Dual-energy CT in the differentiation between adrenal adenomas and metastases: Usefulness of material density maps and monochromatic images.

OBJECTIVE: To evaluate the behavior of adrenal adenomas and metastases with dual-energy CT, analyzing the attenuation coefficient in monochromatic images at three different levels of energy (45, 70, and 140 keV) and the tissue concentrations of fat, water, and iodine in material density maps, with the aim of establishing optimal cutoffs for differentiating between these lesions and comparing our results against published evidence. MATERIALS AND METHODS: This retrospective case-control study included oncologic patients diagnosed with adrenal metastases in the 6-12 months prior to the study who were followed up in our hospital between January and June 2020. For each case (patient with metastases) included in the study, we selected a control (patient with an adrenal adenoma) with a nodule of similar size. All patients were studied with a rapid-kilovoltage-switching dual-energy CT scanner, using a biphasic acquisition protocol. We analyzed the concentration of iodine in paired water-iodine images, the concentration of fat in the paired water-fat images, and the concentration of water in the paired iodine-water and fat-water images, in both the arterial and portal phases. We also analyzed the attenuation coefficient in monochromatic images (at 55, 70, and 140 keV) in the arterial and portal phases. RESULTS: In the monochromatic images, in both the arterial and portal phases, the attenuation coefficient at all energy levels was significantly higher in the group of patients with metastases than in the group of patients with adenomas. This enabled us to calculate the optimal cutoffs for classifying lesions as adenomas or metastases, except for the arterial phase at 55 KeV, where the area under the receiver operating characteristic curve (AUC) for the estimated threshold (0.68) was not considered accurate enough to classify the lesions. For the arterial phase at 70 keV, the AUC was 0.76 (95% CI: 0.663‒0.899); the optimal cutoff (42.4 HU) yielded 92% sensitivity and 60% specificity. For the arterial phase at 140 keV, the AUC was 0.94 (95% CI: 0.894‒0.999); the optimal cutoff (18.9 HU) yielded 88% sensitivity and 94% specificity). For the portal phase at 55 keV, the AUC was 0.76 (95% CI: 0.663‒0.899); the optimal cutoff (95.4 HU) yielded 68% sensitivity and 84% specificity. For the portal phase at 70 keV, the AUC was 0.82 (95% CI: 0.757‒0.955); the optimal cutoff (58.4 HU) yielded 80% sensitivity and 84% specificity. For the portal phase at 140 keV, the AUC was 0.9 (95% CI: 0.834‒0.987); the optimal cutoff (16.35 HU) yielded 96% sensitivity and 84% specificity. In the material density maps, in the arterial phase, significant differences were found only for the iodine-water pair, where the concentration of water was higher in the group with metastases (1018.8 ±â€¯7.6 mg/cm3 vs. 998.6 ±â€¯8.0 mg/cm3 for the group with adenomas, p < 0.001). The AUC was 0.97 (95% CI: 0.893‒0.999); the optimal cutoff (1012.5 mg/cm3) yielded 88% sensitivity and 96% specificity. The iodine-water pair was also significantly higher in metastases (1019.7 ±â€¯12.1 mg/cm3 vs. 998.5 ±â€¯9.1 mg/cm3 in adenomas, p < 0.001). The AUC was 0.926 (95% CI: 0.807‒0.977); the optimal cutoff (1009.5 mg/cm3) yielded 92% sensitivity and 92% specificity. Although significant results were also observed for the fat-water pair in the portal phase, the AUC was insufficient to enable a sufficiently accurate cutoff for classifying the lesions. No significant differences were found in the fat-water maps or iodine-water maps in the arterial or portal phase or in the water-fat map in the arterial phase. CONCLUSIONS: Monochromatic images show differences between the behavior of adrenal adenomas and metastases in oncologic patients studied with intravenous-contrast-enhanced CT, where the group of metastases had higher attenuation than the group of adenomas in both the arterial and portal phases; this pattern is in line with the evidence published for adenomas. Nevertheless, to our knowledge, no other publications report cutoffs for this kind of differentiation in contrast-enhanced monochromatic images obtained in rapid-kilovoltage-switching dual-energy CT scanners, and this is the first new contribution of our study. Regarding the material density maps, our results suggest that the water-iodine pair is a good tool for differentiating between adrenal adenomas and metastases, in both the arterial and portal phases. We propose cutoffs for differentiating these lesions, although to our knowledge no cutoffs have been proposed for portal-phase contrast-enhanced images obtained with rapid-kilovoltage-switching dual-energy CT scanners.

Diatom-Based Nanomedicine for Colorectal Cancer Treatment: New Approaches for Old Challenges.

