Prognostic value of the neutrophil/lymphocyte ratio in enteropancreatic neuroendocrine tumors.

Accessible prognostic tools are needed to individualize treatment of neuroendocrine tumors (NETs). Data suggest neutrophil/lymphocyte ratios (NLRs) have prognostic value in some solid tumors, including NETs. In the randomized double-blind CLARINET study (NCT00353496; EudraCT 2005-004904-35), the somatostatin analog lanreotide autogel/depot increased progression-free survival (PFS) compared with placebo in patients with inoperable or metastatic intestinal and pancreatic NETs (grades 1-2, Ki-67 < 10%). The exploratory post-hoc analyses presented here evaluated the prognostic value of NLR in the CLARINET study cohort, in the context of and independently from treatment. Kaplan-Meier PFS plots were generated for patients with available NLR data, in subgroups based on NLR values, and 24-month survival rates were calculated. P values and hazard ratios for prognostic effects were generated using Cox models. 31216222 Baseline characteristics were balanced between lanreotide autogel/depot 120 mg (n = 100) and placebo (n = 101) arms. Irrespective of treatment, raw 24-month PFS rates were comparable across subgroups based on NLR tertiles [37.3% (low), 38.8% (middle), 38.8% (high); n = 67 per group] and NLR cutoff of 4 [38.1% (NLR ≤ 4; n = 176), 40.0% (NLR > 4; n = 25)]. Furthermore, NLRs were not prognostic in Cox models, irrespective of subgroups used. The therapeutic effect of lanreotide autogel/depot 120 mg was independent of NLRs (P > 0.1). These exploratory post-hoc analyses in patients with advanced intestinal and pancreatic NETs contrast with previous data suggesting NLR has prognostic potential in NETs. This may reflect the inclusion of patients with lower-grade tumors or use of higher NLR cutoff values in the current analysis.

Hyponatremia Predicts Poor Outcomes in Patients With Chronic Kidney Disease Undergoing Heart Operation.

BACKGROUND: Preoperative hyponatremia adversely affects outcomes of cardiothoracic operation. However, in patients with chronic kidney disease, the association of sodium levels on postoperative events has never been evaluated. We investigated the impact of preoperative hyponatremia on outcomes after cardiac operation in patients with non-dialysis-dependent chronic kidney disease. Primary end points were operative mortality and acute kidney injury that required dialysis. Secondary end points were major infection and long-term survival. METHODS: The study is observational and includes all patients with stage III to IV chronic kidney disease (non-dialysis) undergoing cardiac operation between February 2000 and January 2016. Patients were stratified into two groups by preoperative sodium levels: sodium less than 135 mEq/L and sodium of 135 mEq/L or more. RESULTS: There were 1,008 patients (mean estimated glomerular filtration rate [GFR]: 43 ± 14 mL • min-1 • 1.73 m-2) with 92 patients (9%) in the low-sodium group. Patients with low sodium had higher operative mortality (p = 0.0004), need for new dialysis (p = 0.0008), and infection (p = 0.002). Predictors of operative mortality were European System for Cardiac Operative Risk Evaluation (EuroSCORE) (hazard ratio [HR] 1.03. 95% confidence interval [CI]: 1.02 to 1.05, p < 0.0001), decreasing values of sodium (HR 1.14. 95% CI: 1.07 to 1.2, p = 0.0002), and decreasing values of GFR (HR 1.01, 95% CI: 1.003 to 1.03, p = 0.007). Sodium less than 135 mEq/L was independently associated with increased need for dialysis (HR 1.3, 95% CI: 1.1 to 1.7, p = 0.0008). By linear regression, decreasing values of preoperative sodium were proportionate to the incidence of operative mortality (p < 0.0001) and need for dialysis (p < 0.0001). CONCLUSIONS: Preoperative hyponatremia is a predictor of increased mortality and other adverse events in patients with non-dialysis-dependent chronic kidney disease undergoing cardiac operation. These findings are similar to those in hyponatremic patients without kidney disease.

