Prevalence and characterization of pain in radiation oncology: the PREDORT multicenter cross-sectional study.

BACKGROUND: Pain in cancer patients has enormous impact on their quality-of-life. Radiation therapy (RT) is a cornerstone in cancer treatment. The objective of the PREDORT study is to estimate the prevalence of pain in patients attending at Radiation Oncology (RO) Services. METHODS: A prospective, multicenter study was designed for patients treated at the RO Services of reference hospitals. Patients were seen in their initial Nursing consultation, during which key data was collected, including demographic and comorbidities data, medical history, and oncological and pain characteristics. The study has received approval from the Ethics Committee of Navarra, and all patients signed the Informed Consent. RESULTS: Of the 860 participating patients, 306 reported some type of pain, which implies a prevalence of 35.6%. Of them, 213 identified a cause of oncological origin. The proportion of pain was similar among sexes, but the proportion of non-cancer pain was higher among women (p < 0.05). Regarding pain intensity, the magnitude of breakthrough pain in patients with oncological pain is nearly 1 point greater than in patients with non-oncological pain (7.53 vs 6.81; p = 0.064). Cancer pain is more likely to be limiting of normal life than non-cancer pain (59% versus 38%, p < 0.001). Regarding analgesic treatment, only 60/306 patients (19.6%) were receiving strong opioids. There were 68 patients with pain without any treatment (22.2%). CONCLUSIONS: The prevalence of pain in cancer patients referred to RO services is 35.6%, with the prevalence of exclusively oncological pain being 24.8%. Understanding and addressing oncological pain is essential to provide comprehensive care to patients.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes. METHODS: Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors. RESULTS: On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copies (21% vs. 84%; p < .0002, hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.7-24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5 years (56% vs. 87%; p = .02, HR = 3.6; 95% CI, 1.1-5.7). Mitochondria and mitochondrial cell-cycle proteins were overexpressed in patients with CYP2D6 CNV. CONCLUSIONS: Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5 years among localized ASCC patients treated with 5-fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets for these high-risk patients. PLAIN LANGUAGE SUMMARY: Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s. However, disease-free survival in late staged tumors is between 40% and 70%. The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease-free survival. The analysis of the proteins in these high-risk patients pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets. Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high-risk of relapse that could be redirected to a clinical trial. Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacy.

The Effect of Public Healthcare Expenditure on the Reduction in Mortality Rates Caused by Unhealthy Habits among the Population.

The health systems of developed countries aim to reduce the mortality rates of their populations. To this end, they must fight against the unhealthy habits of citizens, such as smoking, excessive alcohol consumption, and sedentarism, since these result in a large number of deaths each year. Our research aims to analyze whether an increase in health resources influences the number of deaths caused by the unhealthy habits of the population. To achieve this objective, a sample containing key indicators of the Spanish health system was analyzed using the partial least squares structural equation modeling (PLS-SEM) method. The results show how increasing public health spending and, thus, the resources allocated to healthcare can curb the adverse effects of the population's unhealthy habits. These results have important implications for theory and practice, demonstrating the need for adequate investment in the healthcare system to reduce mortality among the population.

SARS-CoV-2 pneumomediastinum. A proposed pneumomediastinum classification

Pneumomediastinum is a rare complication of viral pneumonias. However, as a result of the COVID-19 pandemic, the reports of SARS-CoV-2 related pneumomediastinum have increased. This type of pneumomediastinum is known as "spontaneous" pneumomediastinum. Spontaneous pneumomediastinum is defined as the presence of air in the mediastinal cavity with no apparent cause, but paradoxically, the group termed "spontaneous" is the one with the greatest trigger. Therefore, we believe that the current classification does not coincide with the definition. We present five SARS-CoV-2 pneumomediastinum cases and propose a pneumomediastinum classification. These are the first published reports in our country. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2252).

El neumomediastino es una complicación poco frecuente de las neumonías virales; sin embargo, a raíz de la pandemia de la COVID-19, los informes de casos de neumomediastino por SARS-CoV-2 se han incrementado. A este tipo de neumomediastino se le denomina espontáneo. Se define como neumomediastino espontáneo a la presencia de aire en la cavidad mediastínica sin ninguna causa aparente, pero paradójicamente, el grupo denominado espontáneo es el que tiene mayor causa desencadenante, por lo tanto, creemos que la clasificación actual no es coherente con el significado. Presentamos cinco casos de neumomediastino por SARS-CoV-2 y proponemos una clasificación para el neumomediastino. Estos son los primeros informes publicados en nuestro país. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2252).

