Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer.

BACKGROUND/AIMS: To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT). MATERIALS/METHODS: Retrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24-36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26-267). RESULTS: Sixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8-8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7-2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6-9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26-12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33-3.79). CONCLUSION: A positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.

Coexistence of marginal zone cutaneous B-cell lymphoma and classic Hodgkin disease: does a biological relationship exist?

The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the same patient, although previously reported, is very unusual. This situation is extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if there is no personal background of cytostatic treatment. We report a 44-year-old man who developed cutaneous nodules over a period of two years. A marginal zone cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.

Quantitative (1) H MR spectroscopic imaging of the prostate gland using LCModel and a dedicated basis-set: correlation with histologic findings.

Proton magnetic resonance spectroscopic imaging ((1) H-MRSI) has been advocated as a valuable tool for prostate cancer diagnosis. However, a barrier to widespread clinical use of this technique is the lack of robust quantification methods that yield reproducible results in an institution-independent manner. The main goal of this study was to develop a standardized and fully automated approach (LCModel-based) for quantitative prostate (1) H-MRSI. To this end, a dedicated basis set was constructed by the combination of simulated (citrate, Cit; choline, Cho, and creatine, CR) and experimentally acquired (spermine, Spm) spectra. The overlapping Spm, Cho, and Cr could be resolved and quantified individually, thus allowing for the independent assessment of glandular (Cit and Spm) and proliferative (Cho) components. Several metabolite ratios were calculated and compared to the histologic findings of prostatectomy specimens from 10 prostate cancer patients with Gleason scores (3 + 3) and (3 + 4). The Cho mole fraction and the Cho/(Cit + Spm) ratio were found to best discriminate between prostate cancer and healthy tissue. The comparison between the quantitative MRSI results and the histologic findings suggests that no correlation exists between the detected metabolic alterations and the Gleason score of low-grade tumors.

Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS. RESULTS: We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences. CONCLUSION: In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.

[Nitrogen losses and nitrogen balance in patients with malignant infarction of the median cerebral artery submitted to moderate hypothermia (32-33 degrees C)]. / Pérdidas de nitrógeno y balance nitrogenado en pacientes con infarto maligno de la arteria cerebral media y sometidos a hipotermia moderada (32-33 degrees C).

OBJECTIVES: Induction of moderate hypothermia in patients with median cerebral artery (MCA) infarction may produce metabolic and nutritional impairments. Currently, we do not know which is the best method to carry out nutritional assessment in this population group. The aim of the present study was to assess the usefulness of nitrogen balance in the follow-up of patients with MCA submitted to moderate hypothermia (32-33 degrees C) by means of intravascular cooling at the Neurocritical Patients Unit at a tertiary hospital. MATERIAL AND METHODS: We designed a retrospective study including patients with MCA infarction of whom we gathered bio-demographical, clinical, hypothermia, and nutritional variables. Similarly, we carried out a prospective follow-up of a patient with MCA infarction and induced hypothermia, gathering the same variables at different time points of his clinical course. RESULTS: Six patients with MCA infarction submitted to moderate hypothermia for a mean duration of 12 days (interval 9-15) were included in the retrospective series. We observed that nitrogen losses (mean 9.9 g) were lower than those previously thought for critical patients during the acute phase. During the prospective follow-up of the patient with malignant infarction of the MCA from day 1 to day 22 after the application of hypothermia, low levels of nitrogen losses were similarly observed during the phase of induced hypothermia, which increased later on when the patient recovered normothermia. The mean nitrogen expenditure during the period of hypothermia was 10.7 g and increased up to 27.3 g during the normothermia period (day 17). CONCLUSIONS: These results suggest that moderate hypothermia-induced metabolic suppression is clinically relevant and thus the determination of nitrogen balance does not seem to be a useful tool in the nutritional followup of this type of patients.

Long-term monitoring programme of polychlorinated dioxins and polychlorinated furans in ambient air of Catalonia, Spain (1994-2015).

