewitt, SM, Katz, A, Hoffer, LJ, Levine, M
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2006;(7):937-42
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Abstract
Early clinical studies showed that high-dose vitamin C, given by intravenous and oral routes, may improve symptoms and prolong life in patients with terminal cancer. Double-blind placebo-controlled studies of oral vitamin C therapy showed no benefit. Recent evidence shows that oral administration of the maximum tolerated dose of vitamin C (18 g/d) produces peak plasma concentrations of only 220 micromol/L, whereas intravenous administration of the same dose produces plasma concentrations about 25-fold higher. Larger doses (50-100 g) given intravenously may result in plasma concentrations of about 14,000 micromol/L. At concentrations above 1000 micromol/L, vitamin C is toxic to some cancer cells but not to normal cells in vitro. We found 3 well-documented cases of advanced cancers, confirmed by histopathologic review, where patients had unexpectedly long survival times after receiving high-dose intravenous vitamin C therapy. We examined clinical details of each case in accordance with National Cancer Institute (NCI) Best Case Series guidelines. Tumour pathology was verified by pathologists at the NCI who were unaware of diagnosis or treatment. In light of recent clinical pharmacokinetic findings and in vitro evidence of anti-tumour mechanisms, these case reports indicate that the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed.