[Estimation of Shooting Part Using a Camera with Depth Sensors and Pose Estimation Method and Automatic Setting of Optimal X-ray Imaging Conditions].

PURPOSE: In this study, we propose a system that combines a depth camera with a deep learning model for estimating the human skeleton and a depth camera to estimate the shooting part to be radiographed and to acquire the thickness of the subject, thereby providing optimized X-ray imaging conditions. METHODS: We propose a system that provides optimized X-ray imaging conditions by estimating the shooting part and measuring the thickness of the subject using an RGB camera and a depth camera. The system uses OpenPose, a posture estimation library, to estimate the shooting part. RESULTS: The recognition rate of the shooting part was 15.38% for the depth camera and 84.62% for the RGB camera at a distance of 100 cm, and 42.31% for the depth camera and 100% for the RGB camera at a distance of 120 cm. The measurement accuracy of the subject thickness was within ±10 mm except for a few cases, indicating that the X-ray imaging conditions were optimized for the subject thickness. CONCLUSION: The implementation of this system in an X-ray system is expected to enable automatic setting of X-ray imaging conditions. The system is also useful in preventing increased exposure dose due to excessive dose or decreased image quality due to insufficient dose caused by incorrect setting of X-ray imaging conditions.

Automated Quantitative Analysis of Anterior Segment Inflammation Using Swept-Source Anterior Segment Optical Coherence Tomography: A Pilot Study.

Background: The aim of this study is to develop an automated evaluation of anterior chamber (AC) cells in uveitis using anterior segment (AS) optical coherence tomography (OCT) images. Methods: We analyzed AS swept-source (SS)-OCT (CASIA 2) images of 31 patients (51 eyes) with uveitis using image analysis software (Python). An automated algorithm was developed to detect cellular spots corresponding to hyper-reflective spots in the AC, and the correlation with Standardization of Uveitis Nomenclature (SUN) grading AC cells score was evaluated. The approximated AC grading value was calculated based on the logarithmic approximation curve between the number of cellular spots and the SUN grading score. Results: Among 51 eyes, cellular spots were automatically segmented in 48 eyes, whereas three eyes (all SUN grading AC cells score: 4+) with severe fibrin formation in the AC were removed by the automated algorithm. The AC cellular spots increased with an increasing SUN grading score (p < 0.001). The 48 eyes were split into training data (26 eyes) and test data (22 eyes). There was a significant correlation between the SUN grading score and the number of cellular spots in 26 eyes (rho: 0.843, p < 0.001). There was a significant correlation between the SUN grading score and the approximated grading value of 22 eyes based on the logarithmic approximation curve (rho: 0.774, p < 0.001). Leave-one-out cross-validation analysis demonstrated a significant correlation between the SUN grading score and the approximated grading value of 48 eyes (rho: 0.748, p < 0.001). Conclusions: This automated anterior AC cell analysis using AS SS-OCT showed a significant correlation with clinical SUN grading scores and provided SUN AC grading values as a continuous variable. Our findings suggest that automated grading of AC cells could improve the accuracy of a quantitative assessment of AC inflammation using AS-OCT images and allow the objective and rapid evaluation of anterior segment inflammation in uveitis. Further investigations on a large scale are required to validate this quantitative measurement of anterior segment inflammation in uveitic eyes.

[Effect of Biweekly-DCF Neoadjuvant Chemotherapy on Skeletal Muscle Mass of Esophageal Cancer Patients].