Neutrophil-Lymphocyte Ratio: Prognostic Impact in Heart Surgery. Early Outcomes and Late Survival.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a recognized marker of inflammation associated with poor outcomes in various clinical situations. We analyzed the prognostic significance of preoperative elevated NLR in patients undergoing cardiac surgery. METHODS: We performed a retrospective review of 3,027 consecutive patients undergoing cardiac surgery. Receiver-operating-characteristic was used to determine the cutoff value for elevated NLR. Multivariate regression was used to determine the predictive value of preoperative NLR on clinical outcomes. Cox proportional hazards functions were used to determine predictors of late events. Late survival data to 16 years was obtained from the Ministry of Interior. RESULTS: The cutoff value for elevated NLR was 2.6. Patients with elevated NLR were older (p < 0.0001), had a higher incidence of cardiac comorbidity (p < 0.0001), and higher European System for Cardiac Operative Risk Evaluation score (p < 0.0001). An elevated NLR emerged as an independent predictor of operative mortality (hazard ratio [HR] 2.15, 95% confidence interval [CI]: 1.51 to 3.08, p < 0.0001); pleural effusion (HR 1.42, 95% CI: 1.13 to 1.80, p = 0.003); low output syndrome (HR 1.54, 95% CI: 1.23 to 1.93, p = 0.0002); prolonged ventilation (HR 1.49, 95% CI: 1.23 to 1.82, p = 0.0001); or composite outcomes (HR 1.61, 95% CI: 1.36 to 1.91, p < 0.0001). The NLR emerged as an independent predictor of late mortality (HR 1.19, 95% CI: 1.11 to 1.28; p < 0.0001). CONCLUSIONS: Elevated NLR is associated with a higher incidence of adverse outcomes after cardiac surgery. It is a predictor of operative as well as late mortality. Further studies are warranted to determine whether prophylactic treatment with antiinflammatory agents can prevent such outcomes. It may be warranted to include the baseline NLR as another variable in risk stratification of patients about to undergo cardiac surgery.

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. MATERIALS AND METHODS: 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). RESULTS: An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. CONCLUSIONS: An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].

Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P<0.001) in the dexrazoxane group, but no significant difference in the incidence of treatment delays or cancellations. The incidence of cardiac events was the same in both treatment groups with and without dexrazoxane. There was a nonsignificantly lower mortality rate in the dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding dexrazoxane to doxorubicin in adjuvant therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions. No differences in events defined as cardiac toxicities were detected. Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the dexrazoxane group.

Derived neutrophil to lymphocyte ratio as a prognostic factor in patients with advanced colorectal cancer according to RAS and BRAF status: a post-hoc analysis of the MRC COIN study.

The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out. All patients with available white blood cell and neutrophil data were analysed. The dNLR was calculated using a formula that has previously shown predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined as a value of 2.2 or more. dNLR was correlated with clinical outcomes using Kaplan-Meier and Cox regression analysis. A total of 1603 patients were assigned to the oxaliplatin-based chemotherapy (arm A, N=815) or oxaliplatin-based chemotherapy plus cetuximab (arm B, N=815) arms. There was a strong association between dNLR level and overall survival (OS) using Kaplan-Meier analysis. In all mutation groups, dNLR less than 2.2 was associated with better OS compared to dNLR of 2.2 or more. The median OS in patients with wild-type disease (dNLR<2.2 vs. dNLR≥2.2) was 22.8 versus 13.1 months [hazard ratio (HR)=1.33]; 16.9 versus 11.8 months (HR=1.36) in patients with RAS mutant tumours; and 12.6 versus 6.8 months (HR=1.67) in patients with BRAF mutant tumours. In patients with dNLR less than 2.2, the median OS was 19.2 months in arm A compared to 18.0 months in arm B (HR=1.11). Among patients with dNLR greater than or equal to 2.2, the median OS was 13.0 months in arm A compared with 13.1 months in arm B (HR=0.96). dNLR is strongly prognostic for survival in all mutation groups. dNLR does not predict for benefit from the addition of cetuximab.