Colorectal cancer is among the most prevalent and lethal cancers globally. To address this emergency, countries have developed diffuse screening programs and innovative surgical techniques with a consequent decrease in mortality rates in non-metastatic patients. However, five years after diagnosis, metastatic CRC is still characterized by less than 20% survival. Most patients with metastatic CRC cannot be surgically treated. For them, the only option is treatment with conventional chemotherapies, which cause harmful side effects in normal tissues. In this context, nanomedicine can help traditional medicine overcome its limits. Diatomite nanoparticles (DNPs) are innovative nano-based drug delivery systems derived from the powder of diatom shells. Diatomite is a porous biosilica largely found in many areas of the world and approved by the Food and Drug Administration (FDA) for pharmaceutical and animal feed formulations. Diatomite nanoparticles with a size between 300 and 400 nm were shown to be biocompatible nanocarriers capable of delivering chemotherapeutic agents against specific targets while reducing off-target effects. This review discusses the treatment of colorectal cancer with conventional methods, highlighting the drawbacks of standard medicine and exploring innovative options based on the use of diatomite-based drug delivery systems. Three targeted treatments are considered: anti-angiogenetic drugs, antimetastatic drugs, and immune checkpoint inhibitors.

Laser Interstitial Thermal Therapy for the Treatment of Primary and Metastatic Brain Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors that are challenging to treat via traditional methods; however, its safety and efficacy are not yet well validated in the literature. The objectives of the study were to assess the available evidence of the indications and adverse events (AEs) of LITT and 1-year progression-free survival and 1-year overall survival in the treatment of primary and secondary brain tumors. METHODS: A comprehensive literature search was conducted through the databases PubMed, Embase, and the Cochrane Library until October 2021. Comparative and descriptive studies, except for case reports, were included in the meta-analysis. Separate analyses by tumor type (high-grade gliomas, including World Health Organization grade 4 astrocytomas [which include glioblastomas] as a specific subgroup; low-grade gliomas; and brain metastases) were conducted. Pooled effect sizes and their 95% confidence intervals (CI) were generated via random-effects models. RESULTS: Forty-five studies met the inclusion criteria, yielding 826 patients for meta-analysis. There were 829 lesions in total, of which 361 were classified as high-grade gliomas, 116 as low-grade gliomas, 337 as metastatic brain tumors, and 15 as nonglial tumors. Indications for offering LITT included deep/inaccessible tumor (12 studies), salvage therapy after failed radiosurgery (9), failures of ≥2 treatment options (3), in pediatric patients (4), patient preference (1); indications were nonspecific in 12 studies. Pooled incidence of all (minor or major) procedure-related AEs was 30% (95% CI, 27%-40%) for all tumors. Pooled incidence of neurologic deficits (minor or major) was 16% (12%-22%); postprocedural edema 14% (8%-22%); seizure 6% (4%-9%); hematoma 20% (14%-29%); deep vein thrombosis 19% (11%-30%); hydrocephalus 8% (5%-12%); and wound infection 5% (3%-7%). One-year progression-free survival was 18.6% (11.3%-29.0%) in high-grade gliomas, 16.9% (11.6%-24.0%) among the grade 4 astrocytomas; and 51.2% (36.7%-65.5%) in brain metastases. One-year overall survival was 43.0% (36.0%-50.0%) in high-grade glioma, 45.9% (95% CI, 37.9%-54%) in grade 4 astrocytomas; 93.0% (42.3%-100%) in low-grade gliomas, and 56.3% (47.0%-65.3%) in brain metastases. CONCLUSIONS: New neurologic deficits and postprocedural edema were the most reported AEs after LITT, albeit mostly transient. This meta-analysis provides the best statistical estimates of progression and survival outcomes based on the available information. LITT is generally a safe procedure for selected patients, and future well-designed comparative studies on its outcomes versus the current standard of care should be performed.

Espiritualidade e dor em pacientes com câncer de mama metastático / Spirituality and pain in patients with metastatic breast cancer / Espiritualidad y dolor en pacientes con cáncer de mama metastásico

Resumo Mediante estudo observacional, transversal e quantitativo que utilizou os instrumentos de avaliação Brief Pain Inventory (dor), Functional Assessment of Chronic Illness Therapy Spiritual Well-Being (bem-estar espiritual) e Beck Depression Inventory - Short Form (depressão), busca-se avaliar a influência da espiritualidade e da depressão na percepção de dor de pacientes acometidas por neoplasia de mama metastática. A idade média foi 57,3 anos e, das 30 participantes, 24 (80%) tratavam-se em serviço público; 17 (57%) tinham diagnóstico de câncer de mama há mais de cinco anos; e 27 (90%) realizavam alguma prática religiosa/espiritual. Pacientes com escore de bem-estar espiritual acima da mediana apresentaram menor escore dos sintomas depressivos (3 vs . 6; p =0,021). Não houve diferença significativa em relação à mediana do escore total do bem-estar espiritual quando estratificado pela mediana da percepção de dor (31,5% vs . 28,5%; p =0,405). Maior manifestação de bem-estar espiritual pode estar relacionada a menores índices de depressão.

