Our Experience of OSAKA Regimen (Bladder Preservation) in Patients with Advanced Bladder Cancer.

Introduction and Objectives: OSAKA regimen is a novel bladder preservation therapy involving balloon-occluded selective arterial infusion of radio-sensitizing chemotherapeutic agent with concurrent hemodialysis (HD), followed by radiation therapy. Objectives are to study the feasibility of this novel regimen in patients with advanced cancer bladder (Ca Bladder). Methods: Two patients having advanced Ca Bladder with cisplatin ineligibility and poor performance status were managed with OSAKA regimen. Patients undergo super selective catheterisation of the anterior division of the internal iliac artery, followed by concurrent instillation of cisplatin (100 mg) via microcatheters and hemodialysis. Within 72 h, definitive radiation therapy is given. Image-guided radiation therapy (IGRT) with Helical Tomo using an Accuracy Radixact Tomography machine was used. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin, with a boost of 10 Gray to bladder plus margin). Response is monitored by 3 monthly fluorodeoxyglucose positron emission tomography (FDG PET) imaging. Results: Our first patient tolerated the procedure well and showed a complete response at 3 months of FDG PET imaging, but unfortunately, 1 year of FDG PET showed bony metastases, and the patient was managed accordingly. Our second patient also tolerated the regimen well, showed a complete response at 3 and 12 months of FDG PET imaging, and is under follow-up. Conclusions: The OSAKA regimen, as a bladder preservation strategy, is feasible and safe in selective advanced Ca Bladder patients.

Primary Well-Differentiated Neuroendocrine Tumor of the Kidney.

Primary neuroendocrine tumors (NET) of the kidney are rare. They present with varied symptoms, making their diagnosis difficult clinically as well as pathologically. We present to you the case of a renal NET, which presented in a young female patient. A 48-year-old female patient came with an incidentally detected right renal mass during the evaluation of a nonspecific gynecological problem. She underwent contrast-enhanced computed tomography (CT) of the abdomen, which showed a 57*45*34 mm mass with enlarged retrocaval and aortocaval nodes (25*12 mm). Renal cell carcinoma was suspected as per the CT findings, and metastatic workup in the form of FDG PET CT was done in view of the unusually enlarged nodes. She underwent robot-assisted radical nephrectomy along with lymph node dissection. Surgery was uneventful, and she recovered well in the postoperative period. In the final pathology, there was confusion regarding the diagnosis, and further immunohistochemistry (IHC) was recommended by the pathologist. IHC showed synaptophysin positive, chromogranin negative, CD56 focally positive with Ki-67 of 2-3%, which was suggestive of low-grade NET of the kidney. Lymph nodes were negative. She was kept on follow-up and a Ga 68-DOTANOC scan at 3 months showed no evidence of disease. Diagnosis and management of NET of the kidney still remains a debatable and controversial topic in view of its rarity. High index of suspicion needs to be observed in patients presenting with carcinoid syndrome and a renal mass. Nuclear scans like PET scan and DOTANOC scan can accurately stage the disease. Management includes partial or radical nephrectomy depending on the tumor characteristics. Further studies are required to optimize the treatment protocols for these patients.

Peripheral cord insertion is associated with adverse pregnancy outcome only when accompanied by clinically significant placental pathology.

OBJECTIVE: To examine the relationship between umbilical cord insertion site, placental pathology and adverse pregnancy outcome in a cohort of normal and complicated pregnancies. METHODS: Sonographic measurement of the cord insertion and detailed placental pathology were performed in 309 participants. Associations between cord insertion site, placental pathology and adverse pregnancy outcome (pre-eclampsia, preterm birth, small-for-gestational age) were examined. RESULTS: A total of 93 (30%) participants were identified by pathological examination to have a peripheral cord insertion site. Only 41 of the 93 (44%) peripheral cords were detected by prenatal ultrasound. Peripherally inserted cords were associated significantly (P < 0.0001) with diagnostic placental pathology (most commonly with maternal vascular malperfusion (MVM)); of which 85% had an adverse pregnancy outcome. In cases of isolated peripheral cords, without placental pathology, the incidence of adverse outcome was not statistically different when compared to those with central cord insertion and no placental pathology (31% vs 18%; P = 0.3). A peripheral cord with an abnormal umbilical artery (UA) pulsatility index (PI) corresponded to an adverse outcome in 96% of cases compared to 29% when the UA-PI was normal. CONCLUSIONS: This study demonstrates that peripheral cord insertion is often part of the spectrum of findings of MVM disease and is associated with adverse pregnancy outcome. However, adverse outcome was uncommon when there was an isolated peripheral cord insertion and no placental pathology. Therefore, additional sonographic and biochemical features of MVM should be sought when a peripheral cord is observed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Doppler Ultrasound of the Fetal Descending Aorta: An Objective Tool to Assess Placental Blood Flow Resistance in Pregnancies With Discordant Umbilical Arteries.

OBJECTIVES: To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs). METHODS: Pulsed wave Doppler of both UAs and the descending aorta was performed at 4-weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI. RESULTS: Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008). CONCLUSIONS: The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto-placental circulation where discordant UA PIs are found.