INTRODUCTION: Several studies reported that skeletal muscle mass affects the clinical response and quality of life of cancer patients during chemotherapy. Here we examined the adverse events and effects of anticancer drugs on the skeletal muscle mass of patients with esophageal cancer who received biweekly docetaxel, cisplatin, and 5-fluorouracil(DCF)neoadjuvant chemotherapy in our department. SUBJECTS AND METHODS: We retrospectively analyzed 105 patients with esophageal cancer who received biweekly-DCF neoadjuvant chemotherapy in 2009-2019. The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on computed tomography was assessed to calculate the psoas muscle index(PMI). Patients were divided into the high PMI group(high-group)and low PMI group(low-group)by cut-off value(male: 6.36 cm2/m2; female: 3.92 cm2/m2). Hematological toxicity, non-hematological toxicity, and therapeutic effect were retrospectively examined. RESULTS: Male in the high-group had significantly less ≥Grade 3 hematological toxicity than those in the low-group. Univariate and multivariate analyses showed that PMI(odds ratio: 1, p<0.05)was significantly related to decreased hematological toxicity. CONCLUSION: In preoperative chemotherapy for esophageal cancer, the incidence of hematological toxicity was significantly higher in patients with low skeletal muscle mass. Thus, skeletal muscle mass may be a marker for determining optimal anticancer drug dosage.

Incorporation of virtual reality in the clinical training of medical students studying esophageal and mediastinal anatomy and surgery.

PURPOSE: To analyze the effectiveness of incorporating virtual reality (VR) in lectures on esophageal and mediastinal anatomy and surgical procedures for medical students at Gifu University during clinical training. METHODS: We divided medical students participating in clinical training, randomly, into two groups of 30 students each: those who received a lecture using 3D images (3D group) and those who received a lecture using VR images (VR group). Four days after the lecture, the students completed a written test to allow us to evaluate their comprehension, and a questionnaire on their opinion of the lectures. RESULTS: Based on the results of the written test, the VR group achieved better understanding of computed tomography (CT) images (p = 0.0001) and better interpretation of surgical images (p = 0.0163). However, there was no difference in the scores for spatial recognition and general problems. The questionnaire revealed that the VR group became more interested in mediastinal anatomy (p = 0.0165) and surgery (p = 0.0135). CONCLUSIONS: Our findings suggest that VR enhances the learning process. The lecture incorporating the VR experience was more effective than the traditional lecture for promoting an understanding of CT images and interpretation of surgical images; thus, it enhances the learning experience for medical students studying surgery.

Three-step operation for esophago-left bronchial fistula with respiratory failure after esophagectomy: a case report with literature review.

BACKGROUND: The development of esophago-bronchial fistula after esophagectomy and reconstruction using a posterior mediastinal gastric tube remains a rare complication associated with a high rate of mortality. CASE PRESENTATION: A 63-year-old man with esophageal cancer underwent a thoracoscopic esophagectomy with two-field lymph node dissection and reconstruction via a gastric tube through the posterior mediastinal route. Postoperatively, the patient developed extensive pyothorax in the right lung due to port site bleeding and hematoma infection. Four months after surgery, he developed an esophago-left bronchial fistula due to ischemia of the cervical esophagus and severe reflux esophagitis at the site of the anastomosis. Because of respiratory failure due to the esophago-bronchial fistula and the history of extensive right pyothorax, right thoracotomy and left one-lung ventilation were thought to be impossible, so we decided to perform the surgery in three-step systematically. First, we inserted a decompression catheter and feeding tube into the gastric tube as a gastrostomy and expected neovascularization to develop from the wall of the gastric tube through the anastomosis after this procedure. Second, 14 months after esophagectomy, we constructed an esophagostomy after confirming blood flow in the distal side of the cervical esophagus via gastric tube using intraoperative indocyanine green-guided blood flow evaluation. In the final step, we closed the esophagostomy and performed a cervical esophago-jejunal anastomosis to restore esophageal continuity using a pedicle jejunum in a Roux-en-Y anastomosis via a subcutaneous route. CONCLUSION: This three-step operation can be an effective procedure for patients with esophago-left bronchial fistula after esophagectomy, especially those with respiratory failure and difficulty in undergoing right thoracotomy with left one-lung ventilation.

Laparoscopic repair of femoral hernia involving the bladder with coexisting indirect inguinal hernia in a young man: a case report.

