Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A Single Site Trial.

INTRODUCTION: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative to whole breast radiation therapy following breast-conserving surgery for selected low-risk patients. However, minimal data are available about the clinical effectiveness of this modality of treatment using the Xoft® Axxent® Electronic Brachytherapy (eBx®) System®. METHODS: A total of 201 patients with 204 early-stage breast cancers were enrolled in a prospective X-ray IORT trial from June 2010 to September 2013. All tumors were treated with breast-conserving surgery and IORT. Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. RESULTS: With a median follow-up of 50 months, there have been seven ipsilateral breast tumor events (IBTE), no regional or distant recurrences, and no breast cancer-related deaths. One IBTE was within the IORT field, four outside of the IORT field but within the same quadrant as the index cancer, and two were new biologically different cancers in different quadrants. Three events were in patients who deviated from the protocol criteria. Kaplan-Meier analysis projects that 2.9% of patients will recur locally at 4 years. CONCLUSIONS: Recurrence rates observed in this trial were comparable to those of the TARGIT-A and ELIOT trials as well as the retrospective TARGIT-R trial. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of IORT in selected women with low-risk breast cancer.

Acute and Chronic Complications in Breast Cancer Patients Treated with Intraoperative Radiation Therapy.

INTRODUCTION: Intraoperative radiation therapy (IORT) permits the delivery of radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available about the complications associated with this modality of treatment using the Xoft(®) Axxent Electronic Brachytherapy (Axxent) System. METHODS: A total of 702 patients who received IORT using the Xoft(®) Axxent System at Hoag Memorial Hospital Presbyterian between June 2010-February 2016 were accrued in an IORT data registry study. The prospective and retrospective protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 3 months, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. RESULTS: Acute complications were observed in 21 % of patients and included hematomas that required drainage, seromas requiring drainage more than 3 times, infections treated with antibiotics or surgery, necrosis requiring surgery, and erythema. Chronic complications were observed in 13 % of patients and included seromas, fibrosis, and hyperpigmentation. The majority of acute and chronic problems from IORT were mild. If grade I erythema, fibrosis, and hyperpigmentation were removed, only 32 of 702 (4.6 %) had significant complications. Our complication rates were comparable to those of the TARGIT trial. CONCLUSIONS: IORT is a modality that safely delivers radiation therapy to patients diagnosed with breast cancer. This technique allows women who cannot (or decline to) undergo whole breast radiation to consider breast-conserving therapy rather than mastectomy.

Acute and Chronic Complications in Patients with Ductal Carcinoma in Situ Treated with Intraoperative Radiation Therapy.

Intraoperative radiation therapy (IORT) delivers radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available regarding IORT complications in patients diagnosed with ductal carcinoma in situ (DCIS) using the Xoft® Axxent eBx® System. 146 patients with pure DCIS received X-ray based IORT therapy using the Xoft® Axxent eBx® System at Hoag Memorial Hospital Presbyterian between June 2010 to April 2016 and were accrued to an IORT data registry study. The protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. Acute complications were observed in 18% of patients and included hematomas that required drainage, an infection treated with antibiotics, and erythema. Chronic complications were observed in 12% of patients and included a seroma, fibrosis and hyperpigmentation. The majority of acute and chronic problems were mild (Grade I). If Grade I erythema, fibrosis, and hyperpigmentation are not included, only 11/146 patients (7.5%) had significant complications. The rate of acute and chronic complications from X-ray IORT in DCIS patients was low compared to historical toxicity rates observed in DCIS patients treated with whole breast irradiation. Our data indicate that X-ray IORT can be utilized safely in patients diagnosed with DCIS.

Gene Expression Profile of Stromal Factors in Cancer-Associated Fibroblasts from Prostate Cancer.

Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) compared with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH). Three patient populations were prospectively recruited: 23 patients with new localized PCa, 14 patients with advanced PCa treated with androgenic deprivation therapy (ADT), and 7 patients with BPH. Gene expression of 20 stroma-derived factors, including the androgen receptor (AR), chaperones (HSPA1A and HSF1), growth factors (FGF2, FGF7, FGF10, HGF, PDGFB, and TGFß), proteins implicated in invasion (MMP2, MMP9, and MMP11), inflammation (IL6, IL17RB, NFκB, and STAT3), and in-stroma/epithelium interaction (CDH11, CXCL12, CXCL14, and FAP), was evaluated. Localized PCa CAFs showed a significant higher expression of FGF7, IL6, MMP2, and MMP11 compared with NAFs or IL17RB compared with BPH fibroblasts, but significantly lower expression of FGF10 and IL17RB compared with NAFs or CXCL14 compared with BPH fibroblasts. In addition, CAFs from ADT-resistant PCa showed significantly higher MMP11 and NFκB but significant lower TGFß expression compared with CAFs from ADT-sensitive tumors. Our results contribute to defining the CAFs phenotypes associated to PCa progression, which may contribute to the diagnosis and design of alternative therapies in PCa.

[Incidence of genitourinary pathology in the emergency department.] / Incidencia de la patología genitourinaria en urgencias.

OBJECTIVE: The increase of healthcare pressure in Emergency Departments compels us to have a better understanding of patients' characteristics and the pathology they consult for. This is the first study that estimates the waiting time in the emergency room and the factors that are independently related with hospital admission. METHODS: Descriptive and retrospective study of 2.741 patients who were admitted to the Emergency Department with genitourinary symptoms in 2011. Clinical and epidemiological features were reviewed. A multivariable study was performed to identify the factors related with the final resolution of patients, recurrence emergency attendance, and waiting time in the emergency room. RESULTS: Most of the patients were male (60.3%), being diagnosed with hematuria, acute urinary retention and genital pathology. Females complained more frequently for pyelonephritis, urinary tract infection and low-back pain. Male were hospitalized in greater proportion. Age, diagnosis of infection/sepsis or low-back pain, and yellow or orange MTS level were independent features for hospital admission. Also, in the univariate and multivariate study, age > 60 years (311 vs 220 min.), UTI/sepsis related diagnoses (300 vs 250 min.), and hospital admission as final resolution (440 vs 240 min.) had a significant influence in the waiting time in the Emergency Department. CONCLUSIONS: Age over 60 years, hospital admission as final resolution and infection/sepsis diagnosis were independent features for further waiting time in the Emergency Department. Persistent pain and symptoms of infection/sepsis behaved as independent features for hospital admission.

OBJETIVO: El aumento de la presión asistencial de los servicios de urgencias hospitalarios obliga a conocer las características de los pacientes y de los procesos por los que acuden. Este estudio es el primero que calcula tiempo de permanencia en urgencias y factores que se relacionan de manera independiente con ingreso hospitalario.MÉTODOS: Estudio descriptivo y retrospectivo de 2.741 pacientes que acudieron a Urgencias por sintomatología genitourinaria en el año 2011. Se examinaron rasgos clínicos y epidemiológicos. Se realizó un análisis multivariable para conocer los factores relacionados con la resolución final de los pacientes, recurrencia en la asistencia a urgencias y tiempo en urgencias. RESULTADOS: La mayoría de pacientes fueron varones (60,3%), con diagnósticos de hematuria, RAO y patología genital. Las mujeres, presentaron pielonefritis, ITU y dolor lumbar de manera más frecuente. Los varones ingresaron en mayor proporción. La edad, el diagnóstico de infección/sepsis o dolor lumbar y un nivel MTS amarillo o naranja, resultaron ser factores independientes de ingreso. Tanto en el estudio univariable como multivariable, la edad mayor de 60 años (311 vs 220 min), los diagnósticos relacionados con ITU y sepsis (300 vs 250 min) y el ingreso hospitalario como resolución final (440 vs 240 min) influyeron de forma significativa en el tiempo de estancia en Urgencias. CONCLUSIONES: La edad > 60 años, el resultado de ingreso y el diagnóstico de infección/sepsis fueron factores independientes de mayor tiempo en Urgencias. La presencia de dolor persistente y de infección/sepsis se comportaron como factores independientes de ingreso.

[Usefulness of cold ureteral biopsy during radical cystectomy as a predictor of recurrence risk: Review of our series.] / Utilidad de la biopsia fría ureteral durante la cistectomía radical como predictor de riesgo de recidiva: revisión de nuestra serie.