Abstract This observational, cross-sectional and quantitative study, by means of the assessment instruments Brief Pain Inventory, Functional Assessment of Chronic Illness Therapy Spiritual Well-Being and Beck Depression Inventory - Short Form, evaluated the influence of spirituality and depression in the pain perception of patients with metastatic breast cancer. Mean age was 57.3 years. Of the 30 participants, 24 (80%) were treated in a public service, 17 (57%) had been diagnosed with breast cancer for more than 5 years, and 27 (90%) were religious or spiritual. Patients with spiritual well-being scores above the median had lower depressive symptom scores (3 vs. 6; p =0.021). The median total score of spiritual well-being showed no significant difference when stratified by median pain perception (31.5% vs. 28.5%; p =0.405). Greater spiritual well-being may be related to lower rates of depression.

Resumen Este estudio observacional, transversal y cuantitativo utilizó los instrumentos Brief Pain Inventory (dolor), Functional Assessment of Chronic Illness Therapy Spiritual Well-Being (bienestar espiritual) y Beck Depression Inventory - Short Form (depresión), para evaluar si la espiritualidad y la depresión influencian en la percepción del dolor en pacientes con cáncer de mama metastásico. La edad promedio fue de 57,3 años; de las 30 participantes, 24 (80%) recibían atención pública; 17 (57%) tenían diagnóstico de cáncer de mama hace más de cinco años; y 27 (90%) solían tener alguna práctica religiosa/espiritual. Aquellas con puntuación de bienestar espiritual superior a la mediana tuvieron una puntuación más baja de síntomas depresivos (3 vs. 6; p =0,021). No hubo diferencias significativas en la mediana de la puntuación total de bienestar espiritual cuando se estratificó por la percepción mediana del dolor (31,5% vs. 28,5%; p =0,405). Una mayor sensación de bienestar espiritual se relacionó a bajas tasas de depresión.

Effect of Yin Yang protein 1 transcriptionally regulating acetyl-CoA carboxylase 1 on the cell migration and lipogenesis in ovarian cancer / 肿瘤研究与临床

Objective:To investigate the expression of acetyl-CoA carboxylase 1 (ACC1) in ovarian cancer tissues and cells, and the related mechanisms of the effect of ACC1 on cell migration and lipogenesis in ovarian cancer.Methods:Samples including 1 case of normal ovarian tissue, 1 case of ovarian cancer primary lesion tissue and 1 case of ovarian cancer omentum metastatic tissue diagnosed by pathology examination of patients undergoing surgery resection who admitted to Linyi Cancer Hospital between January 2019 and December 2021 were collected. Immunohistochemistry was used to detect the protein levels of ACC1 and Yin Yang protein 1 (YY1) of all tissues. The PROMO database was used to predict the possible binding sites of YY1 and ACC1 promoter region. Through the assembled viral vector, the HEY cells of human ovarian cancer with ACC1 or YY1 expression [the untreated cells were treated as the negative control (NC)], or knocked down ACC1 or YY1 (the interference sequence sh1, sh2, sh3 was transferred to the target gene, and the negative control sequence shNC was transferred to the interference sequence). Double luciferase reporter gene assay was used to verify the binding sites of YY1 and ACC1 promoter and the activity of transcriptional regulation. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of ACC1 and YY1 in the treated HEY cells, respectively. Transwell assay was used to detect the migration ability of HEY cells. Oil red O staining and Nile red staining were used to detect the lipid droplets in HEY cells.Results:The immunohistochemical scores of ACC1 and YY1 were 0, 2, 8 scores and 0, 4, 6 scores, respectively in normal ovarian tissue, primary lesion of ovarian cancer, and omentum metastatic tissue. Transwell assay showed that the number of invasive HEY cells in ACC1 overexpression group was more than that in NC group [(87.7±7.4) vs. (52.2±4.2), t = 5.19, P = 0.003]. The number of invasive HEY cells in ACC1-sh1 group, and ACC1-sh2 group with the knockdown of ACC1 was less than that in shNC group [(21.2±1.5), (29.7±2.3) vs. (56.2±5.3); t value was 6.41, 3.77; P < 0.001, P < 0.005]. The number of lipid droplets in HEY cells in the ACC1 overexpression group was more than that in the control NC group [Oil red O staining: (301±25) vs. (215±21); Nile red staining: (287±15) vs. (207±10); all P < 0.05]; the number of lipid droplets in HEY cells in ACC1-sh1 and ACC1-sh2 group with the knockdown of ACC1 was less than that in ACC1-shNC group [Oil red O staining: (113±8), (119±12) vs. (195±18); Nile red staining: (82±8), (117±11) vs. (165±17); all P < 0.05]. The result of dual luciferase reporter assay showed that overexpression of YY1 promoted the luciferase activity of the wild type ACC1 promoter region report gene ( P = 0.003), while the luciferase activity of the report gene was inhibited compared with the wild type after the mutation of binding sites of YY1 in ACCI promoter region ( P = 0.008). Western blot results showed that the expression levels of YY1 and ACC1 protein in HEY cells with YY1 overexpression group were higher than those in NC group, which indicated a synergistic increasing trend of both YY1 and ACC1; the expression levels of YY1 and ACC1 protein in YY1-sh1 group, YY1-sh2 group and YY1-sh3 group with the knockdown of YY1 were lower than those in the control YY1-shNC group, which indicated a synergistic decreasing trend of both YY1 and ACC1. Conclusions:ACC1 and YY1 are highly expressed in ovarian cancer metastatic tissues and both show a positive correlation trend. The expression level of ACC1 in vitro has an impact on cell migration and lipogenesis in ovarian cancer via YY1 transcriptionally regulating ACC1.