Reductions in concentrations of persistent organic pollutants were observed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in a comparison of two consecutive decades ending in December 31, 2015 (n = 413) and compiled from a 48-station long-term air-monitoring network in Catalonia, Spain. Reductions were observed in geometric mean concentration of total PCDD/Fs, decreasing at a rate of 11% yr-1. Results reflect the relative success of improved pollution control measures at industry and traffic locations. At traffic and industrial locations, PCDD/Fs were reduced by around 68% (from 70 to 22 fg I-TEQ/m3) and 66% (from 57 to 19 fg I-TEQ/m3), respectively. The highest concentration of 1196 fg I-TEQ/m3 was observed during the first decade at an industrial location. The highest concentration over the second decade was at a background location during winter (674 fg I-TEQ/m3). Winter observations are generally higher than those recorded in summer, as evident in an 8-year period of moderate PCDD/F levels (<250 fg I-TEQ/m3, n = 143). PCDD/F congener profiles were identified has having less chlorinated PCDD/F, indicating the presence of nearby combustion sources at selected locations. More long-term sampling campaigns, combined with network optimization and integration into a meteorological model, can offer a tool for future PCDD/Fs control measures in not only Catalonia - but also applicable to other areas.

[Gastrointestinal inflammatory fibroid polyps. Clinical characteristics and follow-up in a series of 26 patients]. / Pólipo fibroide inflamatorio gastrointestinal. Características clínicas y seguimiento de una serie de 26 pacientes.

INTRODUCTION: Inflammatory fibroid polyp (IFP) is a protuberant lesion, located near the muscularis mucosae and composed of a proliferation of fusiform cells and conjunctive fibers surrounding capillaries and a variable inflammatory infiltrate. It is believed to be a poorly controlled inflammatory repair response. Our aim was to study the clinical, pathological and follow-up characteristics of a series of patients with IFP. PATIENTS AND METHOD: We studied 26 IFPs from 25 patients (16 women and 9 men) registered between 1985 and 2001 in a specific register of 3 centers in the city of Gerona (Spain). The variables analyzed were age, sex and clinical presentation, IFP localization and size, mucosal characteristics and associated disease, as well as follow-up information. Routine statistical analyses were performed. RESULTS: IFPs were antral in 16 patients, ileal in 7, jejunal in 2 and colonic in the remaining patient. Size determined whether they were symptomatic (35 +/- 13.6 mm) or asymptomatic (8.4 +/- 6.3 mm). Gastric polyps were significantly smaller than intestinal polyps. Symptomatic polyps (5 out of 16 gastric polyps and 9 out of 10 intestinal polyps) predominated in women and occurred at a significantly lower age than asymptomatic polyps (59.2 versus 74.1 years). Most gastric IFPs were associated with chronic atrophic gastritis while only one ileal polyp was associated with Meckels diverticulum. The mean length of follow-up was 60.6 months and, except in one patient who underwent incomplete resection, no recurrences of IFP were observed. CONCLUSION: IFP is a heterogeneous entity, depending on age at presentation, sex, size and location in the digestive tract. IFP does not recur after resection. The association of gastric IFP and chronic atrophic gastritis could suggest a modulatory effect of the mucosa on IFP growth.

Tuberculous meningitis with acellular cerebrospinal fluid in AIDS patients.

OBJECTIVE: To describe the clinical manifestations of tuberculous meningitis in HIV-positive patients with acellular cerebrospinal fluid (CSF). DESIGN: Retrospective analysis of case reports. METHODS: Four HIV-positive patients with acellular CSF and tuberculous meningitis are reported. RESULTS: Clinical presentation did not indicate meningeal infection in three of the four cases, and CSF tests were unusual in all cases. Two patients were diagnosed only after death. CONCLUSIONS: Acellular CSF may obstruct the diagnosis of tuberculous meningitis in AIDS patients.