OBJECTIVES: To evaluate the association of positive margins in the intraoperative biopsy during radical cystectomy (RC) with the risk of recurrence in the uretero-ileal anastomosis or upper urinary tract (UUT), and identify potential risk factors for positive ureteral margins. METHODS: A retrospective, descriptive study was performed in patients treated with radical cystectomy due to transitional cell carcinoma (TCC), who underwent a cold biopsy of the ureteral margin at the time of cystectomy. A descriptive analysis and frequency distribution was performed. Fisher's test was used to calculate sensitivity and specificity and a survival analysis was performed. RESULTS: 230 patients were included. Prior to RC, transurethral resection of the bladder tumor and a CT scan were done. The percentage of positive margins was 4.81% for the right ureter and 4.27% for the left. Recurrence was detected in the anastomosis in 2.64% of the cases. In a 0.88% recurrence was found in the UUT (2 cases) at the level of left renal pelvis (1 case) and left kidney (1 case). In the multivariate analysis, neither recurrence in the anastomosis (p=1) or at the UUT (p=1) level during follow-up were significantly associated with the presence of positive margins. An association was found between the pathological biopsy of the right ureter and carcinoma in situ (CIS) of the bladder wall with UUT involvement. We found only association between the cold biopsy of the left ureter and tumor in left UTT. Reimplantation with positive margins was not statistically associated with neither ureteroileal anastomosis or UTT relapse. A relationship was found between the cold biopsy of both ureters and the definitive pathology. CONCLUSIONS: In our study, the presence of positive ureteral margins was not associated with an increased risk of recurrence in the anastomosis or UUT. Although it remains a topic for debate, a strategy to follow may be to adapt ureteral cold biopsies to individual risk, thus perform it in patients with bladder CIS.

Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment.

In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials. Pooled data confirmed that overall survival (OS) was longer in 72 patients treated with DC-TC compared with 71 patients treated with TC (median OS 60 versus 22 months; 5-year OS 51% versus 32%, p=0.004). Treatment with DC-TC was associated with longer OS in both cohorts. Among 70 patients who were NED at the time that treatment was started, OS was better for DC-TC: 5-year OS 73% versus 43% (p=0.015). Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025). This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.

Treatment of human solid malignancies with autologous activated lymphocytes and cimetidine: a phase II trial of the cancer biotherapy research group.

OBJECTIVE: The Cancer Biotherapy Research Group conducted a clinical trial to verify encouraging reports of antitumor activity of autolymphocyte therapy. PATIENTS AND METHODS: Patients with a variety of advanced solid malignancies underwent an initial leukapheresis procedure to collect about 5 x 10(9) autologous lymphocytes that were stimulated in vitro for 3 days with anti-CD3 monoclonal antibody in the presence of indomethicin and cis-retinoic acid to obtain media that was frozen in aliquots. This media contained significant amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, interferon-gamma, and IL6, but no IL-2. Subsequently patients underwent up to 6 monthly leukaphereses to collect 2-5 x 10(9) autologous lymphocytes that were incubated in vitro for 6 days in the cryopreserved media containing autologous lymphokines, resulting in a cell population enriched for noncytotoxic T-helper lymphocytes. These were administered intravenously monthly for up to 6 months with daily oral cimetidine at a dose of 600 mg po qid, which was given throughout the treatment period. Tumor response was assessed every 2 months. RESULTS: There were 47 patients (25 women and 22 men) with a median age of 55 years (range 31-79). One hundred seventy four treatments were delivered and were well tolerated. A mean of 2.05 +/- 1.46 (range 0.82-12.8 x 10(9)) cells were infused. Eighty-five percent received two or more doses; 19% received six doses. Objective tumor responses were observed in 1/15 renal cell, 1/13 colorectal, 0/6 breast, 0/5 lung, 0/2 gastric, 0/2 sarcoma, 0/1 pancreas, 0/1 prostate, 0/1 melanoma, and 0/1 eccrine. Forty-three patients have died. Median survival was 8.8 months, 1-year survival 35%, and 2-year survival 15%. CONCLUSION: This complex treatment program was feasible. Infusion of these cells was well tolerated. Some antitumor activity was seen in patients with renal cell cancer and colorectal cancer.

Tumor-infiltrating lymphocytes and interleukin-2: dose and schedules of administration in the treatment of metastatic cancer.

