Planetary health: an imperative for pediatric radiology.

The global temperature has been increasing resulting in climate change. This negatively impacts planetary health that disproportionately affects the most vulnerable among us, especially children. Extreme weather events, such as hurricanes, tornadoes, wildfires, flooding, and heatwaves, are becoming more frequent and severe, posing a significant threat to our patients' health, safety, and security. Concurrently, shifts in environmental exposures, including air pollution, allergens, pathogenic vectors, and microplastics, further exacerbate the risks faced by children. In this paper, we provide an overview of pediatric illnesses that are becoming more prevalent and severe because of extreme weather events, global temperature increases, and shifts in environmental exposures. As members of pediatric health care teams, it is crucial for pediatric radiologists to be knowledgeable about the impacts of climate change on our patients, and continue to advocate for safe, healthier environments for our patients.

Changes to pediatric brain tumors in 2021 World Health Organization classification of tumors of the central nervous system.

New tumor types are continuously being described with advances in molecular testing and genomic analysis resulting in better prognostics, new targeted therapy options and improved patient outcomes. As a result of these advances, pathological classification of tumors is periodically updated with new editions of the World Health Organization (WHO) Classification of Tumors books. In 2021, WHO Classification of Tumors of the Central Nervous System, 5th edition (CNS5), was published with major changes in pediatric brain tumors officially recognized including pediatric gliomas being separated from adult gliomas, ependymomas being categorized based on anatomical compartment and many new tumor types, most of them seen in children. Additional general changes, such as tumor grading now being done within tumor types rather than across entities and changes in definition of glioblastoma, are also relevant to pediatric neuro-oncology practice. The purpose of this manuscript is to highlight the major changes in pediatric brain tumors in CNS5 most relevant to radiologists. Additionally, brief descriptions of newly recognized entities will be presented with a focus on imaging findings.

Gadolinium retention: should pediatric radiologists be concerned, and how to frame conversations with families.

Gadolinium retention in the brain and other organs has recently been identified by imaging and confirmed histologically. No direct clinical effects of gadolinium retention, which occurs after gadolinium-based contrast agent (GBCA) administration for MRI, have been scientifically accepted at this time. However, there is understandable concern among medical professionals and the public about the potential effects of gadolinium retention, particularly in the brain. Part of this concern might stem from the identification of nephrogenic systemic fibrosis caused by GBCAs in people with severe renal failure in 2006. This article briefly describes the characteristics of GBCAs; reviews and differentiates gadolinium retention, nephrogenic systemic fibrosis, and "gadolinium deposition disease" or "gadolinium toxicity"; and discusses societal guidelines and current usage in children. With the belief that GBCAs should not be withheld for appropriate indications in the absence of evidence of its potential risks, we offer a framework for determining when GBCA use is appropriate and suggestions for discussing its risks and benefits with children and their families.

Development of a nomogram incorporating serum C-reactive protein level to predict overall survival of patients with advanced urothelial carcinoma and its evaluation by decision curve analysis.

BACKGROUND: The purpose of this study is to investigate the prognostic impact of C-reactive protein (CRP) on patients with advanced urothelial carcinoma and to develop a novel nomogram predicting survival. METHODS: A total of 223 consecutive patients were treated at Tokyo Medical and Dental Hospital. A nomogram incorporating V was developed based on the result of a Cox proportional hazards model. Its efficacy and clinical usefulness was evaluated by concordance index (c-index) and decision curve analysis. RESULTS: Of the 223 patients, 184 (83%) died of cancer. Median follow-up periods of patients who died and those who remained alive were 5 and 11 months, respectively. We developed a novel nomogram incorporating Eastern Cooperative Oncology Group Performance Status, presence of visceral metastasis, haemoglobin and age. The c-index of the nomogram predicting survival probability 6 and 12 months after diagnosis was 0.788 and 0.765, respectively. Decision curve analyses revealed that the novel nomogram incorporating CRP had a superior net benefit than that without CRP for most of the examined probabilities. CONCLUSION: We demonstrated the prognostic impact of CRP that improved the predictive accuracy of a nomogram for survival probability in patients with advanced urothelial carcinoma.

Olfactory discrimination of structurally similar alcohols by cockroaches.

