Urothelial carcinoma of donor origin in a kidney transplant patient.

BACKGROUND: Malignancy after transplantation is an uncommon multifactorial occurrence. Immunosuppression to prevent graft rejection is described as a major risk factor in malignancy development in the post-transplant state. Donor-derived malignancy is a rare reported complication. Herein, we review our patient history and discuss diagnostic strategies and the implications of immunosuppression for donor-derived malignancy. CASE PRESENTATION: This is a 69-year-old man with post-renal-transplant urothelial carcinoma determined to be of donor origin. His course was complicated by BK virus at six years post-transplant; urothelial carcinoma was identified nine years post-transplant. Cystectomy was performed, but because of immunosuppression and underlying chronic kidney disease, the patient was considered ineligible for adjuvant chemotherapy. Two years after resection, screening MRI demonstrated retroperitoneal lymphadenopathy and a right upper pole mass in the transplanted kidney. Urine cytology confirmed the presence of malignant cells; FISH showed 2-8 copies of the X chromosome and no Y chromosome consistent with female origin of the malignant cells. CT-guided renal mass and paraaortic lymph node biopsies demonstrated that about 50 % of cells had an XY complement, while the remainder showed a XX genotype by chromosomal SNP microarray analysis. Immunosuppression was discontinued and the donor kidney removed. X/Y FISH of the urothelial carcinoma identified in the explanted kidney confirmed that the malignant cells were of female donor origin. Follow-up at 3, 6 and 12 months after discontinuation of immunosuppression and surgery demonstrated normalization of the lymphadenopathy and absence of new lesions. CONCLUSIONS: Immunosuppression is a major risk factor for development of malignancy in transplant recipients. Donor-derived malignancy can arise and current molecular studies allow an accurate diagnosis. Withdrawal of immunosuppression and surgical resection of the transplant kidney proved an effective treatment in our case.

Central Nervous System Metastases in Patients With Cervical Carcinoma.

INTRODUCTION: Cervical cancer (CC) is the most common malignancy throughout developing countries, although considered rare, central nervous system metastasis (CNSm) does occur. OBJECTIVE: This study aimed to describe our experiences and compare them to other published cases. MATERIALS AND METHODS: From May 2009 to August 2015, the files of all patients with CC treated at our referral center were reviewed. RESULTS: We found 27 patients with CC and CNSm. Mean age at the time of CNS diagnosis was 50 ± 11 years, mean interval between initial CC and CNSm was 46 months; the most frequent initial International Federation of Gynecology and Obstetrics stage was IIB with 17 patients followed by IB in 4. Fifty-nine percent of patients had lung metastases at the time CNSm were diagnosed. Headache was the most common symptom, followed by weakness, altered mental status, and ataxia/cerebellar. Mean survival was 8.2 months after CNSm was discovered; 3 patients are still alive. CONCLUSIONS: The present study describes the largest series of patients with CNSm from CC; this rare complication should be suspected in patients with CC who present with headache, ataxia, cranial nerve palsy, visual disturbance, altered mental status, focal weakness, or other neurological symptom, without other plausible explanation.

Nivolumab in renal cell carcinoma.

INTRODUCTION: Immune-based therapies (e.g., IL-2, IFN) have been used for some time in advanced clear cell renal cell carcinoma (RCC) with overall modest success. Recent advances have demonstrated that tumor cells evade immune-mediated destruction by inducing inhibitory signals that result in effector T-cell exhaustion. One mechanism involves interaction between the T-cell programmed death-1 (PD-1) receptor and its ligand, PD ligand-1, expressed on tumor and inflammatory cells. Nivolumab , an anti-PD-1 antibody, blocks this pathway, thereby reversing T-cell suppression and activating antitumor responses. AREAS COVERED: In this review, the authors summarize selected aspects of PD-1 signaling, the development of immune checkpoint therapeutic agents, and clinical data regarding the safety and efficacy of nivolumab in RCC from Phase I and II clinical trials. EXPERT OPINION: Objective responses and safety profiles of single-agent nivolumab are favorable in patients with previously treated and treatment-naive metastatic RCC. Combination therapies involving nivolumab are ongoing and have generated encouraging results. The use of nivolumab will have substantial impact on the management of patients with RCC.