Application value of psTg combined with lymph node ratio in prognosis of papillary thyroid cancer patients treated with 131I / 中华核医学与分子影像杂志

Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.

Analysis of misdiagnosed cases of neck, shoulder, waist and leg pain caused by bone metastases and early warning measures / 中国基层医药

Objective:To investigate the cause of misdiagnosis of neck, shoulder, waist, and leg pain caused by bone metastases and to improve the outpatient diagnosis rate.Methods:Five misdiagnosed cases of bone metastases who were admitted to the Traditional Chinese Medicine Department of Orthopedics and Traumatology, School of Traditional Chinese Medicine, Southern Medical University from January 2019 to July 2020 were included in this study. Their clinical manifestations, diagnosis results (outside hospital diagnosis and outpatient diagnosis), and imaging manifestations were retrospectively analyzed.Results:Five cases of bone metastases were misdiagnosed to have cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain. Accelerated red blood cell sedimentation rate and increased C-reactive protein level were found in all five cases. Bone metastases were confirmed by X-ray, CT, and MRI examination results. All of them had warning signs for bone metastasis: age > 50 years, history of a tumor, unexplained weight loss, general malaise, neck, shoulder, waist, and leg pain without an obvious cause, sudden worsening of pain, night pain, resting pain, pain on direct palpation, no obvious improvements in these symptoms after symptomatic treatment for 1 month, disease development not conforming to the general law of cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain, increases in red blood cell sedimentation rate, C-reactive protein, and alkaline phosphatase levels, which are not consistent with the symptoms of cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain, and slight external force leading to fractures.Conclusion:Further tests and imaging examinations should be performed according to warning signs. Clinical schemes of malignant bone tumors suitable for general practitioners can easily, economically, and effectively identify malignant bone tumors.

Presumptive Prostate Cancer Presenting as Low Back Pain in the Chiropractic Office: Two Cases and Literature Review.

Prostate cancer is a common type of cancer in men and may metastasize to the spine and pelvis, causing back and/or radicular pain that appears to be musculoskeletal. This presents a diagnostic challenge and can be complicated by a lack of routine screening for prostate cancer. In two similar cases, elderly males (ages 78 and 82) with no known history of cancer and no previous prostate-specific antigen screening presented to a chiropractor with chronic, worsening radiating low back pain. In each case, a previous provider obtained radiographs and ascribed symptoms to a non-cancerous etiology (i.e., lumbar spondylosis, osteoporotic compression fracture), treated with nonsteroidal anti-inflammatory medications and physiotherapy. Given each patient's progressive worsening and neurologic deficits, the chiropractor ordered lumbar magnetic resonance imaging, revealing potential spinal metastasis. The chiropractor referred each patient to an oncologist who performed additional testing, making a presumptive diagnosis of prostate cancer. A literature review identified seven cases of previously undiagnosed prostate cancer presenting to a chiropractor. Including the current cases, patients were often older, presenting with thoracolumbar pain caused by spine or pelvic metastasis. The current cases and literature review illustrate that men with undiagnosed metastasis from prostate cancer may present to chiropractors complaining of spinal pain. Chiropractors should be aware of red flags warranting imaging such as older age and new or progressive symptoms and should refer patients to an oncologist when suspecting prostate cancer.

Chemotherapy Utilization in Men with Advanced Penile Cancer.

Introduction: Although studies using mixed insurance populations suggest that chemotherapy use in men with advanced penile cancer (PC) is low, it is unclear what regimens are being utilized. In this study, we use a database of insured patients to better understand specific chemotherapy utilization in men with PC. Methods: This is a retrospective cohort study of patients with stage IIIB or IV PC in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2015). Standard of care (SOC) chemotherapy was defined by the National Comprehensive Cancer Network® guidelines: 4 cycles of paclitaxel, ifosfamide and cisplatin or 5-fluorouracil with cisplatin in the neoadjuvant, adjuvant or primary setting. We calculated what proportion of patients receive SOC or any chemotherapy within 2 years of diagnosis and analyzed what factors were associated with receiving chemotherapy. Results: Our study included 147 patients-48 stage IIIB and 99 stage IV. Of these patients, 49 (33%) received chemotherapy. Less than 5% of men received SOC. About 10% received SOC chemotherapy but an insufficient number of cycles. Married men were more likely to undergo chemotherapy (OR 3.4, 95% CI 1.5-7.8). Less than 5% of the 24 Black or Hispanic patients received chemotherapy compared to 37% of white patients (p <0.001). Conclusions: Only a third of men with stage IIIB/IV PC underwent chemotherapy. Less than 5% of men received complete guideline-based regimens. Whether this is driven primarily by patient or provider factors is unknown, although social determinants of health may play a role. These data highlight the difficulty for patients with PC to get chemotherapy.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy.

