Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide.

Androgen-deprivation therapy is a standard treatment for advanced prostate cancer. However, most patients eventually acquire resistance and progress to castration-resistant prostate cancer (CRPC). In this study, we established new CRPC cell lines, AILNCaP14 and AILNCaP15, from LNCaP cells under androgen-deprived conditions. Unlike most pre-existing CRPC cell lines, both cell lines expressed higher levels of androgen receptor (AR) and prostate-specific antigen (PSA) than parental LNCaP cells. Moreover, these cells exhibited primary resistance to enzalutamide. Since AR signaling plays a significant role in the development of CRPC, PSA promoter sequences fused with GFP were introduced into AILNCaP14 cells to conduct GFP fluorescence-based chemical screening. We identified flavopiridol, a broad-spectrum CDK inhibitor, as a candidate drug that could repress AR transactivation of CRPC cells, presumably through the inhibition of phosphorylation of AR on the serine 81 residue (pARSer81 ). Importantly, this broad-spectrum CDK inhibitor inhibited the proliferation of AILNCaP14 cells both in vitro and in vivo. Moreover, a newly developed liver metastatic model using AILNCaP15 cells revealed that the compound attenuated tumor growth of CRPC harboring highly metastatic properties. Finally, we developed a patient-derived xenograft (PDX) model of CRPC and DCaP CR from a patient presenting therapeutic resistance to enzalutamide, abiraterone, and docetaxel. Flavopiridol successfully suppressed the tumor growth of CRPC in this PDX model. Since ARSer81 was found to be phosphorylated in clinical CRPC samples, our data suggested that broad-spectrum CDK inhibitors might be a potent candidate drug for the treatment of CRPC, including those exhibiting primary resistance to enzalutamide.

Repeated ultrasound tests could be used to identify an isolated gastric duplication cyst before surgery.

A toddler girl was diagnosed with intra-abdominal simple cyst in the splenic flexure at the gestational period. Due to a severe fever that persisted for 6 days, she was admitted to the emergency room. The diagnosis of intraperitoneal cyst infection was made after contrast-enhanced CT revealed an enlarged cyst and a heterogeneous contrast effect on the cyst wall. A double-wall sign was observed on the cyst wall during continuous ultrasound follow-up, which led to the preoperative diagnosis of the cyst as a duplication cyst. The double-wall sign and cyst peristalsis were identified via successive ultrasound examinations to support the cyst diagnosis. Identifying a duplication cyst based solely on symptoms alone is difficult because the condition may present in different ways.

Efficacy and Tolerability of Second-line Pembrolizumab With Radiation Therapy in Advanced Urothelial Carcinoma.

BACKGROUND/AIM: Considering the limited data available on immune checkpoint inhibitors and radiation combination therapy in advanced urothelial carcinoma, this study evaluated the survival benefit and associated toxicity of adding radiation therapy to second-line pembrolizumab. PATIENTS AND METHODS: We retrospectively examined 24 consecutive patients with advanced bladder or upper urinary tract urothelial carcinoma and for whom second-line pembrolizumab was initiated between August 2018 and October 2021 in combination with radiation therapy (with curative intent in 12 patients, and palliative intent in 12 patients). Their survival outcomes and toxicities were compared with those of propensity-score-matched cohorts from a Japanese multicenter study with similar characteristics who received pembrolizumab monotherapy. RESULTS: The median follow-up periods after pembrolizumab initiation were 15 months for the curative cohort and 4 months for the palliative cohort. The median overall survival was 27.7 months for the curative cohort and 4.8 months for the palliative cohort. Compared with the matched pembrolizumab monotherapy cohort, overall survival was better among the curative cohort although not statistically significant (p=0.13), but similar between the palliative and matched pembrolizumab monotherapy cohorts (p=0.44). There was no difference in the incidence of grade ≥2 adverse events between the combination and monotherapy cohorts, irrespective of the intent of radiation therapy. CONCLUSION: The combination of radiation therapy and pembrolizumab can be performed with a clinically acceptable safety profile, and the addition of radiation therapy to immune checkpoint inhibitors may improve survival outcome after pembrolizumab treatment in cases where the intent of radiation therapy is curative.

Analysis of trifecta outcomes in a single center with robot-assisted partial nephrectomy for T1b renal tumors.