BACKGROUND: Bladder hernias are rare conditions that are difficult to diagnose preoperatively; many cases are diagnosed intraoperatively or postoperatively due to bladder injury. Most bladder hernias are direct inguinal hernias that involve the bladder in obese men older than 50 years old. We describe a rare case of a left femoral hernia involving the bladder in a young man. CASE PRESENTATION: A 32-year-old man with a bulge in the left inguinal region underwent laparoscopic transabdominal preperitoneal repair. Laparoscopy revealed a left indirect inguinal hernia. When the preperitoneal space was dissected toward the Retzius space along the vesicohypogastric fascia, the bladder was found to be protruding into the femoral ring and adhere to the hernial orifice severely. The bladder was reduced carefully without causing injury. After dissection, we repaired the left myopectineal orifice with a mesh. The patient was discharged on postoperative day 1 without complications. No recurrences or symptoms were noted at the 12-month follow-up. CONCLUSIONS: A femoral hernia involving the bladder in a young man is rare. This case demonstrated that dissection along anatomical landmarks is important for preventing injuries to the bladder because even young men may have bladder hernias.

Esophageal cancer with right vertebral artery variation observed during thoracoscopic esophagectomy: a case report.

BACKGROUND: Variation of the vertebral artery bifurcation is rare. This branching abnormality can cause unexpected vertebral artery damage and bleeding during thoracoscopic esophagectomy. There are few reports of abnormal branching of the vertebral artery associated with neurosurgery but none related to esophagectomy. We report the case together with the results of the evaluation of vertebral artery bifurcation and length in 50 patients with esophageal cancer in our hospital. CASE PRESENTATION: Thoracoscopic esophagectomy was performed on a 70-year-old patient with esophageal cancer. During lymph node dissection around the right reccurent laryngeal nerve, an unusual blood vessel was found running along the right subclavian artery. We determined this blood vessel to be the right vertebral artery branching far more centrally than usual. Because this anatomical abnormality was clarified, we could then recognize that the right reccurent laryngeal nerve coursed around the right vertebral artery and the right subclavian artery and thus was running in a larger arch than usual. CONCLUSION: Long right vertebral artery may appear in the surgical field of the thoracoscopic esophagectomy. Knowledge of such anatomical variation is important to prevent iatrogenic injury of the right vertebral artery and the right reccurent laryngeal nerve.

Comparison of Abiraterone and Combined Androgen Blockade Therapy for High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Propensity Score-Matched Analysis.

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score-matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2-89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

Subtotal stomach in esophageal reconstruction surgery achieves an anastomotic leakage rate of less than 1%.

Aim: The objective of this retrospective, single-institution study was to assess the safety and feasibility of reconstruction using subtotal stomach (SS) with esophagectomy for patients with esophageal cancer (EC). Although several different gastric-tube-making and anastomotic methods have been reported, the incidence rate of anastomotic leakage with EC surgery is generally reported over 10%. Complications should be avoided, and patient quality of life (QOL) should be maintained postoperatively. We have used SS reconstruction and hand-sutured cervical esophagus-subtotal gastric anastomosis at the neck wound in EC surgery. Short- and long-term outcomes in cases using SS are not well known. Methods: Between January 2008 and September 2019, 300 patients underwent esophagectomy for EC and reconstruction using SS. The primary endpoint was the rate of anastomotic leakage. Secondary endpoints were postoperative morbidities, QOL, and changes in patients' body weight and skeletal muscle weight. Results: Anastomotic leakage was observed in two patients (0.67%), and pneumonia was observed in nine patients (3.0%). Fifteen patients (5.0%) had an anastomotic stenosis requiring a bougie. Nausea occurred in 11 patients (3.7%), and dumping syndrome occurred in seven patients (2.3%). Dysphagia and early feeling of abdominal fullness scores tended to be high after surgery but gradually decreased after 6 months. Good results were obtained for reflux feeling scores. Body weight changed with an average decrease of -2 ± 3.71 kg (P = .071) over 5 years. Conclusion: Reconstruction using SS resulted in an extremely low rate of anastomotic leakage and good QOL postoperatively in patients with EC.