Immune Monitoring of Patients Treated With a Whole-Cell Melanoma Vaccine Engineered to Express 4-1BBL.

CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB-IV patients were vaccinated with a melanoma antigen-rich cell line engineered to express HLA-A2 and 4-1BBL (M20/A2/BBL). Twelve serially recruited patients were monitored for interferon γ expression and CD107a mobilization before and after vaccination. Thirty-three patients remained alive, with an estimated mean overall survival of 26.2 months. No grade 3-4 adverse events were encountered. Immune monitoring detected an increase in circulating antimelanoma CD8 T cells in 9 of 12 patients, which were significantly stimulated by the parental melanoma, reflecting a relevant antitumor response. The results from this study show that the costimulatory 4-1BB ligand fortifies an antigen-rich melanoma cell line with enhanced antigen-specific stimulation of CD8 T cells. The use of a costimulatory molecule as part of a vaccine confers a selective increase of T-cell subsets with antimelanoma reactivity, which in some cases were characterized for their epitope specificity.

Next-generation sequencing in patients with advanced cancer: are we ready for widespread clinical use? A single institute's experience.

The next-generation sequencing (NGS) assay targeting cancer-relevant genes has been adopted widely for use in patients with advanced cancer. The primary aim of this study was to assess the clinical utility of commercially available NGS. We retrospectively collected demographic and clinicopathologic data, recommended therapy, and clinical outcomes of 30 patients with a variety of advanced solid tumors referred to Foundation Medicine NGS. The initial pathologic examination was performed at the pathology department of the referring hospital. The comprehensive clinical NSG assay was performed on paraffin-embedded tumor samples using the Clinical Laboratory Improvement Amendments-certified FoundationOne platform. The median number of genomic alterations was 3 (0-19). The median number of therapies with potential benefit was 2 (0-8). In 12 cases, a comprehensive clinical NGS assay did not indicate any therapy with potential benefit according to the genomic profile. Ten of the 30 patients received treatments recommended by genomic profile results. In six of the 10 cases, disease progressed within 2 months and four patients died within 3 months of treatment initiation. Three of the 30 patients benefited from a comprehensive clinical NGS assay and the subsequent recommended therapy. The median PFS was 12 weeks (95% confidence interval 10-57) in patients treated with molecularly targeted agents chosen on the basis of tumor genomic profiling versus 48 weeks (95% confidence interval 8-38) in the control group treated with physician choice therapy (P=0.12). Our study suggests that NGS can detect additional treatment targets in individual patients, but prospective medical research and appropriate clinical guidelines for proper clinical use are vital.

Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.

BACKGROUND: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer. METHODS: A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR = ANC/(WBC-ANC). A high dNLR was defined using a cut-off value of ⩾ 2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan-Meier method. Comparison between groups was performed using Cox regression. RESULTS: A total of 1630 patients were assigned to the continuous (N = 815) or intermittent (N = 815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR = 1.70; 95% CI = 1.52-1.90; P < 0.001). The estimate of the hazard ratio did not alter substantially (HR = 1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count. CONCLUSIONS: Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy.

Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy.

PURPOSE: Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy. RESULTS: The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9±2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002). CONCLUSIONS: Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab.

Pegylated liposomal mitomycin C prodrug enhances tolerance of mitomycin C: a phase 1 study in advanced solid tumor patients.