PURPOSE: The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy. MATERIALS AND METHODS: In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index. RESULTS: In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men. CONCLUSIONS: In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

Outcomes of Stable Lung Colorectal Metastases on Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have demonstrated benefit in patients with colorectal peritoneal metastases (CRPM). Traditionally, extraperitoneal disease is considered a contraindication to CRS/HIPEC. Stable lung metastases in patients with colorectal cancer often have an indolent course, while the presence of untreated peritoneal metastases poorly affects short-term survival. We sought to evaluate the outcomes of patients undergoing CRS/HIPEC for peritoneal disease with known stable lung metastases. METHODS: We retrospectively reviewed our prospectively maintained CRS/HIPEC database. In 2017, we adopted a policy of considering patients with stable lung metastases for CRS/HIPEC as part of multidisciplinary treatment. We compared the oncologic outcome and safety of CRS/HIPEC with peritoneal only (PM) against patients with peritoneal and lung metastases (PLM). RESULTS: Our database includes 570 patients with CRS/HIPEC of which 174 with CRPM that underwent CRS/HIPEC, 18 with preoperatively diagnosed peritoneal and lung metastases. The demographics of the PM and PLM group were similar with the exception of operative time that was longer in the PLM group. Median PCI of the cohort was 7, similar in both groups (p = 0.89). Three-year overall survival (OS) of PLM patients was 68%, compared to 71% in PM (p = 0.277). Three-year progression-free survival (PFS) rate was 20% in PLM and 23% in PM (p = 0.688). CONCLUSIONS: Presence of stable lung metastases from colorectal cancer in patients with CRPM does not appear to affect the outcomes of CRS/HIPEC. Patients with stable lung disease should be considered for CRS/HIPEC after multidisciplinary discussion.

Metástasis duodenal por hipernefroma, reporte de un caso / Duodenal metastasis from hypernephroma: a case report

RESUMEN Introducción: el hipernefroma representa del 2 % al 3 % de todas las neoplasias malignas del adulto. Sus patrones de metástasis no han sido definidos con precisión. La metástasis duodenal es considerada rara cuando se presenta. Presentación del caso: paciente masculino, de 48 años de edad, con antecedentes de nefrectomía derecha por presentar hipernefroma que a los siete meses de la intervención se diseminó a pulmón y fosa renal. Al año de la nefrectomía es valorado por presentar anemia crónica, sangre oculta en heces fecales positiva y sintomatología gastrointestinal. Se realizó colon por enema opaco que reveló infiltración de la pared y durante la realización de gastroscopia se realizó toma de muestra de lesión tumoral en duodeno. El análisis anatomopatológico de la biopsia duodenal mostró una lesión tumoral de células grandes anaplásicas con citoplasma vacuolado, PAS positivas y PAS Diastasa negativas, compatible con metástasis de carcinoma de células renales. Conclusiones: la aparición tardía de metástasis y la regresión espontánea del hipernefroma exigen un seguimiento integral y prolongado del personal médico a su cargo, en quienes la sospecha de diseminación siempre debe preponderar durante el abordaje clínico, aun cuando la clínica no sugiera los sitios más comunes.

ABSTRACT Introduction: hypernephroma represents 2 % to 3 % of all adult malignant neoplasms. Its metastatic patterns have not been precisely defined. Duodenal metastasis is considered rare when it occurs. Case Report: a 48-year-old-male patient, having a history of right nephrectomy due to hypernephroma, at 7 months after the surgery a spread to the lung and renal fossa was found. One year after nephrectomy he was evaluated for chronic anemia, positive fecal occult blood and gastrointestinal symptoms. An opaque colon enema was performed which revealed infiltration of the wall and during gastroscopy a sample of tumor lesion in the duodenum was taken. The pathological analysis of the duodenal biopsy showed an anaplastic large cell tumor lesion with vacuolated cytoplasm, PAS positive and PAS Diastase negative, compatible with metastasis of renal cell carcinoma. Conclusions: the late appearance of metastases and spontaneous regression of hypernephroma require a comprehensive and prolonged follow-up by the medical staff in charge, in those where the suspicion of dissemination should always prevail during the clinical approach, even when the clinical picture does not suggest the most common sites.