PURPOSE: The potential for therapeutic use of tumor-infiltrating lymphocytes (TIL), as adoptive cellular therapy has been touted for many years with some encouraging reports in patients with metastatic melanoma. MATERIALS AND METHODS: We previously described methodologies for TIL production and phenotypic characterization of TIL generated in our laboratory between 1991 and 1995 in semipermeable bags and between 1996 and 2000 in bioreactors. Patients treated in the earlier era were to have received a hybrid bolus and a 12-hour continuous infusion of interleukin (IL)-2 (total, 48 MIU), while in the latter era 4 days of interferon- alpha preceded the TIL and IL-2; which was given by a hybrid schedule that included bolus and 72- hour continuous IL-2 (total, 96 MIU). There were 55 patients, including 23 patients with melanoma, 9 patients with renal cell carcinoma, and 8 patients with colorectal cancer. There was only 1 objective tumor response, which was noted in a patient with renal cell carcinoma. The 55 patients who received these products were grouped in cohorts by treatment era, quantity of TIL received, amount of IL-2 intended, and different combinations of TIL and IL-2. RESULTS: There was no difference in survival by production method (treatment era), or amount of IL-2 given with TIL, but 33 patients who received an intermediate or higher dose of TIL (mean = 54.4 x 10(9)) had a median survival of 11.8 months, compared to 6.4 months for 22 patients who received 1 low-dose TIL (mean = 6.48 x 10(9)) (p = 0.059, log rank test). The objective response rate in this heterogeneous group of patients was not encouraging. The data suggest there may be a dose/benefit relationship between the total number of TIL infused and survival.

Autologous tumor cell line-derived vaccine for patient-specific treatment of advanced renal cell carcinoma.

AIM: We previously reported the laboratory methodology for producing patient-specific irradiated autologous tumor-cell products derived from short-term cultured tumor cells from resected renal cell carcinoma, and described preliminary clinical results. In this study, we report the final clinical results and efforts to define vaccine potency on the basis of clinical outcome for these 25 patients with advanced renal cell carcinoma. MATERIALS AND METHODS: Approximately 10(8) cells from successful short-term cell lines were irradiated, frozen in aliquots of 10(7) cells, then thawed and administered subcutaneously (s.c.) once a week for 3 weeks, then once a month for 5 months. Patients included 19 men and 6 women, who were 43-82 years of age. Six (6) patients had a large primary lesion, 2 patients had regionally advanced disease, 3 patients had been rendered disease-free by surgical resection of distant metastases, and 14 patients had measurable distant metastatic disease. RESULTS: The vaccines were well tolerated, and no delayed autoimmune effects were documented. Delayed-type hypersensitivity (DTH) tests of irradiated tumor cells were positive in only 1 of 25 patients at week 0, but converted to positive in 6 of 18 patients of DTH-negative patients who were retested at week 4. Objective response rate in patients who had measurable metastatic disease was 0 of 14 patients. With a median follow-up of greater than 7 years from the date of the first DTH test, median survival is 33.4 months, 5-year survival is 43%, and 10 patients are alive 3-12 years later. The 7 DTH+ patients survived a median of 2.5 years, and 3 patients are alive after 3, 4, and 7 years. There was no correlation between the number of irradiated cells or viable irradiated cells injected and tumor DTH reactivity or survival. CONCLUSION: This approach is feasible and the therapy is well tolerated, but clinical benefit was not established in this trial. Any further exploration of this product should be limited to the adjuvant setting in a randomized trial.

Phase I/II trial of autologous tumor cell line-derived vaccines for recurrent or metastatic sarcomas.