Pericardial tamponade and coronary sinus thrombosis associated with central venus catheterization.

We report the rare occurrence of fatal cardiac tamponade due to coronary sinus and right atrial thrombosis associated with central venous catheterization. The clinical course was extremely rapid, with death occurring a few minutes after the acute clinical event. Other causes of acute cardiac tamponade were ruled out by the postmortem studies.

Absence of p53 gene mutations in hepatocarcinomas from a Mediterranean area of Spain. A study of 129 archival tumour samples.

The incidence of p53 gene abnormalities in human hepatocellular carcinoma (HCC) varies in different geographical areas, being higher in regions where hepatitis virus infection and dietary exposure to aflatoxin B1 are the most common aetiological agents. These mutations are less frequently encountered in Europe, although some studies have reported p53 protein overexpression in up to 45% of cases analysed. We have analysed 129 tumour samples of primary malignant hepatic neoplasms recovered from paraffin blocks processed in two pathology laboratories in a Mediterranean area of Spain (Valencia and Gerona). Among 14 cases in which p53 immunohistochemistry expression proved positive, 5 stained in more than 50% of the cell nuclei. By PCR-SSCP analysis we could detect the complete sequence from exon 5 through 8 in 70 cases and part of this region in the remaining cases, but no mutations were found. We found no relationship with the clinical stage, tumour stage or clinical outcome. We conclude that p53 gene alterations are not a major event in the malignant transformation of hepatic cells in this region of the Mediterranean. The variable incidence of p53 gene alterations in other geographical areas may reflect a different genetic background for the aetiology of HCC.

AIDS and tuberculosis in Spain. A report of 140 cases.

From January 1984 to October 1990, 140 of 392 (35.7%) patients with the acquired immunodeficiency syndrome (AIDS) were found to have had tuberculosis. One hundred and sixteen were intravenous drug abusers and 16 were homosexual men. Fever, cough, weight loss and generalised lymphadenopathy were common features of their illness. Tuberculin skin tests were negative in 74% and 55% had intraabdominal lymphadenopathy. The chest radiographs showed hilar lymphadenopathy and lower lobe interstitial or alveolar infiltrates, but rarely cavitation. Forty-one of our patients had pulmonary tuberculosis, 38 had extra pulmonary and in 61 it was disseminated. In 80 cases tuberculosis was the presenting feature of AIDS. Tuberculosis usually responded well to chemotherapy.

Dioxin mass balance in a municipal waste incinerator.

A dioxin mass balance in an Spanish municipal waste incinerator (MWI) is presented. Input and output inventories from two sampling collection episodes including the analysis of PCDD/PCDF in urban solid waste (USW), stack gas emissions, fly ash and slag are reported. In one collection the levels of USW were around 8 pg I-TEQ/g and non-thermal destruction was observed overall. In the other collection the levels of USW were higher (around 64 pg I-TEQ/g) and the dioxin balance revealed a thermal destruction. Analysis of the different waste materials (textile, organic, plastic, wood and paper) was performed separately and the textile samples presented the highest levels.

[Progressive deterioration in an elderly patient]. / Deterioro progresivo en paciente anciano.

Vasculitis is diagnosed with increasing frequency in the elderly. We hereby present the case of an 84-year-old male, who had weight loss, low-degree fever, anemia and epigastric pain. After 14 days of study with the tentative diagnosis of digestive neoplasia, a progressive renal insufficiency was detected. This clinical picture was secondary to ANCA-positive vasculitis. The case poses the differential diagnosis of non-oliguric acute renal failure (FRA) in elder people and the systematics of the study of renal insufficiency in individuals with previously unknown renal function. Also, this patient's history emphasizes the importance of acute deterioration of renal function as a guiding symptom for orienting the interpretation of clinical data. In the present case, a diagnostic hypothesis based only in the pursue of an occult digestive tumor misguided the attention from the main cause of the disease.