Síndrome hemolítico urémico atípico en lactantes con mutaciones genéticas: Reporte de 3 casos / Atypical hemolytic uremic syndrome (aHUS) in infants, with genetic mutations, about three cases

RESUMEN El síndrome hemolítico urémico atípico (SHUa) es una entidad clínica considerada rara; sin embargo, es la causa más común de insuficiencia renal aguda en niños. Esta enfermedad se acompaña de anemia hemolítica microangiopática, trombocitopenia, retención nitrogenada y afectación de la función renal, por lo que representa alta morbilidad y compromiso sistémico. Se reportan tres casos de SHUa en lactantes que presentaron pródromos respiratorios, diarrea, anemia hemolítica y trombocitopenia, con pérdida de función renal. Estos casos mostraron que dicha patología está asociada a mutaciones en los genes: CFH (Complemento Factor H), MCP (Membrana Cofactor Proteín), CFHR1 (Complemento Factor H-Related Proteín1), CFHR5 (Complemento factor H-Related Protein 5) y el gen C3 (Complemento component 3). Los genes CFH y MCP se encontraron afectados en dos de los casos, mientras que el tercer caso mostró una mutación nueva no reportada en el gen C3. Estos resultados evidencian que estas mutaciones están presentes en el Perú, por lo que se debe investigar y establecer medidas de prevención para reducir el alto riesgo de morbilidad y mortalidad que presentan los niños portadores SHUa.

SUMMARY The atypical hemolytic uremic syndrome (aHUS) is a rare clinical entity, but it is the most common cause of acute kidney failure in kids. The disease is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, and it is associated with high morbidity and systemic involvement. We report here three cases of aHUS in infants presenting with prodromal respiratory symptoms, diarrhea, hemolytic anemia, thrombocytopenia and acute renal failure. aHUS cases depict mutations in several genes: membrane cofactor protein (MCP) and complement factor H related proteins 1 and 5 (CFH, RP1 and PR5. Two our patients showed mutations in the genes CFH and MCP, and one presented a new non-previously reported mutation in the gen C3. Our results emphasize the existence of these aHUS mutations and underscore the need to study them to prevent morbidity and mortality.

Pyrazinamide-isoniazid hybrid: synthesis optimisation, characterisation, and antituberculous activity / Híbrido pirazinamida-isoniacida: optimización de síntesis, caracterización y actividad antituberculosa / Híbrido pirazinamida-isoniazida: otimização da síntese, caracterização e atividade antituberculose

Abstract Over time, the effective resistance mechanisms to various first- and second-line drugs against the disease of tuberculosis make its treatment extremely difficult. This work presents a new approach to synthesizing a hybrid of antituberculosis medications: isoniazid (INH) and pyrazinamide (PZA). The synthesis was performed using ultrasound-assisted synthesis to obtain an overall yield of 70%, minimizing the reaction time from 7 to 1 h. The evaluation of the biological activity of the hybrid (compound 2) was tested using the tetrazolium microplate assay (TEMA), showing inhibition in the growth of Mycobacterium tuberculosis H37Rv at a concentration of 0.025 mM at pH 6.0 and 6.7.

Resumen Debido a los grandes mecanismos de resistencia a lo largo del tiempo de diversos fármacos de primera y segunda línea contra la enfermedad de la tuberculosis, el tratamiento sigue dificultándose. Este trabajo presenta un nuevo enfoque para sintetizar un híbrido de fármacos antituberculosos: isoniazida (INH) y pirazinamida (PZA). La síntesis fue asistida por ultrasonido con el fin de obtener un rendimiento global del 70%, minimizando el tiempo de reacción de 7 a ' h. La evaluación de la actividad biológica del híbrido (compuesto 2) se probó usando el ensayo de microplaca de tetrazolio (TEMA), que mostró una inhibición en el crecimiento de Mycobacterium tuberculosis H37Rv a una concentración de 0,025 mM a pH 6,0 y 6,7.

Resumo Devido aos grandes mecanismos de resistência ao longo do tempo a diversos fármacos de primeira e segunda linha contra a tuberculose, o que torna seu tratamento extremamente difícil. Este trabalho apresenta uma nova abordagem para sintetizar um híbrido de fármacos antituberculose: isoniazida (INH) e pirazinamida (PZA) A síntese foi realizada utilizando a síntese assistida por ultrassom de forma a obter um rendimento global de 70%, minimizando o tempo de reação de 7 h para ' h. A avaliação da atividade biológica do híbrido (composto 2) foi testada utilizando o ensaio de microplaca de tetrazólio (TEMA), mostrando uma inibição no crescimento de Mycobacterium tuberculosis H37Rv na concentração de 0,025 mM em pH 6,0 e 6,7.