AIM: We previously reported the laboratory methodology for producing patient-specific irradiated autologous tumor-cell products derived from short-term cultured tumor cells. We attempted to determine the feasibility, safety, and clinical effects of autologous tumor vaccine-derived sarcomas. PATIENTS AND METHODS: Efforts were made to establish tumor cell lines in tissue culture with expansion to 100 million cells for patients who were candidates for therapy. Cells were irradiated and cryopreserved in aliquots of 10 million cells for subcutaneous (s.c.) injections, once a week for 3 weeks, then once a month for 5 months. RESULTS: Efforts were made to establish short-term tumor cell lines from 86 fresh sarcoma specimens (10 primary, 14 recurrent, and 62 metastatic). Initial growth was successful for 48 patients (56%), and cultures were expanded for 36 patients, with 25 patients treated. There were 23 evaluable patients, including 12 women and 11 men, with a median age of 52 years and a range from 16-79 years. Vaccine therapy was well tolerated. Delayed-type hypersensitivity (DTH) tests to irradiated tumor cells were positive in 0 of 20 patients tested at baseline, but converted to positive after 3 weekly vaccinations in 8 of 16 patients who were retested. Median survival for the 8 DTH converters was 16.6 months versus 8.2 months for the 8 responders whose tumor DTH test remained negative, and 6.0 months for the 7 patients who were not tested. No objective responses were recorded among 12 evaluable patients with measurable disease; 10 patients have survived more than 1 year. CONCLUSIONS: This approach is feasible, well tolerated, and the resulting DTH conversion rate is of interest. Patients with minimal tumor burden would be preferred for further future testing.

Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF: planned interim analysis.

AIM: The aim of this study was to investigate the feasibility, safety, and clinical efficacy of patient-specific dendritic cell vaccines in patients with metastatic melanoma. A planned interim analysis was conducted on the first 20 patients. METHODS: Tumor cell lines were established from metastatic tumor, expanded to 200 million cells, and then incubated with interferon-gamma for patients who were candidates for therapy. Cells were irradiated and cryopreserved. Patients underwent leukapheresis to obtain mononuclear cells that were cultured in the presence of IL-4 and GM-CSF to produce dendritic cells, which were incubated with cryopreserved, irradiated tumor cells, and then stored in aliquots of about 20 million cells for subcutaneous (s.c.) injections with GM-CSF once a week for 3 weeks, then once a month for 5 months. RESULTS: The first 20 eligible patients included 10 men and 10 women, with a median age of 48 years (range, 16-79 years). Three (3) patients had brain metastases, and 13 patients had experienced disease progression after biochemotherapy. At the time of vaccine treatment, 6 patients had evaluable metastatic disease, while 14 patients lacked measurable disease. Vaccine therapy was well tolerated, except for what appeared to be GM-CSF-related allergic reactions in 2 patients. Delayed-type hypersensitivity (DTH) tests to irradiated tumor cells were positive in 0 of 20 patients tested at baseline, but converted to positive in 8 patients (40%). At a median follow-up of 13.8 months, there is a 95% overall survival and a 48% progression-free survival. Four (4) patients have already survived more than 3.0 years since starting the vaccine. CONCLUSION: Based on tolerability, rate of tumor DTH conversion, and encouraging survival, the trial will continue accrual to at least 19 patients with measurable disease and 40 patients who lack measurable disease at the time of treatment.

Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival.

OBJECTIVE: We established short-term cultures of pure tumor cells for use as autologous tumor cell vaccines in an effort to study the effects of patients-specific immunotherapy. PATIENTS AND METHODS: Surgically resected fresh tumor was obtained from patients with metastatic cancer. Successful tumor cell lines (5 x 10(7)) were expanded to 10(8) cells, irradiated, and cryopreserved for clinical use. Following a baseline test of delayed-type hypersensitivity (DTH) to an i.d. injection of 10(6) irradiated autologous tumor cells, patients received 3 weekly s.c. injections of 10(7) cells, had a repeat DTH test at week-4, then received monthly vaccinations for 5 months. A positive DTH test was defined as > or = 10 mm induration; survival was determined from the first DTH test. RESULTS: Short-term cell lines were successfully established for 299/695 patients (43%). Vaccines were prepared for 231 patients, 142 of whom were treated, and 125 had a baseline DTH test recorded. Median follow up at the time of analysis was greater than 5 years. There was no difference in survival for any of the following: gender, age > 50 years, melanoma histology, anergy to common recall antigens or baseline DTH test result. Only 17 patients had a positive DTH at baseline (14%), but DTH converted from negative to positive in 31/80 (39%) of those who were tested, and in 31/108 (29%) of all patients (intent-to-convert analysis). For the 48 patients who were DTH-positive at entry, or converted to DTH-positive, the median survival was 30.5 months and 5-year survival 41% compared to 11.4 months and 9% 5-year survival for 77 patients whose DTH was never positive (P2 = 0.003). However, survival was even better for patients whose DTH test converted to positive compared to patients who were DTH-positive at baseline (median 37.5 vs 11.9 mos, P2 = 0.066). CONCLUSION: This patient-specific, cell culture-derived, autologous tumor cell vaccine induced anti-tumor immune reactivity that was associated with improved survival in patients with advanced cancer.