Holographic image-guided thoracoscopic surgery: possibility of usefulness for esophageal cancer patients with abnormal artery.

BACKGROUND: With the recent improvement of medical image analysis technology, three-dimensional (3D) holograms technology is beginning to be used as intraoperative image support. CASE PRESENTATION: We used a wearable holographic computer during thoracoscopic esophagectomy in a 70-year-old man with esophageal cancer. During lymph node dissection around the right recurrent laryngeal nerve, abnormal blood vessels were observed beside the right subclavian artery (RSA). As a result of confirming the anatomical variation of the right vertebral artery (RVA) using the 3D holograms, it was possible to understand that the RVA branched from a low position on the RSA. CONCLUSIONS: Holographic image-guided thoracoscopic esophagectomy using wearable holographic computer provided better spatial recognition of vascular variation and safe lymph node dissection.

Retinopathy Analysis Based on Deep Convolution Neural Network.

At medical checkups or mass screenings, the fundus examination is effective for early detection of systemic hypertension, arteriosclerosis, diabetic retinopathy, etc. In most cases, ophthalmologists and physicians grade retinal images by the condition of the blood vessels, lesions. However, human observation does not provide quantitative results, thus blood vessel analysis is an important process in determining hypertension and arteriosclerosis, quantitatively. This chapter describes the latest automated blood vessel extraction using the deep convolution neural network (DCNN). Diabetic retinopathy is a common cardiovascular disease and a major factor in blindness. Therefore, early detection of diabetic retinopathy is very important to preventing blindness. A microaneurysm is an initial sign of diabetic retinopathy, and much research has been conducted for microaneurysm detection. This chapter also describes diabetic retinopathy detection and automated microaneurysm detection using the DCNN.

Targeting castration-resistant prostate cancer with androgen receptor antisense oligonucleotide therapy.

Sustained therapeutic responses from traditional and next-generation antiandrogen therapies remain elusive in clinical practice due to inherent and/or acquired resistance resulting in persistent androgen receptor (AR) activity. Antisense oligonucleotides (ASO) have the ability to block target gene expression and associated protein products and provide an alternate treatment strategy for castration-resistant prostate cancer (CRPC). We demonstrate the efficacy and therapeutic potential of this approach with a Generation-2.5 ASO targeting the mouse AR in genetically engineered models of prostate cancer. Furthermore, reciprocal feedback between AR and PI3K/AKT signaling was circumvented using a combination approach of AR-ASO therapy with the potent pan-AKT inhibitor, AZD5363. This treatment strategy effectively improved treatment responses and prolonged survival in a clinically relevant mouse model of advanced CRPC. Thus, our data provide preclinical evidence to support a combination strategy of next-generation ASOs targeting AR in combination with AKT inhibition as a potentially beneficial treatment approach for CRPC.

[Ureteral Cancer Occuring in an Adult Megaureter : A Case Report].

A 86-year-old man visited our hospital to undergo a careful examination for asymptomatic gross hematuria. First, we performed cystoscopy and found a tumor projecting from the right ureteral orifice. We therefore performed computed tomography, which revealed right ureteral cancer projecting into the lower ureter and severe megaureter on bothsides. To evaluate the left megaureter, we performed retrograde pyelography, but were unable to insert a guide-wire. We therefore performed magnetic resonance-urography, which revealed an expanded left lower ureter, but no findings of hydronephrosis or any tumor lesions. Based on the findings of these examinations, we diagnosed the patient with right ureteral cancer with megaureter. Right nephroureterectomy and partial cystectomy were performed in April 2017. The pathological findings resulted in a diagnosis of invasive urothelial carcinoma. The patient experienced recurrence in his bladder at 3 months follow-up cystoscopy and underwent transurethral resection of bladder tumor.