INTRODUCTION: This study was performed to investigate the preoperative factors associated with difficulty achieving trifecta in robot-assisted partial nephrectomy for clinical T1b renal cell carcinoma. METHODS: Among 187 patients who underwent robot-assisted partial nephrectomy at our hospital from March 2012 to February 2022, we retrospectively examined 30 patients with unilateral single clinical T1b renal cell carcinoma with at least 6 months of postoperative follow-up, excluding patients with hereditary disease. The following factors were examined in detail: patient-related factors, perioperative factors, surgical techniques, tumor factors, and R.E.N.A.L. nephrometry scores. We examined the preoperative factors associated with difficulty achieving trifecta. A positive surgical margin was pathologically defined as the presence of tumor cells at the margin of the resected specimen or visually defined as intraoperative tumor incision or pseudocapsular damage. RESULTS: Of the 30 patients in this study, 12 achieved trifecta and 18 did not. The reasons for not achieving trifecta were a warm ischemia time of >25 min (66.7%), positive surgical margin (23.3%), and Clavien-Dindo grade ≥3 complications (13.3%) (with overlapping factors). No patients had a pathologically positive surgical margin. Visually positive surgical margins were confirmed by the surgical records and surgical videos. Achieving trifecta was challenging in the multivariate analysis when the "L" component of the R.E.N.A.L. nephrometry score was ≥2 points. CONCLUSION: A preoperative "L" component of ≥2 points in the R.E.N.A.L. nephrometry score was associated with difficulty achieving trifecta.

Effect of continued perioperative antithrombotic therapy on bleeding outcomes following laparoscopic nephrectomy and nephroureterectomy.

INTRODUCTION: In this study, we aimed to assess the impact of perioperative continuation of antithrombotic therapy on bleeding and complications in patients undergoing laparoscopic radical nephrectomy (LRN) and nephroureterectomy (LNU). METHODS: This was a retrospective observational study. Patients who underwent LRN and LNU between January 2017 and July 2019 at our institution were recruited. All patients taking antithrombotic agents continued taking them during the perioperative phase (AA group). Surgical outcomes of patients in the AA group were compared with those of patients who were not taking antithrombotic agents (NA group). The primary outcome was the rate of bleeding complications. Secondary outcomes included intraoperative estimated blood loss, transfusion rate, and complications for up to 90 days. RESULTS: A total of 100 patients were included in the analysis, with 36 and 64 patients assigned to the AA and NA groups, respectively. Patients in the AA group were found to have more severe comorbidities than those in the NA group, with a Charlson Comorbidity Index ≥5, totaling 14 (39%) and 12 (19%), respectively (P = .03). According to surgical outcomes, none of the patients in the AA group required secondary procedures for bleeding complications. Moreover, there were no significant differences between the groups in intraoperative blood loss, hemoglobin deficit, rate of perioperative transfusion, readmission rate, or high-grade complications. DISCUSSION: These results indicate that perioperative use of antithrombotic agents does not increase the risk of bleeding and can be considered safe during LRN and LNU.

Advantages of monitoring rT3 and dividing LT3 dose in the treatment of consumptive hypothyroidism associated with infantile hepatic hemangioma.

OBJECTIVES: In consumptive hypothyroidism associated with infantile hepatic hemangiomas (IHH), elevated reverse triiodothyronine (rT3) is known due to elevated D3. This report shows that rT3 is a new indicator of IHH progression and that three divided doses of LT3 per day were more effective than a single dose. CASE PRESENTATION: A 23 day-old boy was diagnosed with diffuse IHH and severe hypothyroidism with high rT3. Propranolol and LT4 were administered. Hemangiomas gradually diminished and rT3 decreased, but the thyroid-stimulating hormone remained elevated, and free triiodothyronine (fT3) did not normalize after 2 weeks of treatment. Liothyronine (LT3) was started as a single dose and then divided into three doses after 1 week, which stabilized thyroid function. CONCLUSIONS: rT3 levels were less variable and decreased in conjunction with tumor shrinkage; thus, rT3 is an indicator of therapeutic outcomes for IHH. LT3 administered in divided doses aided in managing IHH-associated hypothyroidism.

Incomplete sagittal septum of the bladder with cystolithiasis.