Radioimmunotherapy for non-Hodgkin's lymphoma with yttrium 90 ibritumomab tiuxetan.

The increasing incidence of non-Hodgkin's lymphoma (NHL), coupled with the lack of optimal treatment options, has prompted the development of novel treatments. Of these, radioimmunotherapy is one of the most promising. Two of the radiolabeled monoclonal antibody therapies being studied in the treatment of NHL are yttrium 90 (90Y) ibritumomab tiuxetan and iodine 131 (131I) tositumomab. The radionuclides 90Y and 131I emit beta radiation; 131I also emits gamma radiation, thus requiring more elaborate precautionary measures to limit radiation exposure. The monoclonal antibody portions of the drugs target the CD20 surface antigen that is present on the majority of B-cell lymphomas, resulting in direct radiation to the targeted cells, as well as indirect targeting of adjacent cells (known as the crossfire effect). Clinical trials of 90Y ibritumomab tiuxetan in patients with NHL have produced promising results. The safe and effective use of radioimmunotherapy requires a multidisciplinary team approach in which nurses play a central role.

Establishing a radioimmunotherapy outpatient care clinic for Non-Hodgkin's lymphoma.

OBJECTIVES: To describe an outpatient treatment model for treating non-Hodgkin's lymphoma with radioimmunotherapy. DATA SOURCES: Experiences of The Hoag Cancer Canter (Newport Beach, CA) in developing an outpatient treatment model. CONCLUSIONS: The Hoag Cancer Center has put an outpatient radioimmunotherapy treatment model into place. Goals include providing coordinated, collaborative care, safe delivery of radioimmunotherapy in an outpatient setting, and establishing an education program for the medical team, patient, and patient's family. IMPLICATIONS FOR NURSING PRACTICE: In providing outpatient treatment for non-Hodgkin's lymphoma, nurses will have many functions, including educating patients and family, coordinating treatment schedules, adhering to radiation safety guidelines, and reviewing post-therapy and long-term side effects that might occur at home.

Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma.

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.

Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific antitumor vaccines in patients with metastatic melanoma: final report.

UNLABELLED: Between January 2001 and September 2007, we treated 54 metastatic melanoma patients with patient-specific tumor cell vaccines consisting of dendritic cells (DCS), derived from their peripheral blood cells that were cultured in interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor (GM-CSF), which had phagocytosed irradiated autologous tumor cells from a continuously proliferating, self-renewing, autologus tumor cell (TC) culture. The loaded DCs were injected subcutaneously in 500 microg of GM-CSF weekly x three, and then monthly for 5 months, for a total of up to 8 injections. The 34 men and 20 women had a median age of 50.5 years; 32 had M1c (visceral metastases and/or elevated lactate dehydrogenase) as their most advanced disease stage. Overall, 83% had received other systemic therapies, including interferon-alpha (n = 20), biochemotherapy (n = 19), GM-CSF (n = 19), chemotherapy (n = 16), IL-2 (n = 13), and other investigational vaccines (n = 7). Patients received an average of 7.4 vaccinations. Treatment was well-tolerated, with most patients experiencing only mild local pruritus and/or erythema. A positive delayed-type hypersensitivity reaction to purified autologous tumor cells was observed at baseline in only 1 of 54 patients, compared to 12 of 54 following vaccination (p = 0.001). The projected 5-year survival rate is an impressive 54% at a median follow-up of 4.5 years (range, 2.4-7.4) for the 30 surviving patients. This survival was superior to that observed following vaccination with irradiated TC in 48 melanoma patients in a previous trial (64 versus 31 months, p = 0.016). This patient-specific vaccine warrants further investigation, based on its safety and encouraging survival rates. ( CLINICAL TRIAL NUMBER: NCI-V01-1646).

