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.

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.

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.

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).

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.

[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.

[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.

[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.

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.

Visceral leishmaniasis in patients infected with the human immunodeficiency virus.

The experience with 52 episodes of visceral leishmaniasis diagnosed in 43 patients is reported. The most common symptoms were fever (81%), splenomegaly (65%), hepatomegaly (63%), and pancytopenia (73%). In 79% of the patients, CD4+ cell counts were < 100 cells/mm3. Prior or simultaneous diagnosis of AIDS was made in 29 (67%) patients. Diagnosis was considered fortuitous in 19% of the episodes. In 27% of the episodes, the diagnosis was made on the basis of demonstration of parasites outside the reticuloendothelial system, chiefly blood (7 cases) and gastrointestinal mucosa (5 cases). Parasites were frequently observed or cultured from blood (22/37 episodes) or the digestive tract (8/9 episodes). High antimony doses were more effective than low doses in achieving clinical or parasitological cure (rate of cure, 80% vs. 40%, p = 0.11). Severe toxicity was observed in six (11.7%) of the 51 treated episodes. Severe AIDS-related diseases [odds ratio (OR) 10, p < 0.05] and CD4+ counts (OR 12, p < 0.05) were independent factors for early death. Prophylaxis with monthly pentamidine was not useful in reducing relapses of visceral leishmaniasis.

[Quantification of viremia in patients infected with human immunodeficiency virus with different degrees of immunosuppression]. / Cuantificación de la viremia en pacientes infectados por el virus de la inmunodeficiencia humana con diferentes grados de inmunodepresión.

BACKGROUND: Many of the therapeutical decisions related to patients infected with human immunodeficiency virus (HIV) are taken considering the CD4+ lymphocyte count. The recent availability of procedures which quantitate the number of viral particles in peripheral blood has disclosed that viremia degree is the best predictor of HIV disease progression. Nevertheless, the proportion of subjects who despite a normal CD4+ lymphocyte count, have a high viremia and a high risk of short term progression to AIDS is not well known. PATIENTS AND METHODS: Plasma viremia was investigated in 120 adults subjects with a known time of HIV infection. Fifty-two patients had a CD4+ lymphocyte count > 500 x 10(6)/l (CDC group 1), 42 had a number of CD4+ lymphocytes ranging from 200 and 500 x 10(6)/l (CDC group 2), and 26 had a count < 200 x 10(6)/l (CDC group 3). None of the patients was receiving antiretroviral treatment or had intercurrent infections at the time of the study. RESULTS: Mean values of viremia showed an inverse significant relationship with the CD4+ lymphocyte count. In CDC group 1 subjects the distribution of viremia was as follows: low (< 3,000 copies of HIV RNA/ml) in 16 (30.8%), intermediate in 20 (38.4%), and high (> 30,000 copies of HIV RNA/ml) in 16 (30.8%). In eight subjects from CDC group 1, the duration of HIV infection was less than 5 years. In contrast, in patients from CDC group 3, viremia was high in 17 (65.4%), intermediate in 9 (34.6%), and none of them had a low degree viremia. In CDC group 2 patients, viremia was high in 14 (33.3%), intermediate in 20 (47.6%), and low in 8 (19.1%). CONCLUSION: There is an inverse correlation between the viremia degree and the CD4+ lymphocyte count among HIV-positive patients. Nevertheless, there can be a high viremia in absence of low CD4+ lymphocyte count, particularly among subjects with HIV infection for less than 5 years, in whom an early therapeutical intervention might be warranted.

[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.