Un reto multidisciplinar: tratamiento con fósforo-32 en el carcinoma de páncreas localmente avanzado / A multidisciplinary challenge: Therapy with phosphorus-32 for locally advanced pancreatic cancer

El cáncer de páncreas es una enfermedad de pronóstico precario, siendo su supervivencia global la que menos ha mejorado en los últimos 40 años entre todos los cánceres. El adenocarcinoma de páncreas localmente avanzado, sin metástasis a distancia, pero con una afectación vascular limitante, constituye casi un tercio de estos pacientes. En este grupo se concentran gran parte de los esfuerzos investigadores para introducir tratamientos que permitan un aumento de las tasas de rescate quirúrgico y/o de la supervivencia, con 2 objetivos fundamentales: el del control local y el de la prevención de la progresión sistémica. El tratamiento intratumoral con micropartículas de fósforo-32, guiado por ecoendoscopia y combinado con quimioterapia estándar puede tener beneficios significativos y clínicamente relevantes en estos pacientes y, por tanto, una opción valiosa de tratamiento en una enfermedad en la que existe una necesidad urgente de desarrollar nuevas terapias que nos ayuden a mejorar los resultados (AU)

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes (AU)

A multidisciplinary challenge: Therapy with phosphorus-32 for locally advanced pancreatic cancer.

Pancreatic cancer is a disease with a poor prognosis, and overall survival has improved the least in the last 40 years of all cancers. Locally advanced pancreatic adenocarcinoma, without distant metastasis but with limiting vascular involvement, constitutes almost one third of these patients. This group is the focus of most research efforts to introduce treatments to increase surgical salvage rates and/or survival, with two main objectives: local control and prevention of systemic progression. Intratumoural treatment with phosphorus-32 microparticles, guided by echoendoscopy and combined with standard chemotherapy may have significant and clinically relevant benefits in these patients, and therefore a valuable treatment option in a disease where there is an urgent need to develop new therapies to help improve outcomes.

Spectroelectrochemical Studies of CTAB Adsorbed on Gold Surfaces in Perchloric Acid.

The behaviour of CTAB adsorbed on polycrystalline gold electrodes has been studied using a combination of spectroelectrochemical methods. The results indicate that the formation of the layer is the consequence of the precipitation of the CTAB micelles on the electrode surface as bromide ions, which stabilize the micelles, are replaced by perchlorate anions. This process leads to the formation of CTA+ layers in which perchlorate ions are intercalated, in which the adlayer suffers a continuous rearrangement that leads to the formation of micro-dominions of different types of hydrogen-bonded water populations throughout the adlayer. After prolonged cycling, a stable situation is reached. Under these conditions, water molecules permeate through the adlayer toward the electrode surface at potentials positive of the potential of zero charge, due to the repulsion between the CTA+ layer and the positive charge of the electrode.

First wave of COVID-19 impact on emergency general surgery in a Spanish tertiary hospital. A cohort study.

INTRODUCTION: The need to care for patients with emergency symptoms still continues during the COVID-19 pandemic. The number of emergency surgery procedures performed in Spanish hospitals decreased significantly during the first wave of COVID-19. PATIENTS AND METHODS: We performed a retrospective cohort study comparing the emergency surgery activity in a Spanish tertiary Hospital during the COVID-19 pandemic and emergency surgery activity registered in 2019 during the equivalent time period. RESULTS: A total of 1802 patients were included in control group (CG) versus 756 in pandemic group (PG). Mean number of patients who underwent emergency surgery during the control and pandemic periods was 3.42 patients per day, in contrast to 1.62 during the pandemic period, which represents a 52.6% decrease in emergency surgery activity. During the pandemic period, most of the patients consulted after more than 72 h of symptoms, representing a delay in presenting in the ER of 23.7% when compared to CG. Surgeries due to complications from previous elective procedures decreased (12% vs. 6.1%) in PG, probably because elective procedures are being postponed. We had a 13.1% COVID-19 positivity rate. Morbidity was higher during pandemic (52.5% vs. 35.2%). Mortality rates in patients undergoing emergency surgery was higher in PG (12.1% vs. 4.8%). CONCLUSIONS: The impact of the first wave of COVID-19 in emergency surgery activity has been profound. A significant reduction in emergency surgery was observed, along with longer time periods between patients' onset of symptoms and their arrival at the Emergency Department. Higher morbidity was also observed during the pandemic period.

Usefulness of histological superstudy of sentinel lymph nodes detected with radioisotopes in colon cancer.

INTRODUCTION: Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer (CC) and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20%-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. MATERIAL AND METHODS: Prospective study of a series of patients who have undergone curative surgery for CC, to whom we perform selective biopsy of sentinel node (SBDN). Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (Hematoxilin-Eosin stain (H-E) in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with H-E in serial sections, immunohistochemistry (IHC) and molecular study with OSNA® (One Step Nucleic Acid Amplification). Diagnostic validity study od SBSN was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. RESULTS: We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/patient), from which 145 are SN (2,34 SN/patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9+ LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (P < .001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. CONCLUSION: Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in CC, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.

KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor.

BACKGROUND: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.

Usefulness of histological superstudy of sentinel node detected with radioisotope in colon cancer. / Utilidad del superestudio anatomopatológico de ganglio centinela detectado con radioisótopos en el cáncer de colon.

INTRODUCTION: Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN. MATERIAL AND METHODS: Prospective study of a series of patients who have undergone curative surgery for colon cancer, to whom we perform selective biopsy of sentinel node. Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (hematoxilin-eosin stain in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with hematoxilin-eosin in serial sections, immunohistochemistry (IHC) and molecular study with One Step Nucleic Acid Amplification (OSNA®). Diagnostic validity study od selective biopsy of sentinel node was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN. RESULTS: We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/ patient), from which 145 are SN (2,34 SN/ patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9 +LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (p<.001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a. CONCLUSION: Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in colon cancer, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

Toxicity and inhibition assessment of ionic liquids by activated sludge.

Toxicity of 13 ionic liquids (ILs) corresponding to different families were studied by inhibition respiration assays (15 min) using activated sludge. Toxicity increased as increasing the number of carbons in the alkyl-chain of imidazolium-based ILs, with EC50 values from 4.19 to 0.17 for 1-ethyl-3-methylimidazolium chloride ([Emim][Cl]) and 1-octyl-3-methylimidazolium chloride ([Omim][Cl]), respectively. An increase in toxicity was observed for aromatic-based ILs (pyridinium- and imidazolium-based ILs) due to the hydrophobic character of the head groups in comparison with linear structures as phosphonium and ammonium cations. Among to the anions studied fixing [Emim]+ as cation, [HSO4]- and [NTf2]- presented low EC50 values (0.34 mM and 1.69 mM, respectively) while [Cl]- and [EtSO4]- were considered harmless anions due to the hydrophilic character of chloride and the organic nature of [EtSO4]-. ILs toxicity/inhibition was determined by adding a biodegradable compound and measuring the sludge response after being in contact with the ILs for at least 15 h. The exposure of sewage sludge to ILs for more than 15 min used in short inhibition assays caused more toxic effect on microorganisms, even for [Choline][NTf2], previously defined as practically harmless (EC50 = 2.79 mM). Biodegradability assays confirmed the biodegradable nature of choline cation, related with TOC conversion of 40%, only due to cation consumption. No oxygen consumption or even lysis of microbial cells was observed for Tetrabutylammonium bis(trifluoromethylsulfonyl)imide and for 1-Ethyl-3-methylimidazolium hydrogensulphate due to the presence of anions previously defined as hazardous ([NTf2]- and [HSO4]-), maintaining their recalcitrant character to sewage systems.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

Análisis del escenario microscópico de una biopsia prostática negativa como predictor del riesgo de cáncer de próstata. Una revisión sistemática / In Search for risk predictors at the microscopic scenario of a negative biopsy. A systematic review

Introducción: Las biopsias prostáticas (BP) de repetición, ante la persistencia de la sospecha de cáncer de próstata (CP), son frecuentes y su rendimiento bajo. En el contexto de una BP negativa existe un escenario microscópico (EM), que definimos como el conjunto de lesiones no neoplásicas identificable. La existencia de algunas de estas lesiones incrementa el riesgo de detección de CP en BP sucesivas, mientras que otras parecen tener un efecto protector. El objetivo de esta revisión sistemática es identificar el conjunto de lesiones que puede formar parte del EM de una BP negativa y analizar la evidencia actual de su asociación con el riesgo de detección de CP en BP sucesivas. Adquisición de la evidencia: Dos revisores independientes realizaron una búsqueda bibliográfica en Medline, Embase y Central Cochrane, con los términos de búsqueda: small acinar proliferation or ASAP or prostatic intraepithelial neoplasia or HGPIN or adjacent small atypical glands or pinatyp or atrophy or proliferative inflammatory atrophy or pia or prostatic inflammation or prostatitis and prostate cancer. Se identificaron 1.015 referencias y siguiendo los principios de la declaración PRISMA y de selección PICO, se identificaron 57 artículos originales válidos para esta revisión. Síntesis de la evidencia: La proliferación acinar atípica de célula pequeña se asocia a una tasa de detección de CP en BP sucesivas que oscila entre el 32 y 48%. La neoplasia intraepitelial prostática de alto grado (HGPIN) se asocia a CP entre el 13 y 42%, siendo su multifocalidad la que define el incremento en el riesgo de detección. La atrofia prostática, la atrofia proliferativa inflamatoria y la infamación prostática parecen tener un efecto protector sobre la detección de CP en BP sucesivas. Por otra parte, el riesgo de detección de CP en varones con HGPIN multifocal se reduce significativamente si coexiste atrofia proliferativa inflamatoria. Conclusiones: El EM de una BP negativa puede estar compuesto por las lesiones de proliferación acinar atípica de célula pequeña, HGPIN, atrofia prostática, atrofia proliferativa inflamatoria e infamación prostática ya que todas parecen estar asociadas al riesgo de detección de CP en BP sucesivas. Esta revisión nos permite generar la hipótesis de que el EM de una BP negativa puede ser de utilidad en la decisión indicar BP de repetición