Spontaneous coronary artery dissection in an elderly woman presenting with chest pain and positive cardiac biomarkers.

A 68-year-old African American female with a prior medical history of hypertension and dyslipidemia presented with sudden onset pressure-like substernal chest pain. Initial ECG showed no ST or T wave abnormalities, and troponin elevation of 2.88 ng/mL. Two hours later, chest pain recurred with ECG change and increase in troponin to 11.97 ng/mL. She underwent urgent coronary angiography, which revealed left anterior descending artery dissection with thrombus. We successfully treated with balloon angioplasty followed by placement of 3 drug-eluting stents resulting in TIMI-3 flow; further testing for vasculitis was negative. Once spontaneous coronary artery dissection is diagnosed, the approach to treatment is controversial and treatment should be patient tailored.

High response of second-line chemotherapy with pemetrexed or gemcitabine combined with carboplatin in patients with non-small-cell lung cancer experiencing progression following 6 months after concluding platinum-based chemotherapy.

Because of improved therapeutic results after first-line platinum-based chemotherapy in patients with stage IV non-small-cell lung cancer (NSCLC), second-line chemotherapy may be considered for a growing number of patients. Approximately, 10% of patients have an interval time after concluding first-line platinum-based chemotherapy greater than 6 months. These patients may achieve high tumor responses when platinum is again used in second-line treatment. Twenty-three patients experiencing progression following 6 months after concluding platinum-based chemotherapy were managed with second-line treatment with carboplatin combined with gemcitabine or pemetrexed. Overall response, progression-free survival (PFS), and overall survival (OS) after initiation of second-line treatment were calculated for all patients. Median PFS after first-line treatment was 12.6 months (95% confidence interval [95% CI], 10.4-14.7 months). Partial response was achieved in 7 of 23 patients, resulting in an overall response of 30.4% (95% CI, 11.6-49.0). Following initiation of second-line chemotherapy, median PFS was 5.9 months (95% CI, 1-10.9 months) and median OS was 12.5 months (95% CI, 3.5-21.5 months). The 1-year survival rate for all patients was 61.0% (95% CI, 29.5-82.0). Adding these results to those of the 10 previously published trials, 75 of 326 patients, 23%, (95% CI, 18.7-27.3) presented an overall response with the use of second-line platinum-based chemotherapy. The use of platinum combinations as second-line chemotherapy seems to have a place in the management of patients with advanced NSCLC, especially those with an interval time to progression greater than 6 months.

Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study.

BACKGROUND: A frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC. METHODS: We prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (175 mg/m2) and cisplatin (80 mg/m2). Malnutrition was assessed using SGA prior treatment. Neutrophil Lymphocyte Ratio (NLR) and the Platelet Lymphocyte Ratio (PLR) were used to determine the presence of systemic inflammatory response (SIR) and were related to the development of toxicity. Toxicity was graded according to NCI CTCAE version 3.0 after two chemotherapy cycles. RESULTS: Median age was 58 +/- 10 years, 51% of patients were malnourished, 50% had albumin < or =3.0 mg/mL. NLR > or = 5 was associated with basal hypoalbuminemia (mean ranks, 55.7 vs. 39 p = 0.006), ECOG = 2 (47.2 vs. 55.4 p = 0.026) and PLR > or = 150 were significantly related with a basal body mass index < or =20 (56.6 vs. 43.5; p = 0.02) and hypoalbuminemia (58.9 vs. 41.3; p = 0.02). Main toxicities observed after 2 cycles of chemotherapy were alopecia (84%), nausea (49%), neuropathy (46%), anemia (33%), lymphopenia (31%), and leukopenia (30%). Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition (31 vs 22; p = 0.02) and normal albumin (mean ranks, 62 vs 43; p = 0.002), respectively. Hypoalbuminemia was associated with anemia (56 vs 47; p = 0.05), fatigue (58 vs 46; p = 0.01), and appetite loss (57.1 vs 46.7; p = 0.004) compared with normal albumin. PLR > or = 150 was related with the development of toxicity grade III/IV (59.27 vs. 47.03 p = 0.008) and anemia (37.9 vs 53.8 p = 0.004). CONCLUSION: SIR parameters were associated with malnutrition, weight loss and hypoalbuminemia. Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia. Early nutritional assessment and support might confer beneficial effects.