Prognostic significance of metabolic tumour volume and maximum standard uptake value of fluor-18-fluorodeoxyglucose positron emission tomography with computed tomography in nasopharyngeal carcinoma.

AIM OF THE STUDY: To evaluate the prognostic role of markers of fluor-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET-CT), such as maximum standard uptake value (SUVmax) and metabolic tumour volume (MTV) measured at primary and nodal disease, and their clinical significance in terms of predicting treatment outcomes and survival. MATERIAL AND METHODS: Between January 2017 and January 2020, 20 case records of nasopharyngeal carcinoma patients who underwent 18F-FDG-PET-CT as part of staging workup before radiotherapy and as a part of response evaluation after radiotherapy were retrospectively reviewed. RESULTS: At a median follow-up of 34.7 months, the 2-year progression-free survival (PFS) was 70% and 2-year overall survival (OS) was 79%. Patients with a lower nodal SUVmax (SUVmax-N) had a better 2-year PFS (91% vs. 46%; p = 0.035) and 2-year OS (95% vs. 58%; p = 0.015). A high SUVmax-N of > 10.58 was a negative predictor of OS (95% confidence interval [CI]: 0.93-1; p = 0.003) as well as PFS (95% CI: 0.64-1; p = 0.017). Also, a high MTV > 25.8 cm3 was a negative predictor of PFS (95% CI: 0.58-0.98; p = 0.048). MTV was an independent predictor of PFS and OS on univariate analysis, whereas it was not significant in the Cox regression multivariate analysis. CONCLUSIONS: High values of MTV and SUVmax-N can be considered as independent prognostic factors of OS and PFS in nasopharyngeal cancer patients treated with concurrent chemoradiation, highlighting the need for more intensified treatment.

Wave reflections in the umbilical artery measured by Doppler ultrasound as a novel predictor of placental pathology.

BACKGROUND: The umbilical artery (UA) Doppler pulsatility index is used clinically to detect elevated feto-placental vascular resistance. However, this metric is confounded by variation in fetal cardiac function and is only moderately predictive of placental pathology. Our group developed a novel ultrasound methodology that measures wave reflections in the UA, thereby isolating a component of the Doppler signal that is specific to the placenta. The present study examined whether wave reflections in the UA are predictive of placental vascular pathology. METHODS: Standard clinical Doppler ultrasound of the UAs was performed in 241 pregnant women. Of these, 40 women met narrowly defined preset criteria for the control group, 36 had maternal vascular malperfusion (MVM) and 16 had fetal vascular malperfusion (FVM). Using a computational procedure, the Doppler waveforms were decomposed into a pair of forward and backward propagating waves. FINDINGS: Compared to controls, wave reflections were significantly elevated in women with either MVM (p<0.0001) or FVM pathology (p = 0.02). In contrast, the umbilical and uterine artery pulsatility indices were only elevated in the MVM group (p<0.0001) and there were no differences between women with FVM and the controls. INTERPRETATION: The measurement of wave reflections in the UA, combined with standard clinical ultrasound parameters, has the potential to improve the diagnostic performance of UA Doppler to detect placental vascular pathology. Identifying women with FVM pathology is particularly challenging prenatally and future investigations will determine if women at risk of this specific placental disease could benefit from this novel diagnostic technique.

Development of an Indian nomogram for predicting extracapsular extension in prostate cancer.

INTRODUCTION: The aim of our study was to develop a new Indian nomogram to estimate pathologic extracapsular extension (ECE) risk in prostate cancer, by including PI-RADS v1-based magnetic resonance imaging (MRI) ECE risk score to the clinical variables used in the Partin nomogram (PN). MATERIALS AND METHODS: We analyzed 273 patients who underwent MRI of prostate and radical prostatectomy (RP). Univariate and multivariate logistic regression analyses were performed to identify predictors of ECE. We calculated the area under the receiver operating characteristic curve (AUC) for three variables used in PN and MRI ECE risk score, and a new nomogram was designed using binary logistic regression. Calibration curves assessed the agreement between the actual ECE risk and the predicted probability of the new nomogram. RESULTS: Out of 273 patients, 123 patients (45.1) had ECE on MRI, whereas 136 patients (49.8) had ECE on final pathology. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI for predicting ECE were 76.6, 66.9, 70.0, 73.9, and 71.7 (confidence interval 95), respectively. Multivariate logistic regression analyses showed that clinical T-stage (cT), Gleason score (GS), and MRI ECE risk score remained significant. The highest and the lowest values of the AUC for single variables were 0.748 (MRI ECE risk score) and 0.636 (cT stage), respectively, and AUC for PN was 0.67. New nomogram designed using R statistical package has higher predictive accuracy (0.826) compared to PN (0.67) and good calibration. CONCLUSIONS: MRI adds incremental value to PN. A new Indian nomogram can help in the decision-making process of nerve-sparing RP. This nomogram should be used with caution as validation is pending and will require further studies.

Sex differences in fetal Doppler parameters during gestation.