Active Surveillance for Risk Stratification of All Small Renal Masses Lacking Predefined Clinical Criteria for Intervention.

PURPOSE: Despite general indolence of small renal masses and no known adversity from treatment delays, broad usage of active surveillance as a means to risk-stratify patients with small renal masses for more selective treatment has not been studied. We describe outcomes for a novel approach in which active surveillance was recommended to all patients with small renal masses lacking predefined progression criteria for intervention. MATERIALS AND METHODS: All nondialysis dependent patients with nonmetastatic small renal masses seen by 1 urologist at a comprehensive cancer center during January 2013-September 2017 were managed with active surveillance if standardized progression criteria for intervention were absent, with delayed intervention recommended only upon progression criteria for intervention development. Progression criteria for intervention were defined prospectively as small renal mass-related symptoms, unfavorable histology, cT3a stage or either of the following without benign neoplastic biopsy histology: longest tumor diameter >4 cm; growth rate >5 mm/year for longest tumor diameter ≤3 cm or >3 mm/year for longest tumor diameter >3 cm. RESULTS: In all, 96% (123/128) of patients with small renal masses lacked progression criteria for intervention at presentation and underwent active surveillance. With median/mean 31/34 months followup, none developed metastasis and 30% (37/123) developed progression criteria for intervention, 78% (29/37) of whom underwent delayed intervention. One (1%) patient crossed over to delayed intervention without progression criteria for intervention. Three-year progression criteria for intervention-free and delayed intervention-free rates were 72% and 75%, respectively. Delayed intervention resections were enriched (62%) for pT3 and/or nuclear grade 3-4 malignant pathology, with no benign resections. CONCLUSIONS: Active surveillance using predefined progression criteria for intervention in otherwise unselected patients with small renal masses allows intervention to be focused on at-risk small renal masses with common adverse pathology, avoiding treatment for most patients with small renal masses. Long-term delayed intervention and oncologic safety require study.

Advances of traditional Chinese medicine in prevention and treatment of recurrence and metastasis of liver cancer / 临床肝胆病杂志

Great achievements have been made in traditional Chinese medicine in the prevention and treatment of liver cancer in recent years. Studies have shown that traditional Chinese medicine can reduce the recurrence and metastasis of liver cancer and prolong the survival time of patients by inhibiting cell proliferation, inducing cell apoptosis, inhibiting cell migration and invasion, inhibiting angiogenesis, regulating immunity, and reversing drug resistance. This article reviews the clinical and basic studies on the effect of traditional Chinese medicine in the prevention and treatment of recurrence and metastasis of liver cancer in the recent 10 years, and it is believed that traditional Chinese medicine has the advantages of low toxicity, multiple targets, and multiple pathways in the prevention and treatment of recurrence and metastasis of liver cancer. Future research should focus on how to screen out the effective constituents for liver cancer, how to understand the complete mechanism of action of traditional Chinese medicine, whether the consistency in the efficacy of traditional Chinese medicine between in vivo and in vitro studies can be guaranteed, and whether there is a difference in the role of investigational drugs between populations from different regions in multicenter clinical studies.

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. OBJECTIVES: Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. DESIGN: A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. SETTING: Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. PARTICIPANTS: Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTIONS: Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. MAIN OUTCOME MEASURES: Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. RESULTS: In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. CONCLUSIONS: Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52040363. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information.

In about 50% of people with bowel cancer, cancer spreads to the liver (colorectal liver metastases) within 5 years of detection and treatment. Liver resection (i.e. surgical removal of a portion of the liver) is the standard treatment in people below 70 years of age who are otherwise well, provided that the liver cancer is confined to a limited part of the liver. Such patients are considered 'low-risk' patients. Older patients and those with major medical problems or extensive cancers are considered 'high-risk' patients, as they are at a higher risk of developing complications following liver resection. Thermal ablation destroys the liver cancers using a needle that heats the cancer deposits until they are destroyed. There is significant uncertainty as to whether or not ablation can offer equivalent survival compared with surgery for 'high-risk' patients. We planned and conducted a randomised controlled trial comparing ablation with surgery to resolve this uncertainty. In this trial, some patients received ablation and others received surgery. The treatment was allocated at random with neither patients nor the study organisers choosing the treatment. The trial had an internal pilot (i.e. a smaller version of the full trial to resolve any 'teething problems' and ensure that a sufficient number of participants can be included in the full trial). Only nine patients were recruited in the 1-year internal pilot, compared with the anticipated recruitment of 45 patients. Therefore, the trial closed early as a result of poor recruitment, and the uncertainty about the best treatment for high-risk patients with colorectal liver metastases continues. The main reasons for the poor recruitment included fewer than anticipated eligible participants, clinicians' unconscious bias towards surgery, and patients' preference for one treatment or the other. In the future, comparisons involving two very different treatments may benefit from a feasibility study or a longer period of pilot study to resolve any difficulties.