Mitomycin C (MMC) has potent cytotoxicity but cumulative toxicity limits widespread use. In animals, pegylated liposomal mitomycin C lipid-based prodrug (PL-MLP) was well tolerated and more effective than free MMC. We evaluated PL-MLP in patients with advanced cancer. Twenty-seven patients were treated in escalating dose cohorts of 0.5-3.5 mg/kg (equivalent to 0.15-1.03 mg/kg MMC) every 4 weeks for up to 12 cycles, unless disease progression or unacceptable toxicity occurred. Pharmacokinetics were assessed during cycles 1 and 3. Per protocol maximum tolerated dose was not reached at 3.5 mg/kg. However, prolonged thrombocytopenia developed after repeated doses of 3 mg/kg or cumulative doses of 10-12 mg/kg. Dose-related grade 3 or higher adverse events included fatigue, anemia, and decreased platelets. Cmax and AUC0-∞ increased linearly over the dose range 0.5-2.0 mg/kg, and greater than linearly from 2.5 to 3.5 mg/kg; there were no significant differences in clearance of MLP between cycles 1 and 3. Median t1/2 was 23 h among dose cohorts, with no trend by dose or cycle. One patient had a partial response. Stable disease was observed in 10 patients across all dose levels. PL-MLP has a long circulation time, was well tolerated, and can be administered to heavily pretreated patients at a single dose of 3.0 mg/kg and cumulative dose of 10-12 mg/kg before development of prolonged thrombocytopenia; this is nearly threefold the equivalent dose of MMC tolerated historically. This formulation may be active in a variety of tumor types and is better tolerated than free MMC.

Predictive Value of the Neutrophil/Lymphocyte Ratio in Peritoneal and/or Metastatic Disease at Staging Laparoscopy for Gastric and Esophageal Adenocarcinoma.

BACKGROUND: Despite advances in imaging techniques, peritoneal and/or metastatic disease have been identified by staging laparoscopy in up to 50 % of patients with a negative preoperative imaging. Neutrophil to lymphocyte ratio (NLR) has been recently shown as a prognostic factor in gastric and esophageal cancers. METHODS: We retrospectively reviewed the medical records of 117 patients with early gastric and lower esophagus adenocarcinoma that were referred for staging laparoscopy in the last two years in the University College Hospital, London. Complete blood count was performed preceding staging laparoscopy. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; a high NLR was defined ≥3.28. We evaluated the predictive power of a high NLR for a positive staging laparoscopy. RESULTS: The median age was 66.7 years; 87 (74.4 %) were male. Forty-four percent of the tumors were located at the gastroesophageal junction, 18 % were esophageal, and 38 % were gastric. Twenty-five (21.4 %) patients were found to have peritoneal or metastatic disease on staging laparoscopy. NLR ≥3.28 was an independent predicting factor for the discovery of peritoneal and/or metastatic disease (OR 3.9, 95 % CI: 1.54-9.86, p = 0.005). The median value of NLR was significantly higher in patients for whom the laparoscopy had discovered peritoneal or metastatic disease, than in those it had not (3.3 vs. 2.2, p = 0.011). CONCLUSION: Our findings suggest that the NLR may be reliable for predicting the presence of peritoneal or metastatic involvement on staging laparoscopy, in patients with early gastric cancer or lower esophageal cancer.

The preoperative neutrophil/lymphocyte ratio does not correlate with the 21-gene recurrence score in estrogen receptor-positive breast cancer patients.

AIMS: The aim of this study was to examine the correlation, if any, between the preoperative neutrophil/lymphocyte ratio (NLR) and the OncotypeDX™ 21-gene recurrence score (RS) in patients with early-stage estrogen receptor (ER)-positive breast cancer (BC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients diagnosed with primary ER-positive BC who were referred for the RS assay. The correlation between the preoperative NLR and the RS was analyzed. RESULTS: For the 242 patients with sufficient data for analysis, the median age at diagnosis was 59.5 years. The tumor size ranged from 0.50 to 5.50 cm, with a mean size of 1.8 cm; 73.2% of the tumors were < 2 cm in size. Most of the tumors (66.3%) were of grade 2; the rest was nearly equally divided between grades 1 and 3. The test results for the progesterone receptor (PR) were positive in 86.6% of the cases. Lymph node metastases were present in 22.3% of the patients. The median RS was 18 (range 0-60) and the mean NLR value was 2.11 (range 0.49-7.49). We found no significant correlation between the NLR and the RS. CONCLUSION: Our data suggest that the preoperative NLR does not predict the 21-gene RS in patients with early-stage hormone-sensitive BC.