HOXA10 expression profiling in prostate cancer.

BACKGROUND: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. METHODS: A meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa. RESULTS: A meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. CONCLUSIONS: Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.

Retinal biometrics based on Iterative Closest Point algorithm.

The pattern of blood vessels in the eye is unique to each person because it rarely changes over time. Therefore, it is well known that retinal blood vessels are useful for biometrics. This paper describes a biometrics method using the Jaccard similarity coefficient (JSC) based on blood vessel regions in retinal image pairs. The retinal image pairs were rough matched by the center of their optic discs. Moreover, the image pairs were aligned using the Iterative Closest Point algorithm based on detailed blood vessel skeletons. For registration, perspective transform was applied to the retinal images. Finally, the pairs were classified as either correct or incorrect using the JSC of the blood vessel region in the image pairs. The proposed method was applied to temporal retinal images, which were obtained in 2009 (695 images) and 2013 (87 images). The 87 images acquired in 2013 were all from persons already examined in 2009. The accuracy of the proposed method reached 100%.

Artery and vein diameter ratio measurement based on improvement of arteries and veins segmentation on retinal images.

Retinal arteriolar narrowing is decided based on the artery and vein diameter ratio (AVR). Previous methods segmented blood vessels and classified arteries and veins by color pixels in the centerlines of blood vessels. AVR was definitively determined through measurement of artery and vein diameters. However, this approach was not sufficient for cases with close contact between the artery of interest and an imposing vein. Here, an algorithm for AVR measurement via new classification of arteries and veins is proposed. In this algorithm, additional steps for an accurate segmentation of arteries and veins, which were not identified using the previous method, have been added to better identify major veins in the red channel of a color image. To identify major arteries, a decision tree with three features was used. As a result, all major veins and 90.9% of major arteries were correctly identified, and the absolute mean error in AVRs was 0.12. The proposed method will require further testing with a greater number of images of arteriolar narrowing before clinical application.

Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN-deficient of prostate cancer.

BACKGROUND: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naïve and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3ß and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.

Conditional PTEN-deficient mice as a prostate cancer chemoprevention model.

BACKGROUND: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). MATERIALS AND METHODS: Six-week-old mice were treated subcutaneously with 50 µg/g of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. RESULTS: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. CONCLUSIONS: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

Androgen deprivation induces phenotypic plasticity and promotes resistance to molecular targeted therapy in a PTEN-deficient mouse model of prostate cancer.

Castration-resistant prostate cancer is an incurable heterogeneous disease that is characterized by a complex multistep process involving different cellular and biochemical changes brought on by genetic and epigenetic alterations. These changes lead to the activation or overexpression of key survival pathways that also serve as potential therapeutic targets. Despite promising preclinical results, molecular targeted therapies aimed at such signaling pathways have so far been dismal. In the present study, we used a PTEN-deficient mouse model of prostate cancer to show that plasticity in castration-resistant tumors promotes therapeutic escape. Unlike castration-naïve tumors which depend on androgen receptor and PI3K/AKT signal activation for growth and survival, castration-resistant tumors undergo phenotypic plasticity leading to increased intratumoral heterogeneity. These tumors attain highly heterogeneous phenotypes that are characterized by cancer cells relying on alternate signal transduction pathways for growth and survival, such as mitogen-activated protein kinase and janus kinase/signal transducer and activator of transcription, and losing their dependence on PI3K signaling. These features thus enabled castration-resistant tumors to become insensitive to the therapeutic effects of PI3K/AKT targeted therapy. Overall, our findings provide evidence that androgen deprivation drives phenotypic plasticity in prostate cancer cells and implicate it as a crucial contributor to therapeutic resistance in castration-resistant prostate cancer. Therefore, incorporating intratumoral heterogeneity in a dynamic tumor model as a part of preclinical efficacy determination could improve prediction for response and provide better rationale for the development of more effective therapies.