The capability of the cockroach Periplaneta americana to discriminate odors of structurally similar aliphatic alcohols was studied by using an operant conditioning paradigm. Cockroaches were trained to discriminate three odors: one odor associated with sucrose solution (reward) and two odors associated with NaCl solution (non-reward). After training, their odor preferences were tested by counting the number of visits to each odor source. We tested the capability of cockroaches to discriminate (1) three normal aliphatic alcohols with different numbers of carbon (1-pentanol, 1-hexanol and 1-octanol), (2) three C6 aliphatic alcohols (1-hexanol, 2-hexanol and trans-2-hexen-1-ol), (3) binary mixtures of two of these three alcohols and their components, and (4) 1-hexanol solution of three different concentrations (1, 10 and 100 micro g micro l(-1)). Cockroaches exhibited higher preferences for the odors associated with reward in these tests, and we therefore conclude that cockroaches can discriminate these odors. However, discrimination of 1-hexanol and trans-2-hexen-1-ol and their binary mixture was imperfect, in that some statistical tests suggested significant level of discrimination but other tests did not. In addition, the cockroaches learned to associate a 1-hexanol solution of the highest or lowest concentration with sucrose reward but failed to learn to associate 1-hexanol of an intermediate concentration with reward.

Applicability of a mobile accelerator for intraoperative radiation therapy to colorectal cancer.

PURPOSE: Intraoperative radiation therapy is reportedly effective for local control and pain relief in colorectal cancer. However, this treatment requires a large number of medical personnel, which hinders expanded use of this method. A mobile electron linear accelerator for intraoperative radiation therapy has been developed and is now commercially available. This report analyzes the applicability of this accelerator to colorectal cancer. The applicability of the mobile accelerator is analyzed based on its specifications by simulating the intraoperative radiation therapy delivered to these patients with a conventional intraoperative radiation therapy unit. METHODS: From 1987 to 1999, 49 colorectal cancer patients underwent 54 surgical resections and received intraoperative radiation therapy to 75 sites. RESULTS: The mean intraoperative radiation therapy dose for colorectal cancer with the conventional unit was 22 (range, 10-30) Gy. The mean electron energy level was 10 (range, 3-30) MEV. Applicator size ranged from 4 to 10 cm in diameter. The mobile accelerator can achieve a dose rate of 10 Gy/min and an applicator unit size range of 3 to 10 cm in diameter, facilitating intraoperative radiation therapy for colorectal cancer. The electron energy limitation (12 MEV at maximum) suggests that the indications for this machine are limited. In our experience, 30 percent of patients received intraoperative radiation therapy with electron energy levels exceeding 12 MEV. Of these cases, 81 percent had macroscopic residual tumor and 69 percent had pain. CONCLUSION: An intraoperative radiation therapy mobile accelerator can cover 72 percent of the irradiation sites covered using our conventional unit. This accelerator is useful for intraoperative radiation therapy with curative intent for patients with no or slight residual tumor. Patients with gross residual tumor and pain may not be suitable.

A novel monoclonal antibody that recognizes human perivascular cells of the central nervous system under a specific immune reaction.

Perivascular cells or fluorescent granular perithelial cells of the central nervous system are newly recognized members of monocyte/macrophage populations. In this study a monoclonal antibody, GP-3, that labels proteinous lysosomal antigen of human perivascular cells, has been established. It selectively label the cells in foamy-macrophage infiltrating diseased areas, such as Wallerian degeneration and contusion, without significant reaction to the cells in normal areas, infiltrating macrophages or microglia. These findings suggest that the perivascular cell is an independent cell type and the antigen molecule is fairly specific to perivascular cells and plays an unknown role in immune-nervous system interaction.

Intraoperative irradiation after surgery for locally recurrent rectal cancer.

PURPOSE: This study retrospectively evaluated the effects of intraoperative electron beam irradiation on patients with locally recurrent (pelvic) rectal cancer. METHODS: From November 1, 1975, to December 31, 1997, 51 patients underwent surgery for locally recurrent rectal or rectosigmoid cancer, and 27 patients received intraoperative electron beam irradiation. The intraoperative electron beam irradiation dose was 15 to 30 Gy. Kaplan-Meier survival estimates at three and five years were analyzed for the 47 patients who recovered postoperatively. RESULTS: Statistically significant factors related to survival included intraoperative electron beam irradiation vs. no intraoperative electron beam irradiation (P=0.0007), amount of residual tumor (slight vs. gross; P=0.0022), and symptom status (P=0.0024). Factors not associated with survival included distant metastases at reoperation, type of surgery for the recurrent tumor, external beam irradiation, pathologic grade, age, and gender. Surgical resection without intraoperative electron beam irradiation resulted in three-year and five-year survival rates of 5 and 0 percent, respectively. For patients who received intraoperative electron beam irradiation, the three-year survival rate was 43 percent and five-year survival rate was 21 percent. Intraoperative electron beam irradiation was a statistically significant factor related to survival in patients with and without distant metastasis (P=0.04 and P=0.0035, respectively), with slight residual tumor (P=0.0003), or with palliative surgery (P=0.0276). CONCLUSION: The trends seen in resection with intraoperative electron beam irradiation are encouraging with regard to improvements in survival as compared with studies not using intraoperative electron beam irradiation treatment.