The 21-gene recurrence score assay (Oncotype DX™) in estrogen receptor-positive male breast cancer: experience in an Israeli cohort.

OBJECTIVE: The 21-gene recurrence score (RS) assay has been widely adopted for use in early estrogen receptor (ER)-positive breast cancer to assess the risk for distant recurrence and the potential benefit of adjuvant chemotherapy. The primary aim of this study was to assess RS distribution in Israeli male breast cancer (MBC) patients. METHODS: The study population included 65 newly diagnosed Israeli MBC patients. Clinical and pathologic data were collected at the time of referral. Pathologic examinations were conducted at the pathology departments of the referring centers. The RS assay (Oncotype DX™) was performed on paraffin-embedded tumor samples at Genomic Health laboratories. RESULTS: The mean age of the patients was 65.1 years (range 38-88 years). Low-risk (RS<18), intermediate-risk (RS 18-30) and high-risk (RS≥31) scores were noted in 29 patients (44.6%), 27 patients (41.5%) and 9 patients (13.9%), respectively. The distribution of RS in male patients was similar to the distribution in 2,455 female patients from Israel referred during the same time period. CONCLUSION: Our data suggest that the distribution of Oncotype DX RS in ER-positive MBC patients is similar to that of female breast cancer patients.

Clinical manifestations and outcome of ANCA-related pauci-immune glomerulonephritis in patients with Sjögren's syndrome.

OBJECTIVES: Pauci-immune ANCA-related glomerulonephritis (GN) is extremely uncommon in patients with underlying Sjögren's syndrome (SS) and its clinical and laboratory characteristics have not been previously explored. METHODS: We carried out a thorough literature review in order to establish predisposing factors, clinical and laboratory manifestations, kidney biopsy features, treatment modalities and response to treatment of biopsy proven ANCA-related pauci-immune GN in patients with SS. RESULTS: From 1967 to 2011, seven patients with a mean age of 63±14.7 years were identified. The average duration of SS prior to development of pauci-immune GN was 50±62 months. A high incidence of extraglandular manifestations was identified: 50% had interstitial lung disease and/or peripheral neuropathy. All patients suffered from proteinuria (average 1397±905 mg per 24 hours) and haematuria at presentation. Almost 70% of patients suffered from severe anaemia (average haemoglobin 6.6±1.9 gr%). ANCA MPO was positive in all six patients, while ANCA PR3 was negative in all. All patients received corticosteroids and 70% received cyclophosphamide. One patient died and one patient developed end stage kidney disease. The rest of the study patients had improved renal function over time. CONCLUSIONS: Our study emphasises that patients with SS can present with atypical kidney pathology as ANCA-related GN. Thus, high clinical awareness is warranted to establish correct diagnoses. Given the powerful impact of kidney pathology on management of these patients and responsiveness to treatment demonstrated in our case series, the significance of timely diagnosis can not be overestimated.

Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: retrospective analysis of a single institution experience.