Introduction: Incomplete sagittal septum of the urinary bladder is an extremely rare congenital anomaly and one of the variations in bladder duplication. Herein, we report a case of incomplete sagittal septum of the bladder with cystolithiasis. Case presentation: A 20-year-old man was referred to our department for examination and treatment of symptomatic cystolithiasis and a suspected giant ureterocele on the left side. Cystoscopy and urography performed under general anesthesia revealed anatomical structures suggestive of the sagittal septum of the bladder. Subsequently, transurethral septostomy and cystolithotripsy were performed. The detrusor muscle was microscopically identified, leading to the diagnosis of an incomplete sagittal septum of the bladder. Conclusion: Although extremely rare, an incomplete sagittal septum of the bladder may be difficult to differentiate from a ureterocele, and should be considered when a large cystic lesion is found in the bladder.

Development of Acute Inflammatory Demyelinating Polyneuropathy 11 Days after Spinal Surgery: A Case Report and Literature Review.

Guillain-Barré syndrome (GBS) usually has a good prognosis; however, patients may develop sequelae without prompt treatment. We herein describe an 81-year-old woman who developed acute-onset excruciating thigh pain and weakness in her lower extremities after spinal surgery. We diagnosed acute inflammatory demyelinating polyradiculoneuropathy by a nerve conduction study, which showed findings of demyelination without cerebrospinal fluid analysis because of a spinal prosthesis. Although anti-GM1 and anti-GalNAc-GD1a antibodies were positive, the patient was clinically diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (a subtype of GBS), not acute motor axonal neuropathy. She recovered well with immunoglobulin therapy. A literature review of 18 cases revealed that unexplained weakness, areflexia, and numbness of the extremities after spinal surgery, a shorter time from spinal surgery to symptom onset to general GBS, abnormal nerve conduction study results, normal spinal imaging findings, and the development of atypical symptoms such as cranial and autonomic nerve syndrome and respiratory failure are useful for diagnosing GBS when cerebrospinal fluid examination cannot be performed after spinal surgery.

Effect of Continued Perioperative Anticoagulant Therapy on Bleeding Outcomes Following Robot-assisted Radical Prostatectomy.

OBJECTIVE: To assess the impact of continued perioperative anticoagulant drug administration on bleeding and complications in patients undergoing robot-assisted radical prostatectomy. METHODS: Between January 2014 and January 2020, 620 patients with prostate cancer underwent robot-assisted radical prostatectomies and were retrospectively reviewed. Fourteen patients who discontinued antithrombotic therapy were excluded. Among the 606 included patients, 31 continued anticoagulant therapy during the perioperative phase (anticoagulant group). The anticoagulant group outcomes were compared with those of patients who continued clopidogrel and prasugrel (thienopyridine group = 13), aspirin monotherapy (aspirin group = 61), and no chronic antithrombotic agent (control group = 501). The primary outcome was the incidence of bleeding complications requiring transfusion, additional intervention, or readmission. Secondary outcomes were the incidence of thrombotic complications, estimated blood loss, and overall complication rates. RESULTS: Among the 31 patients in the anticoagulant group, 20 (65%) used directed oral anticoagulants, 11 (35%) used warfarin, and 5 used combined aspirin. Only 1 (3%) patient in the anticoagulant group required postoperative transfusion, and none required additional interventions or readmission. No significant differences were detected between the anticoagulant and other groups (anticoagulant vs thienopyridine, aspirin, and control groups) regarding bleeding complications (3% vs 8%, P = .51; 0%, P = .34; 0.4%, P = .17, respectively), thrombotic complications (3% vs 0%, P = .70; 2%, P = .56; 0.2%, P = .11, respectively), estimated blood loss (200 vs 100 mL, P = .63; 175 mL, P = .64; 165 mL, P = .74, respectively), or other high-grade complications (6% vs 0%, P = .49; 2%, P = .26; 3%, P = .24, respectively). CONCLUSION: Perioperative continuation of anticoagulant use is feasible for patients undergoing robot-assisted radical prostatectomy.

[A Case of Renal Oncocytosis with Bilateral Multiple Renal Masses].

A 63-year-old man with microscopic hematuria underwent contrast-enhanced CT, which showed multiple bilateral renal masses. Percutaneous biopsy results indicated renal oncocytosis. The tumors remained unchanged for 3 years. Renal oncocytosis is a very rare tumor, but it is an established disease entity characterized by numerous oncocytic tumors and diffuse (sporadic) renal parenchymal epithelial oncocytic changes on an analysis histopathology. Although renal oncocytosis can be sporadic or part of Birt-Hogg-Dube syndrome (BHDS), our case did not associate with BHDS because of absence of lung cyst.

[Evaluation of Lymphoceles by CT Scan Early after Robot-Assisted Radical Prostatectomy].