Involvement of fibrinolytic factors in mid trimester amniotic fluid with development of severe early-onset preeclampsia.

Impaired placental development is a well-known pathogenesis in preeclampsia. The present study was undertaken to elucidate the involvement of fibrinolytic factors in amniotic fluid in midtrimester with development of severe early-onset preeclampsia. Amniotic fluid was obtained by amniocentesis at 15 to 18 weeks of gestation. All specimens were retrospectively identified according to the hospital records as coming from gestations that later had severe early-onset preeclampsia (severe preeclamptic group, n = 9) or gestations with normal outcomes (control group, n = 73). Fibrinolytic factors such as tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and t-PA-PAI-1 complex (PAI-C) of specimens were measured by enzyme-linked immunoassay. In the control group, concentrations of t-PA as well as PAI-1 in amniotic fluid remained at similar levels from 15 to 18 weeks, although PAI-1 levels were more than 10 times higher compared with t-PA levels. Levels of t-PA and PAI-1 in the severe preeclamptic group were not different from those of the control group. PAI-C levels gradually decreased from 15 through 18 weeks of gestation in the control group. PAI-C levels of the severe preeclamptic group were significantly lower than those of the control group (55.5 +/- 18.0% versus control; mean +/- standard deviation [SD], p <0.001). PAI-C, as the most specific indicator of the early stage of fibrinolytic activities, showed lower levels in midtrimester amniotic fluid in the severe preeclamptic group, suggesting fibrinolytic activities of amniotic fluid may have a significant role in the development of severe early-onset preeclampsia via impaired placental development in the latent stage of preeclampsia.

Elevated IL-6 in midtrimester amniotic fluid is involved with the onset of preeclampsia.

PROBLEM: The primary defect of placental development in preeclampsia is speculated to occur at midtrimester gestation. Abnormal feto-maternal immune reactions have been considered as factors in such defective placentation. METHOD OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and gestations measured for cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1 beta, IL-6, and IL-8). The effect of each cytokine on thrombomodulin levels was tested in cultured trophoblast cells. RESULTS: Among the measured cytokines, IL-6 and IL-8 were significantly elevated in the midtrimester amniotic fluid of the future preeclamptic group. Trophoblasts stimulated with TNF-alpha plus IL-6 had significantly decreased levels of cellular thrombomodulin compared to those without cytokine addition. CONCLUSIONS: Elevated cytokines in midtrimester amniotic fluid suggest an abnormal fetomaternal immune response occurring before the clinical manifestation of preeclampsia. Cytokine-induced suppression of thrombomodulin in trophoblasts may be directly involved in the pathogenesis of preeclampsia.

Elevated fetal fibronectin in midtrimester amniotic fluid is involved with the onset of preeclampsia.

OBJECTIVE: To examine early midtrimester amniotic fluid for its significance in pregnancy outcomes, especially with connection to the pathogenesis of preeclampsia. METHODS: A prospective, nested, case-control study was conducted. Fetal fibronectin in early midtrimester (16-20 weeks gestation) amniotic fluid was measured by EIA method. Results were compared by their pregnancy outcomes. RESULTS: Amniotic fluid levels of fetal fibronectin were significantly higher in the group subsequently developing severe preeclampsia (106.8 +/- 13.2 micrograms/ml, mean +/- SD, n = 12) compared with matched controls (66.7 +/- 7.1 micrograms/ml, n = 12) (p < 0.05). CONCLUSION: High levels of fetal fibronectin were found in the amniotic fluid of women subsequently developing severe preeclampsia before any symptom appear. Involvement of extracellular injury or cellular hyperactivity in the midtrimester placental site with the onset of preeclampsia is suggested.

Primary non-Hodgkin's lymphoma of the larynx.