Introduction: In cases of persistent suspicion of prostate cancer (PC), repeat prostate biopsies (PB) are frequently performed in spite of their low yield. In the context of a negative PB, there is a microscopic scenario (MS), which we define as the group of recognizable non-neoplastic lesions. While some of these lesions seem to have a protective effect, the existence of others increases the risk of PC detection in posterior PB. The objective of this systematic review is to identify the lesions that may belong to the MS of a negative PB and analyse the current evidence of their association with the risk of detecting PC in subsequent PBs. Evidence acquisition: Two independent reviewers conducted a literature search on Medline, Embase and Central Cochrane with the following search terms: small acinar proliferation, ASAP, prostatic intraepithelial neoplasia, HGPIN, adjacent small atypical glands, pinatyp, atrophy, proliferative inflammatory atrophy, pia, prostatic inflammation, prostatitis and prostate cancer. 1,015 references were first identified, and 57 original articles were included in the study, following the PRISMA declaration and the PICO selection principles. Evidence synthesis: Atypical small acinar proliferation is associated with PC detection in repeat PB with rates ranging between 32 and 48%. High-grade prostatic intraepithelial neoplasia (HGPIN) is related to PC in 13 to 42% of cases. Studies show that HGPIN, when multifocal, is a significant independent risk factor for PC. Prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation seem to act as protective factors on the detection of PC in repeat PB. On the other hand, the risk of PC detection reduces significantly in male patients with multifocal HGPIN and coexistent PIA. Conclusions: The MS of a negative PB may include atypical small acinar proliferation, HGPIN, prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation lesions, since they all seem to be associated with the risk of PC detection in repeat PB. This review has led us to create the hypothesis that the MS of a negative PB might be a valuable and useful tool when considering repeat PB

Benthic marine litter in shallow fishing grounds in the NW Mediterranean Sea.

Fisheries are one of the main economic sectors affected by marine litter, which can damage gear, reduce catch, and require time to repair or clean nets. This study aims to evaluate the type and density of marine litter in two shallow fishing grounds in the NW Mediterranean Sea, both belonging to the Natura 2000 network. Moreover, it quantifies the fraction of marine litter within the total catch to help understand the potential influence of marine litter on fisheries. Two study areas were selected, one in the vicinity of urban populated areas and high navigational traffic and one in a rural site off an agricultural area. The urban area had more benthic marine litter (393 to 198 kg km-2) including clinker (residue from coal-burning steamships), fabric, plastics, and processed wood and accounting for up to 38% of the total catch. The rural area had far less marine litter (34-56 kg km-2), accounting for only 5% of the total catch. Marine litter may have potential negative effects on fisheries; thus we propose that government credit trading programs could be promoted to help recover litter from fishing catches, to reduce fishing costs and hazards to marine ecosystems.

In Search for risk predictors at the microscopic scenario of a negative biopsy. A systematic review. / Análisis del escenario microscópico de una biopsia prostática negativa como predictor del riesgo de cáncer de próstata. Una revisión sistemática.

INTRODUCTION: In cases of persistent suspicion of prostate cancer (PC), repeat prostate biopsies (PB) are frequently performed in spite of their low yield. In the context of a negative PB, there is a microscopic scenario (MS), which we define as the group of recognizable non-neoplastic lesions. While some of these lesions seem to have a protective effect, the existence of others increases the risk of PC detection in posterior PB. The objective of this systematic review is to identify the lesions that may belong to the MS of a negative PB and analyse the current evidence of their association with the risk of detecting PC in subsequent PBs. EVIDENCE ACQUISITION: Two independent reviewers conducted a literature search on Medline, Embase and Central Cochrane with the following search terms: small acinar proliferation, ASAP, prostatic intraepithelial neoplasia, HGPIN, adjacent small atypical glands, pinatyp, atrophy, proliferative inflammatory atrophy, pia, prostatic inflammation, prostatitis and prostate cancer. 1,015 references were first identified, and 57 original articles were included in the study, following the PRISMA declaration and the PICO selection principles. EVIDENCE SYNTHESIS: Atypical small acinar proliferation is associated with PC detection in repeat PB with rates ranging between 32 and 48%. High-grade prostatic intraepithelial neoplasia (HGPIN) is related to PC in 13 to 42% of cases. Studies show that HGPIN, when multifocal, is a significant independent risk factor for PC. Prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation seem to act as protective factors on the detection of PC in repeat PB. On the other hand, the risk of PC detection reduces significantly in male patients with multifocal HGPIN and coexistent PIA. CONCLUSIONS: The MS of a negative PB may include atypical small acinar proliferation, HGPIN, prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation lesions, since they all seem to be associated with the risk of PC detection in repeat PB. This review has led us to create the hypothesis that the MS of a negative PB might be a valuable and useful tool when considering repeat PB.