We report the incidence and characteristics of lymphoceles after robot-assisted radical prostatectomy (RARP). Computed tomography was performed on 79 patients one month after RARP or when symptoms appeared. The lymphocele was defined as a cystic lesion over 10 mm in diameter. Symptomatic and asymptomatic lymphoceles were identified in 25% (20/79) of all cases, and in 40.9% (18/44) of the cases with lymph node dissection (LND). Symptomatic lymphoceles were identified in 2.5% (2/79) of all cases. Lymphoceles were significantly associated with LND, pathological stage over T3, longer period of indwelling drain tube,and higher volume fluid of drain tube (p<0.05). In conclusion, lymphoceles are quiet common after RARP. However, they rarely become symptomatic.

[A Case of Chromophobe Renal Cell Carcinoma Associated with Birt-Hogg-Dubé Syndrome].

A 61-year-old man with a left renal mass, which was detected by ultrasound during a routine health examination, was referred to our department. The patient had a surgical history of two pneumothorax operations, and the patient's brother also had a history of pneumothorax surgery. A case of Birt-Hogg-Dubé (BHD) syndrome was suspected based on patient history. The pathological diagnosis of the resected tumor, which used robot-assisted laparoscopic partial nephrectomy, was determined to be chromophobe renal cell carcinoma (grade 2, pT1a). BHD syndrome was confirmed by genetic testing, where a nonsense mutation of exon 9 in the FOLLICULIN (FLCN) gene was detected. The patient is currently alive 10 months after surgery.

[Two Cases of Oncocytic Papillary Renal Cell Carcinoma].

Oncocytic papillary renal cell carcinoma isa variant of papillary renal cell carcinoma (PRCC). We herein report two cases treated with retroperitoneoscopic partial nephrectomy. Histologically, tumor cells of both cases exhibit round and regular nuclei with CK7 positive areas in the cytoplasm typical of TYPE1 PRCC and eosinophilic granular cytoplasm with E-cadherin positive areas in the cytoplasmic membrane, which indicates TYPE2 PRCC. Out of 46 cases reported in the literature, only one died of disease, which reveals its low malignant potential.

Proximal Junctional Failure After Long-Segment Instrumentation for Degenerative Lumbar Kyphosis With Ankylosing Spinal Disorder.

STUDY DESIGN: Case report. OBJECTIVE: We report a case of proximal junctional failure at the ankylosed, but not the mobile, junction after segmental instrumented fusion for degenerative lumbar kyphosis with ankylosing spinal disorder. SUMMARY OF BACKGROUND DATA: Proximal junctional failure (PJF) and proximal junctional kyphosis (PJK) are important complications that occur subsequent to long-segment instrumentation for correction of adult spinal deformity. Thus far, most studies have focused on the mobile junction as a site at which PJK/PJF can occur, and little is known about the relationship between PJK/PJF and ankylosing spinal disorders such as diffuse idiopathic skeletal hyperostosis. METHODS: The patient was an 82-year-old female with degenerative lumbar kyphosis. She had abnormal confluent hyperostosis in the anterior longitudinal ligaments from Th5 to Th10. The patient was treated operatively with spinal instrumented fusion from Th10 to the sacrum. RESULTS: Four weeks subsequent to initial surgery, the patient developed progressive lower extremity paresis caused by the uppermost instrumented vertebrae fracture (Th10) and adjacent subluxation (Th9). Extension of fusion to Th5 with decompression at Th9-Th10 was performed. However, the patient showed no improvement in neurological function. CONCLUSION: PJF can occur at the ankylosing site above the uppermost instrumented vertebrae after long-segment instrumentation for adult spinal deformity. PJF in the ankylosed spine may cause severe fracture instability and cord deficit. The ankylosed spine should be integrated into the objective determination of materials contributing to the appropriate selection of fusion levels. LEVEL OF EVIDENCE: 3.

Immediate Reduction of a Retro-odontoid Synovial Cyst Following Lateral Atlantoaxial Joint Puncture and Arthrography: A Case Report.