The aim of the present retrospective study was to evaluate the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer (CRPC) and to identify predicting factors of response to DES. Patients treated with DES during the castration-resistant phase following the failure of prior treatment with LH-RH analogs during the castration-sensitive phase were retrieved from a prostate cancer database of our institution. Patients were treated with a daily dose of DES of 1-4 mg (mean, 2.6 mg) and anticoagulants for thromboembolic prophylaxis until disease progression. We analyzed their medical records, biochemical prostate-specific antigen (PSA) response and time to disease progression (TDP). Disease response and progression were identified according to the PCWG2 criteria. Patient data were examined using Kaplan-Meier survival analysis and statistical correlation tests with intra-patient comparison of the LH-RH and DES treatment phases. Forty-three DES-treated CRPC patients were found in our database through July 2011. The median age was 66 years. Sixty-three percent of the patients achieved a ≥50% decline in their serum PSA levels during DES therapy. Median TDP was 20.4 months for LH-RH analog treatment in the castration-sensitive phase, and 7.1 months for DES treatment in the castration-resistant phase. Durable responses (>1 year) were observed in 31% of the patients. Median overall survival was 57 months from the start of the DES therapy. There was no significant correlation between the TDP under LH-RH analogs and under DES therapy among the 38 patients eligible for correlation analysis. However, the magnitudes of serum PSA responses under DES and LH-RH analogs were significantly correlated with each other, and with the TDP under DES therapy. There were no treatment-related deaths. Four patients (9%) developed thromboembolic complications while under treatment, some of which appeared to be related to a discontinuation of thromboprophylaxis. In conclusion, DES confers substantial clinical benefit in the treatment of CRPC, with a relatively good safety profile when administered with thromboprophylaxis. The use of DES may be effective in CRPC, irrespective of the length of the hormone-sensitive period with LH-RH treatment. The magnitude of PSA response to previous treatment with LH-RH analogs, as well as to DES, was predictive of the duration of response to DES.

[Intravenous vinorelbine as first line chemotherapy in patients with castration-resistant prostate cancer].

BACKGROUND: Docetaxel-based chemotherapy remains the treatment of choice in castration-resistant prostate cancer (CRPC). Generally, elderly patients poorly tolerate these drugs. Vinorelbine has a favolable toxicity profile and may be useful in elderly or unfit patients with castration-resistant prostate cancer. PURPOSE: The aim of this retrospective analysis was to evaluate the efficacy and safety of vinorelbine in patients with CRPC. PATIENTS AND METHODS: We analyzed the medical records of patients with CRPC treated in our institution with intravenous vinorelbine as first line chemotherapy. RESULTS: A total of 25 patients were assessable for efficacy. The median age was 73 years (range, 51-87 years); 9 out of 25 patients (36%) had a > 50% reduction in PSA levels from baseline. Mean progression-free survival was 7.2 months. Mean overall survival was 20.7 months. Mean overall survival for 11 patients treated with second-line taxane-based chemotherapy was 27.5 months compared to 16.8 months for patients who did not receive second-line chemotherapy. Treatment was generally well tolerated. CONCLUSION: On the basis of this small retrospective survey, we conclude that intravenous vinorelbine seems to be a therapeutic option in elderly or unfit patients with CRPC.

Use of pregabalin in the management of chronic uremic pruritus.

CONTEXT: Uremic pruritus (UP) affects many patients suffering from chronic kidney disease (CKD) and has a negative impact on quality of life and survival. It has become increasingly evident that central transmission and sensitization processes similar to those observed in chronic pain are important mechanisms of pruritus. OBJECTIVES: To test the potential role of pregabalin in reducing the intensity of UP in CKD patients. METHODS: We prospectively collected data on CKD patients who suffered from severe intractable pruritus. Patients were asked to record the intensity of pruritus on a visual analogue scale. RESULTS: Twelve patients were studied. The average pretreatment pruritus score was 9.7 ± 0.9 and decreased to 3.7 ± 2.35, 3.2 ± 1.75, and 3 ± 1.5 after one, four, and 24 weeks of treatment, respectively (P < 0.05). The positive effect of pregabalin was demonstrated during the first week of therapy in six patients. Most patients required 25mg a day. Pregabalin was well tolerated, with somnolence and dizziness developing in two patients. CONCLUSION: We demonstrated dramatic improvement of long-standing UP after the initiation of pregabalin. We suggest that pregabalin can be used safely in CKD but careful titration of the dose is required to obtain an optimal response and minimize the possible adverse effects.

Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin.

AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma (ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years (range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve (AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were re-evaluated and responses to therapy based on computer tomography (CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS (V19). RESULTS: A median of 10 cycles (range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.