Understanding colorectal twitter: A comparison of its highest and lowest rank influencers.

The distribution of content related to colorectal surgery in social media is steadily increasing. Social media influencers possess large audiences and are frequently viewed as authority; however, their credibility is often unchecked. In our commentary we present our analysis and comparison of the most and least influential accounts on Twitter within the field of colorectal surgery. Additionally, we discuss the current literature, role and importance of social media for the modern surgeon.

Impact of the COVID-19 pandemic during Spain's state of emergency on the diagnosis of colorectal cancer.

INTRODUCTION: We evaluate the impact of COVID-epidemic in colorectal cancer (CRC) diagnosis during Spain's state of emergency. METHODS: We compared newly diagnosed patients with patients diagnosed in the same period of 2019. RESULTS: A new diagnosis of CRC decreased 48% with a higher rate of patients diagnosed in the emergency setting (12.1% vs. 3.6%; p = .048) and a lower rate diagnosed in the screening program (5.2% vs. 33.3%; p = .000). CONCLUSIONS: Fewer patients have been diagnosed with CRC, with a higher rate of patients diagnosed in an emergency setting.

A Giant Childhood Mesenteric Lipoblastoma With Extensive Maturation.

Abdominal lipoblastomas are uncommon soft tissue tumors in children and rarely arise from the mesentery. Due to intraabdominal location and slow growth, these masses can go unnoticed for long periods of time and often found on surgical exploration. We present a case of a 12-year-old male with years of abdominal distension accompanied by new onset early satiety that was found to have an intra-abdominal mass. He underwent an exploratory laparotomy revealing a large 33 x 27 x 15 cm rubbery mesenteric mass displacing the entire intra-abdominal contents, connected by a single vascular pedicle and encasing a loop of small intestine. The mass was resected and the patient did well without signs of recurrence. Histology confirmed the presence of mature adipocytes but on further cytogenetic analysis, a translocation between chromosomes 2 and 8 at the 12q arm was detected, which is often associated with lipoblastomas. This case represents the one of the largest mesenteric lipoblastomas that matured extensively to lipoma-like histology at the time of surgical resection.

Radiopotentiation of enzalutamide over human prostate cancer cells as assessed by real-time cell monitoring.

AIM: To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells. BACKGROUND: While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. MATERIALS AND METHODS: Here, we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real-time cell analysis (RTCA), androgen-sensitive LNCaP cells (Lymph Node Carcinoma of the Prostate) and androgen-independent PC-3. Both cell lines were highly resistant to high doses of radiotherapy. RESULTS: A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. CONCLUSIONS: These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.

GEORCC recommendations on target volumes in radiotherapy for Head Neck Cancer of Unkown Primary.

Head Neck Cancer of Unknown Primary (HNCUP) is a rare condition, representing approximately 5-10% of all head neck cancers. Radiotherapy, adjuvant or radical, is usually employed in the treatment of those patients. To date, no specific guidelines for the optimal definition of the target volume to be irradiated have been published. In recent years, there have been advances in the knowledge of the molecular biology of HNCUP, its diagnostic imaging and the implementation of sophisticated radiotherapy techniques with enhanced precision in target localization and treatment delivery. These progresses have provided valuable information about the natural history of HNCUP that will allow for establishment of the best treatment for each patient, including standardized, consistent and reproducible target volumes definitions. Several recommendations regarding how to choose volumes when contouring HNCUP in clinical practice are reported, in order to achieve a high rate of loco-regional control while avoiding unnecessary toxicity.

Urological approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a clinical care center.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with significant manipulation of the urinary tract (UT). We aim to describe the urological events and their management in patients who underwent CRS-HIPEC. METHODS: Clinical records of patients who underwent treatment between 2007 and 2015 were reviewed. Urological events and their multidisciplinary management were analyzed. Descriptive statistics were calculated. RESULTS: A total of 103 patients were included. Mean age was 51 years (SD ± 11.8). Mean peritoneal cancer index (PCI) was 20.4 (SD ± 10.1). Primary tumors included appendicular (64%), gynecological (16%), colorectal (10%), and peritoneal mesotheliomas (9%). Ninety-three percent of patients had bilateral ureteral catheters inserted prior to surgery, without complications. Intraoperative UT injuries occurred in 7% of patients. In 5% of patients, tumor invasion of the bladder was evident at surgery and partial resection and primary repair of the bladder wall was performed. Urological complications included urinary tract infection (UTI) (21%) acute post-renal failure (4%), urinary fistulae (4%), and acute urinary retention (AUR) (1%). CONCLUSIONS: In our study, intraoperative UT events and postoperative complications, although not neglectable, were infrequent. Due to the high complexity of these cases, a multidisciplinary approach is mandatory. However, randomized clinical trials are necessary to clarify current data on the need and efficacy of prophylactic ureteral catheterization in patients undergoing CRS-HIPEC.