Incidencia de la patología genitourinaria en urgencias / Incidence of genitourinary pathology in the emergency department

Objetivo: El aumento de la presión asistencial de los servicios de urgencias hospitalarios obliga a conocer las características de los pacientes y de los procesos por los que acuden. Este estudio es el primero que calcula tiempo de permanencia en urgencias y factores que se relacionan de manera independiente con ingreso hospitalario. Métodos: Estudio descriptivo y retrospectivo de 2.741 pacientes que acudieron a Urgencias por sintomatología genitourinaria en el año 2011. Se examinaron rasgos clínicos y epidemiológicos. Se realizó un análisis multivariable para conocer los factores relacionados con la resolución final de los pacientes, recurrencia en la asistencia a urgencias y tiempo en urgencias. Resultados: La mayoría de pacientes fueron varones (60,3%), con diagnósticos de hematuria, RAO y patología genital. Las mujeres, presentaron pielonefritis, ITU y dolor lumbar de manera más frecuente. Los varones ingresaron en mayor proporción. La edad, el diagnóstico de infección/sepsis o dolor lumbar y un nivel MTS amarillo o naranja, resultaron ser factores independientes de ingreso. Tanto en el estudio univariable como multivariable, la edad mayor de 60 años (311 vs 220 min), los diagnósticos relacionados con ITU y sepsis (300 vs 250 min) y el ingreso hospitalario como resolución final (440 vs 240 min) influyeron de forma significativa en el tiempo de estancia en Urgencias. Conclusiones: La edad > 60 años, el resultado de ingreso y el diagnóstico de infección/sepsis fueron factores independientes de mayor tiempo en Urgencias. La presencia de dolor persistente y de infección/sepsis se comportaron como factores independientes de ingreso

Objective: The increase of healthcare pressure in Emergency Departments compels us to have a better understanding of patients' characteristics and the pathology they consult for. This is the first study that estimates the waiting time in the emergency room and the factors that are independently related with hospital admission. Methods: Descriptive and retrospective study of 2.741 patients who were admitted to the Emergency Department with genitourinary symptoms in 2011. Clinical and epidemiological features were reviewed. A multivariable study was performed to identify the factors related with the final resolution of patients, recurrence in emergency attendance, and waiting time in the emergency room. Results: Most of the patients were male (60.3%), being diagnosed with hematuria, acute urinary retention and genital pathology. Females complained more frequently for pyelonephritis, urinary tract infection and low-back pain. Male were hospitalized in greater proportion. Age, diagnosis of infection/sepsis or low-back pain, and yellow or orange MTS level were independent features for hospital admission. Also, in the univariate and multivariate study, age > 60 years (311 vs 220 min.), UTI/sepsis related diagnoses (300 vs 250 min.), and hospital admission as final resolution (440 vs 240 min.) had a significant influence in the waiting time in the Emergency Department. Conclusions: Age over 60 years, hospital admission as final resolution and infection/sepsis diagnosis were independent features for further waiting time in the Emergency Department. Persistent pain and symptoms of infection/sepsis behaved as independent features for hospital admission

Utilidad de la biopsia fría ureteral durante la cistectomía radical como predictor de riesgo de recidiva: revisión de nuestra serie / Usefulness of cold ureteral biopsy during radical cystectomy as a predictor of recurrence risk: Review of our series

OBJETIVOS: Evaluar la asociación de márgenes positivos en la biopsia intra-operatoria al tiempo de la cistectomía radical (CR) con el riesgo de recidiva en la anastomosis urétero-ileal o a nivel del tracto urinario superior (TUS), y estudiar posibles factores de riesgo preoperatorios asociados con el margen ureteral positivo. MÉTODO: Estudio descriptivo retrospectivo de pacientes tratados mediante CR debido a carcinoma de células transicionales (CCT), a los que se les realizó al tiempo de la CR una biopsia fría del margen ureteral. Se realizó un análisis descriptivo y distribuciones de frecuencias. Se empleó el test de Fisher, se calcularon los valores de sensibilidad (Se) y especificidad (Sp) de la prueba, y se realizó un análisis de supervivencia. RESULTADOS: Se incluyeron 230 pacientes que fueron sometidos a CR. Previamente a la CR se les realizó resección transuretral (RTU) de vejiga y tomografía axial computarizada (TC). El porcentaje de márgenes positivos fue de 4,8% para el uréter derecho y de 4,7% para el izquierdo. Se detectó recidiva en la anastomosis en el 2,6% de los casos. En un 0,8% se encontró recidiva en el TUS (2 casos) a nivel de pelvis renal izquierda (1 caso) y riñón izquierdo (1 caso). En el análisis multivariante, ni la recidiva en la anastomosis (p=1) ni a nivel del TUS (p=1) a lo largo del seguimiento, se asociaron de forma significativa con la presencia de márgenes positivos. De forma secundaria se estudiaron los posibles factores anatomopatológicos preoperatorios asociados con el riesgo de margen positivo, encontrando asociación entre la anatomía patológica (A-P) intraoperatoria del uréter derecho y CIS en la RTU vesical y con tumor del TUS asociado. La reimplantación con margen positivo no se asoció estadísticamente con recidiva en la anastomosis ni con recidiva en el TUS. Hubo relación entre A-P intraoperatoria de ambos uréteres y la definitiva. CONCLUSIONES: En nuestro estudio, la presencia de márgenes ureterales positivos no se asociaron con mayor riesgo de recidiva en la anastomosis o en el TUS. Aunque sigue siendo un tema a debate, una estrategia a seguir puede ser adaptar la biopsia fría ureteral al riesgo individual y realizarla a pacientes con CIS vesical