Three cases of primary non-Hodgkin's lymphoma of the larynx are described. Histologically, two tumours belonged to the category of low grade B-cell lymphomas of the small cell type (extranodal marginal zone B-cell lymphoma and lymphoplasmacytoid lymphoma), and the third was classified as a peripheral T-cell lymphoma of unspecified type. The clinical stage was IE in two cases, and IV in another case. In two cases, complete remission was obtained with radical radiotherapy. But in the other case, which was histologically lymphoplasmacytoid lymphoma, the response to radiotherapy was poor, and surgery was required. There was no relapse subsequent to treatment. Primary non-Hodgkin's lymphoma of the larynx is rare. Several reported cases have clinical features similar to those of MALT-type lymphomas arising in other extranodal sites. Although most of the reported cases have been cured with radiotherapy, in some cases dissemination to other extranodal sites may occur. Therefore careful periodic evaluation is imperative.

[Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall].

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.

[Clinical evaluation of intra-operative radiotherapy combined with subtotal cystectomy for invasive bladder carcinoma].

From 1981 to 1994, intra-operative radiotherapy after subtotal cystectomy was performed on 22 patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. All the patients received 25 to 30 Gy of radiotherapy focused on trigonum and internal urethral orifice after subtotal cystectomy with uretero-cutaneostomy. Of 22 patients, 15 patients died. Five patients died of bladder cancer, one died of gastric cancer, one died of rectal cancer and the others died of pneumonia, heart failure, sepsis and senility. The five-year survival rate was 41% and the cause-specific five-year survival rate was 75%. Local recurrence was seen only in one patients, who received second intra-operative radiotherapy and recovered well in complete remission. We believe that intra-operative radiotherapy after subtotal cystectomy is useful for patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition.

The imbalance of plasminogen activators and inhibitor in preeclampsia.

OBJECTIVE: To evaluate the role of plasminogen activators (tPA uPA) and inhibitor (PAI-1) in the pathogenesis of preeclampsia. STUDY DESIGN: tPA uPA and PAI-1 antigens were measured in amniotic fluid, maternal plasma, and placental homogenates in normal pregnancy by ELISA method and compared with that of preeclampsia. RESULTS: In normal pregnancy, tPA, uPA and PAI-1 levels increase as the gestation advance, but the increment of PAI-1 in amniotic fluid (28.3-fold) is larger than that of tPA and uPA (1.8-fold, 8.5-fold) (p < 0.001). Decidua homogenates contained larger amount of PAI-1 than villi. Whereas, villi had higher levels of tPA uPA than decidua (p < 0.01). In preeclampsia, the significantly higher levels of PAI-1 were observed in AF and decidua tissue as compared to the normals (p < 0.01), and the increment of PAI-1 in preeclampsia is larger than that of tPA, uPA. CONCLUSIONS: The elevated PAI-1 level is associated with the preeclampsia and the imbalance between the plasminogen activators (tPA, uPA) and the inhibitor (PAI-1) might be involved in the pathogenesis of preeclampsia.

[Techniques for determining position from more than two radiographs intersecting at arbitrary angles in brachytherapy].

The least squares method and geometrical solution for calculating position were used in the two-projection method. Five coordinate systems were defined as a normal system, image system on film intersecting the beam central axes at an arbitrary angle and the projection, virtual coordinate and virtual image coordinate systems with beam central axis as one of the three coordinate axes to determine the geometrical relationship between a point and image on the film. Normal coordinates of the point were calculated by six geometrical solution sets and two forms of the least squares method using the rotation matrixes of the coordinate systems. One least squares method solves simultaneous nonlinear equations, and the other derives a strict solution from simultaneous linear equations. The latter least squares method has little physical meaning and is not as useful as the former. Although the former has physical meaning, the iterative approximation method should be used to determine position since a strict solution cannot be obtained directly. By these least squares methods, position is determined with less error using the projections at more than two focal spots.

[Determination of source position for four radiography systems with orthogonal projections in brachytherapy].

Four configurations of two X-ray tube positions are available for determining the position of a point using two orthogonal films. For each configuration, there are many formulas for calculating the coordinate of a point: the least squares methods with and without physical meaning, such as six sets of geometrical solutions, an approximation method with constant magnifications and so on. It is troublesome for a person in charge of treatment planning to directly derive a formula or select an appropriate formula from numerous ones for the four configurations. Thus, a method to easily apply the published formula for a configuration to the other three configurations is described in simulations and a clinical case using rotation matrixes of the right-handed coordinate system. Each diagonal element of the rotation matrixes is 1 or -1, and the other elements are 0.