To What Extent Does Radiotherapy Improve the Quality of Life of Patients With Bone Metastasis?: A Prospective, Single-Institutional Study.

PURPOSE/OBJECTIVES: Radiation therapy (RT) is an effective method of palliating painful bone metastases and improves the quality of life (QoL) of these patients. The purpose of this trial is 2-fold: to quantify the impact of RT in the QoL of patients with bone metastasis and to compare the QoL results between the most used schemes of RT at our Centre. MATERIALS AND METHODS: A consecutive sample of patients with bone metastasis treated with RT in the Complejo Hospitalario de Navarra, Spain, was addressed between January 2011 and November 2012. The QoL was measured with the Quality of Life Questionnaire-C15-Palliative questionnaire, a short version of the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 for palliative care. Two assessments were proposed for each patient: one on the first day of the treatment and the other one a month after the end of the radiotherapy sessions. One hundred and sixteen patients completed the first questionnaire and 75 completed the second one (65%). RESULTS: Significant differences appeared in 9 domains, with better QoL in the second assessment. Five areas (physical functioning, global, fatigue, nausea, dyspnea, and constipation) showed little change (between 5 and 9 points), 3 (emotional functioning, insomnia, and appetite loss) showed moderate change (10 to 20 points), and 1 (pain) showed a very positive change (>30 points).When we compare the QoL scores between the 2 most used schemes of RT (30 Gy/10 fractions vs. 20 Gy/4 to 5 fractions), there are no significant differences in any QoL areas (and in 2 areas P was near 0.05). CONCLUSIONS: Palliative RT is a very active treatment for patients with bone metastasis regardless of age, location, primary tumor, or RT scheme. RT significantly improves the QoL, fundamentally by controlling pain and reducing analgesic use. Shorter schemes of RT produce at least-if not better-the same effect on QL than longer schemes (30 Gy).

Current Status of Radiotherapy for the Management of Regional Nodes in Breast Cancer.

Worldwide, breast cancer is the most common invasive cancer in women. Breast cancer constitutes about 23% of invasive cancers in women. The management of breast cancer depends on various factors, including the cancer stage and patient age. Breast cancer is usually treated with surgery, which can be followed by chemotherapy or radiation therapy, or both. Until recently, the standard procedure for axillary study was axillary dissection. Sentinel lymph node biopsy has been validated as a less-aggressive axillary treatment without an impact on survival. In the present report, we review the current management of the axillary lymph nodes, especially from the viewpoint of an oncology radiotherapist.

Contrast-enhanced ultrasound (CEUS): an excellent tool in the follow-up of small renal masses treated with cryoablation.

Strict imaging follow-up is mandatory after cryoablation of small renal masses (SRMs). Although it uses ionizing radiation and nephrotoxic iodinated contrast, computed tomography (CT) is still the gold standard test. Contrast-enhanced ultrasound (CEUS) is a novel technique that informs in real time about renal perfusion avoiding radiation and nephrotoxicity. The objective of this study is to compare outcomes between CEUS and CT in the follow-up of SRMs treated with cryoablation, as well as to assess degree of agreement between them. This is a prospective observational study (May 2012 to December 2013) comparing CEUS and CT in 16 patients with SRMs cryoablated. The on-going protocol of the study includes a CT and CEUS 3 months after treatment and then every 6 months during 5 years. Local relapse was defined as the presence of contrast enhancement in the mass. All the CEUS were performed by a single experienced observer (E.S.). Degree of agreement was measured with kappa index. CEUS detected contrast enhancement in three patients (3/16, 18.8%) and CT in two patients (2/16, 12.5%). Degree of agreement between CEUS and CT, according to Landis-Koch classification, was 0.76 (CI 0.33-1.19; p = 0.0165), which is excellent and higher than expected by random. Sensitivity of the test is 93.75% (15/16). Median time of follow-up after cryoablation is 22 months (15.5-36.5). CEUS has an excellent agreement with CT and a high sensitivity in the follow-up of SRMs treated with cryosurgery, demonstrating its usefulness. Due to these encouraging results, it could become a reference test in the near future for monitoring SRMs after ablative treatment.