[Ribavirin treatment in patients with chronic hepatitis C refractory to interferon-alpha]. / Tratamiento con ribavirina en pacientes con hepatitis crónica C refractaria al interferón alfa.

Four patients with chronic hepatitis C who did not respond to treatment with alpha interferon were treated with oral ribavirin at a dose of 1.000-1.200 mg/day for 6 months. A marked, although transitory, decrease was observed in the transaminase values which returned to pre-treatment values on termination of the same. Normal transaminase values were only obtained at some point in the treatment in two patients. Ribavirin was well tolerated with very slight anemia being detected in all the cases. These results, which are superposable to those of other authors who have studied the effects of this antiviral agent in chronic hepatitis C, suggest that ribavirin may play a role in the treatment of this disease. Given the existing data, this role would be one of a drug associated with interferon with which it may have a synergic action rather than as a monotherapy.

[Serum activity of the lactate dehydrogenase enzyme in patients with human immunodeficiency virus infection]. / Actividad sérica de la enzima láctico deshidrogenasa en pacientes con infección por el virus de la inmunodeficiencia humana.

FOUNDATION: Many patients with infection by the HIV show an increase in the levels of the lactodehydrogenase (LCH) enzyme. In most of these cases, such increase has been associated to the presence of pneumonia by Pneumocystis carinii. In order to analyze other possible causes of this increase, we conducted a study in which the clinical, analytical and immunological condition of a group of HIV+ patients with increased levels of LDH was compared to another group whose values were within normal limits. MATERIAL AND METHODS: The clinical records of 200 patients with HIV infection were retrospectively reviewed. The patients were divided into two groups depending if their LDH values were greater than (group A) or lower than (group B) the upper limit considered as normal in our laboratory (230-460 UI/L). Group A included 150 patients and Group B, 50. RESULTS: Both groups were similar with respect to age, sex risk group for HIV infection, hemoglobin level, platelet count and renal function. The number of patients fulfilling AIDS criteria was significantly greater (p < 0.05) among those with LDH above 460 UI/L. Leukocytes and lymphocytes CD4+ values were significantly greater (p < 0.05) among group B. The diseases more frequently diagnosed in group A were: tuberculosis in 41 cases (27%), pneumonia by P. carinii in 31 (21%), bacterial pneumonia in 19 (13%), disseminated disease by cytomegalovirus in 14 (9%) and by Mycobacterium avium in 12 (8%). Among the patients with increased LDH, their levels were similar in the patients with tuberculosis, pneumocystosis and in the patients with AIDS and those which were in the first stages of the HIV infection. CONCLUSION: The increase in LDH among the patients with HIV infection in the era of the prophylaxis against P. carinii must be carefully interpreted. Greater levels of this enzyme are little specific, but have a high sensitivity in the case of tuberculosis and pneumocystosis.

[Efficacy of ritonavir in HIV positive patients pretreated with nucleoside analogues]. / Eficacia del ritonavir en pacientes VIH+ previamente tratados con análogos de nucleósidos.

The virologic and immunologic efficacy of ritonavir, an HIV protease inhibitor, was examined in 14 HIV-infected patients with a mean CD4+ cell count of 183 x 10(6)/l at baseline. All had been exposed to nucleoside analogs for longer than 6 months; and ritonavir was added to previous ongoing antiretroviral drugs. A mean reduction of 1.5 logs was seen in plasma viral load 4 weeks after began ritonavir, and 9 (64.3%) of 14 patients achieved undetectable levels (< 4,000 HIV-RNA copies/ml). A mean increase of 222 x 10(6) cells was observed in the CD4+ count. Nine (64.3%) individuals reported side effects, although they did not force to stop the medication. In conclusion, the addition of ritonavir seem to be a reasonable alternative strategy in patients with advanced HIV disease and heavy previous exposure to nucleoside analogs.