Strength of the Association of Elevated Vitamin B12 and Solid Cancers: An Adjusted Case-Control Study.

The association between elevated plasma vitamin B12 (B12) level and solid cancers has been documented by two national registries. However, their design did not allow for the adjustment for other conditions associated with elevated B12. The objectives of this study were to confirm this association after the adjustment for all causes of elevated B12, and to study the variations according to the increasing B12 level, the type of cancers, and the presence of metastases. We compared 785 patients with B12 ≥ 1000 ng/L with 785 controls matched for sex and age with B12 < 1000 ng/L. Analyses were adjusted for the causes of elevated B12: myeloid blood malignancies, acute or chronic liver diseases, chronic kidney failure, autoimmune or inflammatory diseases, and excessive B12 supplementation. A B12 ≥ 1000 ng/L was associated with the presence of solid cancer without metastases (OR 1.96 [95%CI: 1.18 to 3.25]) and with metastases (OR 4.21 [95%CI: 2.67 to 6.64]) after adjustment for all elevated B12-related causes. The strength of the association rose with the increasing B12 level, in particular in cases of metastases. No association between liver cancers and elevated B12 level was found after adjustment for chronic liver diseases. In conclusion, unexplained elevated B12 levels should be examined as a possible marker of solid cancer.

Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening?

BACKGROUND: Current National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines recommend against screening breast cancer patients for asymptomatic brain metastases. Because brain metastases are a major cause of morbidity and mortality from breast cancer, we undertook a literature review to ascertain whether there might be a role for brain metastases screening in high-risk patient subgroups. MATERIALS AND METHODS: A literature search was conducted on the OvidSP platform in the MedLine database, using MeSH terms and subject headings related to breast cancer, brain metastases, and incidence. The search was conducted without language or publication restrictions, and included articles indexed from January 1, 2006 to June 10, 2018. Experimental and observational studies that reported the incidence of brain metastases in patients with nonmetastatic or metastatic breast cancer were included. RESULTS: One hundred seventy studies were identified, with 33 included in the final analysis. Among nonmetastatic breast cancer patients, incidence of brain metastases as site of first recurrence per year of median follow-up ranged from 0.1% to 3.2%. Although incidence of brain metastases was much higher among the metastatic breast cancer population overall, it was particularly high among metastatic HER2-overexpressing (HER2+) and triple-negative populations, ranging between 22% and 36% for the former, and 15%-37% for the latter in the absence of screening. CONCLUSION: In patients with nonmetastatic breast cancer, screening for asymptomatic brain metastases cannot currently be justified. However, due to the high incidence of brain metastases among patients with metastatic HER2+ and triple-negative breast cancer, studies to determine the value of screening for brain metastases should be undertaken in these subgroups.

Factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors of head and neck / 中华核医学与分子影像杂志

Objective@#To analyze the factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors in head and neck.@*Methods@#A total of 73 patients (61 males, 12 females; age: (59.1±11.5) years) with head and neck tumors recurrence and metastasis treated by 125I seeds implantation in Hebei General Hospital from January 2015 to April 2019 were retrospectively enrolled. The implanted seeds activity was 11.1-29.6 MBq, and the prescription dose was 80.0-145.0 Gy. CT examination was conducted 3 months after 125I seeds implantation. According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, short-term efficacy was classified as effective (complete remission (CR), partial remission (PR)) and ineffective (stable disease (SD), progressive disease (PD)). Univariate analysis of factors affecting short-term effect (gender, age, history of radiation therapy, Karnofsky performance status (KPS) scores, pathological type, the longest diameter of tumor, implantation patterns, seeds activity, immediate postoperative dose delivered to 90% gross tumor volume (D90), and with adjuvant chemotherapy post-surgery or not) were conducted. Variables with P<0.2 were enrolled in logistic multivariate regression analysis. In addition, artificial neural network (ANN) was constructed with all influencing factors as independent variables and short-term efficacy as dependent variables. Finally, receiver operating characteristic (ROC) curve analysis was performed for the common influencing factors in logistic regression analysis and ANN analysis.@*Results@#There were 34 with effective results and 39 with ineffective results. Logistic regression analysis indicated that the longest diameter of tumor, immediate postoperative D90, with adjuvant chemotherapy post-surgery or not had significant impacts on the short-term efficacy (Wald values: 6.950, 4.804, 4.790, all P<0.05); According to results of ANN analysis, the top 5 in order of importance for short-term efficacy prediction were immediate postoperative D90, the longest diameter of tumor, age, seeds activity and gender. ROC curve analysis indicated that the longest diameter of tumor and immediate postoperative D90 were the best predictors for short-term efficacy, with the threshold of 5.25 cm and 110.05 Gy respectively, and the area under the curve (AUC) was 0.843 and 0.847 respectively (both P<0.001).@*Conclusions@#The short-term efficacy of 125I seeds implantation in the recurrence and metastasis of head and neck tumors is mainly related to the longest diameter of tumor and immediate postoperative D90. Patients with the longest diameter of tumor <5.25 cm and with D90>110.05 Gy can achieve better efficacy.

Factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors of head and neck / 中华核医学与分子影像杂志

Objective To analyze the factors influencing the short-term efficacy of CT-guided 125I seeds implantation in the treatment of recurrent and metastatic tumors in head and neck.Methods A total of 73 patients (61 males,12 females;age:(59.1±11.5) years) with head and neck tumors recurrence and metastasis treated by 125I seeds implantation in Hebei General Hospital from January 2015 to April 2019 were retrospectively enrolled.The implanted seeds activity was 11.1-29.6 MBq,and the prescription dose was 80.0-145.0 Gy.CT examination was conducted 3 months after 125I seeds implantation.According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,short-term efficacy was classified as effective (complete remission (CR),partial remission (PR)) and ineffective (stable disease (SD),progressive disease (PD)).Univariate analysis of factors affecting short-term effect (gender,age,history of radiation therapy,Karnofsky performance status (KPS) scores,pathological type,the longest diameter of tumor,implantation patterns,seeds activity,immediate postoperative dose delivered to 90％ gross tumor volume (D90),and with adjuvant chemotherapy post-surgery or not) were conducted.Variables with P＜ 0.2 were enrolled in logistic multivariate regression analysis.In addition,artificial neural network (ANN) was constructed with all influencing factors as independent variables and short-term efficacy as dependent variables.Finally,receiver operating characteristic (ROC) curve analysis was performed for the common influencing factors in logistic regression analysis and ANN analysis.Results There were 34 with effective results and 39 with ineffective results.Logistic regression analysis indicated that the longest diameter of tumor,immediate postoperative D90,with adjuvant chemotherapy post-surgery or not had significant impacts on the shortterm efficacy (Wald values:6.950,4.804,4.790,all P＜0.05);According to results of ANN analysis,the top 5 in order of importance for short-term efficacy prediction were immediate postoperative D90,the longest diameter of tumor,age,seeds activity and gender.ROC curve analysis indicated that the longest diameter of tumor and immediate postoperative D90 were the best predictors for short-term efficacy,with the threshold of 5.25 cm and 110.05 Gy respectively,and the area under the curve (AUC) was 0.843 and 0.847 respectively (both P＜0.001).Conclusions The short-term efficacy of 125I seeds implantation in the recurrence and metastasis of head and neck tumors is mainly related to the longest diameter of tumor and immediate postoperative D90.Patients with the longest diameter of tumor ＜5.25 cm and with D90＞110.05 Gy can achieve better efficacy.

ASSESSING PSYCHOSOCIAL DISTRESS IN BONE METASTASES TREATED WITH ENDOPROSTHESIS.

OBJECTIVE: To compare preoperative and early postoperative levels of psychosocial distress in patients undergoing bone metastasis treatment with endoprosthesis, evaluating its impact on quality of life. METHODS: Thirteen patients undergoing endoprosthetic treatment of bone metastasis were assessed at two time points: preoperatively and 30 days postoperatively. The tool used was the Distress Thermometer, a questionnaire for psychosocial screening developed by the National Comprehensive Cancer Network. Distress is considered moderate or severe if the patient scores 4 or higher. RESULTS: The most frequent problems in the preoperative period were "bathing and dressing". At 30 days, "fatigue" and "nervousness" prevailed. There was a significant improvement in distress when preoperative and 30-day assessments were compared. CONCLUSION: The surgical treatment of bone metastasis with endoprosthesis results in an early improvement of psychosocial distress as measured by the Distress Thermometer. Level of evidence II, Prospective and comparative therapeutic study.

OBJETIVO: Confrontar o nível de angústia psicossocial (distress) entre o pré-operatório e o pós-operatório precoce de pacientes submetidos ao tratamento de metástase óssea com endoprótese, avaliando seu impacto na qualidade de vida. MÉTODOS: Foram avaliados 13 pacientes submetidos ao tratamento de metástase óssea com endoprótese em dois momentos: pré-operatório e pós-operatório de 30 dias. A ferramenta utilizada foi o termômetro de Distress, questionário de triagem psicossocial desenvolvido pela National Comprehensive Cancer Network. É considerado distress moderado ou grave se o paciente somar 4 ou mais pontos. RESULTADOS: No pré-operatório, os problemas mais frequentes foram "tomar banho e vestir-se". Com 30 dias, os itens mais prevalentes foram "cansaço" e "nervosismo". Houve melhora significativa do distress quando foram comparadas as avaliações pré-operatória e após 30 dias. CONCLUSÃO: O tratamento cirúrgico com endoprótese para metástase óssea reduz precocemente o nível de angústia psicossocial aferido pelo termômetro de Distress. Nível de evidência II, Estudo terapêutico, prospectivo e comparativo.