BACKGROUND: Fetal sex is known to affect pregnancy outcomes. In current clinical practice, monitoring of fetal well-being is based on Doppler ultrasound measurements of major placental and fetal vessels. The objective of this study was to investigate the effect of fetal sex on Doppler parameters throughout gestation in healthy pregnancy. METHODS: A prospective study was conducted in 240 pregnant women with ultrasound examinations at a 4-weekly interval between 12 and 38 weeks of gestation. Pulsed Doppler spectra were collected for the umbilical arteries (UAs), middle cerebral artery (MCA), descending abdominal aorta (DAo), and ductus venosus (DV). Linear mixed effects models were used to determine if the pulsatility indices (PIs) of these vessels depended on gestational age and fetal sex. RESULTS: While there were no differences in the MCA PI and DV PIV over gestation between female and male fetuses, the trajectory of the UA and DAo PIs differed by fetal sex (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Doppler ultrasound parameters were found to be dependent on fetal sex for some vessels and not for others in healthy pregnancies. Further investigations are needed to understand the physiological mechanisms for these sex differences and the relevance for disease processes in pregnancy.

Sex differences in modulation of fetoplacental vascular resistance in growth-restricted mouse fetuses following betamethasone administration: comparisons with human fetuses.

BACKGROUND: Maternally administered corticosteroids are routinely used to accelerate fetal lung maturation in pregnancies at risk of early preterm delivery. Although, among the subgroup with growth restriction, a majority show a temporary improvement in umbilical artery Doppler waveforms that may be sustained up to 7 days, a minority will acutely decompensate in response to corticosteroids in association with deteriorating umbilical and fetal Doppler waveforms. The basis for such acute Doppler changes is presently unknown. Our group has developed a noninvasive ultrasound methodology to measure wave reflections in the umbilical artery and have established that wave reflection metrics are sensitive to structural changes in the placental vasculature and to acute changes in vascular tone. Using this approach, we demonstrated in healthy pregnant mice that fetoplacental vascular resistance decreased in betamethasone-treated mice compared with saline-treated controls. OBJECTIVE: This study aimed to investigate the effects of betamethasone administration on the wave reflection metrics in a mouse model of fetal growth restriction and to compare these findings with equivalent measurements in human fetuses. STUDY DESIGN: Pregnant CD-1 mice were housed from embryonic day 14.5 to embryonic day 17.5 in either a normoxic (21% O2, n=24) or hypoxic environment (11% O2, n=22), the latter being an established mouse model of fetal growth restriction. To investigate the effect of maternally administered betamethasone on the fetoplacental vasculature, ultrasound imaging was performed at baseline and 4 hours after treatment (either betamethasone or sterile saline). Umbilical artery wave reflection metrics were compared between the groups and for the effect of fetal sex. In addition, a cohort of 10 pregnant women with elevated umbilical artery pulsatility index and evidence of fetal growth restriction and 6 controls were imaged before and after corticosteroid administration. RESULTS: In the mouse model, after betamethasone administration, the female fetuses from the hypoxia group showed a 15% increase in umbilical artery diameter, a 98% increase in umbilical artery blood flow, and a 27% decrease in umbilical artery reflection coefficient, whereas the males from the hypoxia group showed no substantial changes. In agreement with our mouse findings, umbilical artery reflections were found to be larger in human growth-restricted fetuses than controls in women at risk of preterm birth. CONCLUSION: Our studies provide insight into the mechanism whereby the human growth-restricted fetus may exhibit a temporary favorable fetoplacental vascular response to maternally administered corticosteroids. Further investigations are needed to understand why the male growth-restricted fetus seems unable to mount this favorable vascular response.

Determination of fetal heart rate short-term variation from umbilical artery Doppler waveforms.

OBJECTIVE: To evaluate the feasibility of using umbilical artery (UA) Doppler waveforms to measure fetal heart rate (FHR) short-term variation (STV) across gestation. METHODS: This was a prospective longitudinal study, conducted at two study sites, of 195 pregnancies considered low risk. Pulsed-wave Doppler of the UAs was performed at 4-weekly intervals, between 14 and 40 weeks of gestation, using a standardized imaging protocol. Up to 12 consecutive UA Doppler waveforms were analyzed using offline processing software. FHR STV was calculated using average R-R intervals extracted from the waveforms and baseline corrected for FHR. RESULTS: Baseline-corrected FHR STV increased significantly with gestational age (conditional R2 = 0.37; P < 0.0001) and was correlated inversely with FHR (conditional R2 = 0.54; P < 0.0001). The STV ranged (median (interquartile range)) from 3.5 (2.9-4.1) ms at 14-20 weeks' gestation to 6.3 (4.8-7.7) ms at 34-40 weeks' gestation. The change in heart rate STV did not differ between study sites or individual sonographers. CONCLUSIONS: UA Doppler waveforms offer a robust and feasible method to derive STV of the FHR. It should be emphasized that the UA Doppler-derived STV is not interchangeable with measurements derived with computerized cardiotocography. Accordingly, further investigations are needed to validate associations with outcome, in order to determine the value of concurrent fetal cardiovascular and heart rate evaluations that are possible with the technique described here. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.