[Combined antiretroviral therapy for prevention of vertical HIV-1 transmission]. / Terapia antirretroviral combinada para la prevención de la transmisión vertical de la infección por el VIH-1.

A 25-year old woman with rapid HIV disease progression had been receiving zidovudine (ZDV) for two years, when she became pregnant. She had a high viral load and carried out zidovudine-resistant viral strains. For these reasons, and with the main objective to maximally reduce viremia, the association of DDI to ZDV was introduced a few weeks before delivery. The virological follow-up for one year has confirmed the lack of HIV infection in the child. Combined antiretroviral therapy during the last weeks of pregnancy might be considered for the prevention of vertical transmission of HIV in cases of high risk of newborn infection, without adding relevant toxicity.

[Neuroendocrine tumor of the submaxillary gland. Apropos of a case]. / Tumor neuroendocrino de glándula submaxilar. A propósito de un caso.

A case is presented of primary neuroendocrine tumour of the submaxillary gland. Study for metastases was negative, but in a few months a pancreatic tumour appeared, and the patient deceased. We make a bibliographical revision of the subject, which shows the rarity of the localization of small cell tumours in this area.

Analytical approach and occurrence for the determination of mass concentration of PCDD/PCDF and dl-PCB in flue gas emissions using long-term sampling devices.

In this work, a reliable methodology for the simultaneous analysis of PCDD/PCDF and dioxin-like PCB (dl-PCB) in flue gas emissions collected using continuous sampling devices is proposed. The analytical scheme followed the minimum requirements described in the EU standard EN-1948:1,2,3,4 according to samples containing large amounts of dioxins and dl-PCBs or samples collected over a long period of time of about 4 weeks. Parameters, such as reproducibility, precision, limits of detection (LOD), limits of quantification (LOQ), extract aliquot size, analytical blanks, extraction efficiency, as well as the amount of internal standards required for an accurate determination, were assessed. The findings demonstrate the suitability of the proposed analytical scheme for the analysis of PCDD/PCDF and PCB in samples collected using long-term sampling devices. The analysis of five different 5% v/v sample aliquots reported %RSD values lower than 10% for all of the 29 congeners at both low and high levels. Similarly, %RSD values were 3.2 and 2.0 for the low level samples and 0.9 and 1.1%RSD for the high level extracts for PCDD/PCDF and dl-PCB, respectively expressed in total TEQ units. Re-extraction provided values less than 3%, expressed in TEQ. Based on blank analyses, LOD values of 100 pg I-TEQ for PCDD/PCDF and 10 pg WHO-TEQ for dl-PCB were achieved when 5% v/v aliquots were analyzed. Finally, the proposed analytical approach was tested with samples from a wide range of combustion processes such as hazardous and municipal waste incinerators, as well as cement kilns (with and without waste co-incineration).

Assessment of polychlorinated dibenzo-p-dioxin and dibenzofuran emissions from a hazardous waste incineration plant using long-term sampling equipment.

The aim of this work is to evaluate the performance of a continuous monitoring system for the analysis of the mass concentration of PCDD/Fs from stationary sources. Data was acquired from a modern, state of the art, hazardous waste thermal treatment plant for a period of more than 2 years using a commercial available continuous monitoring system. The study consisted of a total of 16 samples, collected in periods from 1 week to 2 months resulting in an average of 360 m³ sampled flue gas per sample. The study showed the system was able to confirm that for a period of more than 2 years the plant was complying with the limit of 0.1 ng I-TEQ/Nm(3). In addition, the data showed the typical fingerprint of such installations which is useful for example in impact studies. Long-term samples were compared to five short-term samples (6 h) collected every 6 months during the study period. Principal component analysis was applied to PCDD/Fs obtained data as useful statistical tool to find out trends and similarities between different samples. Improvement in terms of representativeness of data was achieved through continuous assessment since the starts of the project. The obtained data was further used to determine the emission factor for this activity and the total annual PCDD/Fs release to the atmosphere.