OBJECTIVES: To evaluate the association of positive margins in the intraoperative biopsy during radical cystectomy (RC) with the risk of recurrence in the uretero-ileal anastomosis or upper urinary tract (UUT), and identify potential risk factors for positive ureteral margins. METHODS: A retrospective, descriptive study was performed in patients treated with radical cystectomy due to transitional cell carcinoma (TCC), who underwent a cold biopsy of the ureteral margin at the time of cystectomy. A descriptive analysis and frequency distribution was performed. Fisher's test was used to calculate sensitivity and specificity and a survival analysis was performed. RESULTS: 230 patients were included. Prior to RC, transurethral resection of the bladder tumor and a CT scan were done. The percentage of positive margins was 4.81% for the right ureter and 4.27% for the left. Recurrence was detected in the anastomosis in 2.64% of the cases. In a 0.88% recurrence was found in the UUT (2 cases) at the level of left renal pelvis (1 case) and left kidney (1 case). In the multivariate analysis, neither recurrence in the anastomosis (p=1) or at the UUT (p=1) level during follow-up were significantly associated with the presence of positive margins. An association was found between the pathological biopsy of the right ureter and carcinoma in situ (CIS) of the bladder wall with UUT involvement. We found only association between the cold biopsy of the left ureter and tumor in left UTT. Reimplantation with positive margins was not statistically associated with neither ureteroileal anastomosis or UTT relapse. A relationship was found between the cold biopsy of both ureters and the definitive pathology. CONCLUSIONS: In our study, the presence of positive ureteral margins was not associated with an increased risk of recurrence in the anastomosis or UUT. Although it remains a topic for debate, a strategy to follow may be to adapt ureteral cold biopsies to individual risk, thus perform it in patients with bladder CIS

Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma.

This study was performed to obtain safety and survival data for patients with histologically confirmed recurrent glioblastoma multiforme (GBM) who received intralesional lymphokine-activated killer (LAK) cells following surgery. LAK cells were generated by incubating peripheral blood mononuclear cells with interleukin-2 for 3 to 5 days in vitro. Forty patients with pathologic confirmation of GBM at surgery had placement of autologous LAK cells into the tumor cavity. The 23 men and 17 women had a median age of 48 years (range 21-76). The median interval from the original diagnosis of glioma to LAK treatment was 10.9 months. Patients received an average of 2.0 +/- 1.0 x 10(9) LAK cells, with viability of 91 +/- 6.8%. Treatment was well tolerated; there was one death within 60 days. At a median follow-up of 2.3 years, median survival post-LAK was 9.0 months; 1-year survival was 34%. Gender, age, location of tumor, LAK cell lytic activity, number of cells implanted, and inclusion of interleukin-2 at cell instillation were not correlated with outcome. Median survival from the date of original diagnosis for 31 patients who had GBM at initial diagnosis was 17.5 months versus 13.6 months for a control group of 41 contemporary GBM patients (p2 = 0.012). This treatment is safe and feasible. The median survival rates are higher than reported in most published series of patients who underwent reoperation for recurrent GBM. A randomized trial would be needed to establish therapeutic benefit.