STUDY DESIGN: Case report. OBJECTIVE: We report on a case with a retro-odontoid synovial cyst, and the immediate reduction of the cyst was confirmed after lateral atlantoaxial joint puncture and arthrography. SUMMARY OF BACKGROUND DATA: Retro-odontoid synovial cysts are rare diseases located posteriorly to a dense axis. Because most reports have focused on surgical treatment, only a few have examined nonsurgical treatment. However, several months are required after nonsurgical treatment until cyst regression. METHODS: A 52-year-old female presented with atlantoaxial instability. She complained of neck pain and numbness in her hands. Magnetic resonance imaging revealed a retro-odontoid synovial cyst. Lateral atlantoaxial joint puncture and arthrography were performed. RESULTS: Two days after treatment, the patient showed significant improvement in the numbness of her hands, and a follow-up magnetic resonance imaging revealed an immediate reduction in the cyst. During a 4.5-year follow-up period, no recurrence of the clinical symptoms occurred. CONCLUSION: Lateral atlantoaxial joint puncture may immediately reduce retro-odontoid synovial cysts, and the lateral atlantoaxial joint has a communication channel with the retro-odontoid synovial cyst via the atlantodental joint. Once disappearance of the cyst is confirmed, an acceptable long-term outcome can be achieved with nonsurgical treatment even in cases with atlantoaxial instability. LEVEL OF EVIDENCE: N/A.

[A case of prostate carcinosarcoma successfully treated with combined modality therapy].

A 58-year-old man was referred to our hospital with dysuria and elevation of prostate specific antigen (38.0 ng/ml). Prostate surface was smooth and elastic hard on digital rectal examination. Transrectal ultrasound (TRUS) indicated irregular boundary and low echoic area of the prostate. Prostate biopsy specimen included the components of adenocarcinoma (Gleason score 9) and sarcoma. The tumor had extended to the rectum and metastasized to bilateral obturator lymph nodes and right ischial bone (cT4N1M1b). We started hormone therapy for the adenocarcinoma component followed by total pelvic exenteration with colostomy and ileal conduit diversion for the sarcoma component. In addition, pelvic cavity and the bone metastasis were irradiated. The patient was free of recurrence at four and a half years after surgery.

[Experience of transobturator sling for iatrogenic male stress urinary incontinence].

We performed transobturator sling (TOS) surgery for iatrogenic stress urinary incontinence (SUI) in 7 men. Assessment with the International Consultation Society Incontinence Questionnaire Short Form revealed that complete continence, significant improvement, and no change of incontinent status were observed in two, three, and two patients, respectively, at one year after surgery. Of the three patients with significant improvement, two patients obtained a pad-free status. Both of the two patients without improvement had a past history of salvage radiation therapy for biochemical recurrence after radical prostatectomy before TOS surgery. The severity of SUI seems not to be associated with the outcome of TOS surgery. TOS surgery can be one of the surgical options for iatrogenic male SUI.

Postoperative deep surgical-site infection after instrumented spinal surgery: a multicenter study.

A retrospective survey revealed 37 cases (1.1%) of deep surgical-site infection (SSI) among 3,462 instrumented spinal surgeries between 2004 and 2008. Excluding 8 patients who were unclassifiable, we categorized 29 patients into 3 groups of similar backgrounds-thoracolumbar degenerative disease (the DEG group; n = 15), osteoporotic vertebral collapse (the OVC group; n = 10), and cervical disorders (the cervical group; n = 4)-and investigated the key to implant salvage. Final respective implant retention rates for the groups were 40, 0, and 100%, with the OVC group having the worst rate (p < 0.01). In the DEG group with early infection, those whose implants were retained had lower body temperatures, lower white blood cell counts, and a lower rate of discharge at the time of SSI diagnosis (p < 0.05). Implant retention may be affected by initial spinal pathology. In the DEG group, debridement before drainage may be advantageous to implant salvage.

Urinary retention in a female patient caused by a urethral venous thrombus with massive edema.

Female urinary retention is rarely caused by an unknown condition. In such a case, common causes including neurogenic, anatomical, traumatic and iatrogenic voiding dysfunction are excluded. Both the radiological and histological findings specific to the condition remain unclear. We herein report a 75-year-old woman in whom a large venous mass and massive edema at the proximal urethra caused urinary outlet obstruction based on magnetic resonance images and histological findings. Ultrasonography and cystoscopy showed a urethral mass lesion protruding into the bladder neck. Fat-suppressed T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance images suggested thrombosed veins with massive edema under the urethral mucosa. Transurethral resection of the mass lesion was carried out, and histopathological analysis proved the presence of thrombosed large veins. The patient regained normal urination, and the mass lesion did not recur. Thrombosed venous mass with edema at the proximal urethra might be an important cause of atypical urinary retention in women.