The Ser/Thr-specific kinase, polo-like kinase 1 (Plk1), is a crucial eukaryotic cell cycle regulatory protein. Overexpression of this kinase is observed in many cancer cells and where it can be related to their aggressiveness. Dysfunction of Plk1 in cancer cells causes mitotic arrest and subsequent apoptosis. Accordingly, Plk1 is considered as a target for the development of anti-cancer agents. Plk1 has two domains, a catalytic kinase domain (KD) and a polo-box domain (PBD). PBD intramolecularly interacts with its KD and regulates Plk1 activity and localization. Therefore, in addition to the KD, the PBD is considered to be a potential drug target. We have been developing peptidic low-nanomolar-affinity PBD-binding inhibitors. However, these peptides do not show significant cytotoxicity, due to their low cell membrane permeability. To obtain cell-active Plk1 inhibitors, I applied a bivalent approach designed to simultaneously engage both KD and PBD regions of Plk1 for enhancing the potency, selectivity and lipophilicity. Here, I developed bivalent Plk1 inhibitors, in which the PBD-binding peptides are conjugated with the known KD-binding inhibitors BI2536 or wortmannin using PEG linkers. These bivalent inhibitors exhibit up to 100-fold enhanced Plk1 affinity relative to the best monovalent PBD-binding ligands, higher selectivity for tested kinases compared to BI2536, and significant cytotoxicity against HeLa cells.

The development of dual energy CT (DECT) has made it possible to provide not only morphological characteristics but also a wide range of quantitative information. The purpose of this study is to differentiate between benign and malignant solitary pulmonary nodules (SPN) by using electron density values obtained from DECT.

There are attempts to assess tumor heterogeneity by texture analysis. However, the ordered subsets-expectation maximization (OSEM) reconstruction method has problems depicting heterogeneities. The aim of this study was to identify image reconstruction parameters that improve the ability to depict internal tumor necrosis using a self-made phantom that simulates internal necrosis.

A 70-years-old man with metastatic hormone-sensitive prostate cancer received the apalutamide, an oral androgen receptor signaling inhibitor. On day10 after drug initiation, fever and skin rash appeared on his whole-body surface. He stopped taking the drug on day18 and skin symptoms temporarily improved about 7 days after discontinuation. However, on day 38, symptoms recurred, and the patient was admitted to the hospital as an emergency due to suspicion of Stevens-Johnson syndrome. Steroid pulse therapy was administered, and gradual improvement of the skin lesions was observed. With the widespread use of apalutamide in daily clinical settings, severe drug eruptions such as the present case may potentially increase, and further additive experiences are awaited.

A 35-year-old man visited a local doctor for continuing analysis of his infertility. Semen analysis revealed azoospermia while an ultrasonography detected a right testicular tumor with a diameter of 10 mm. A blood test was negative for tumor markers. Magnetic resonance imaging showed a 1-cm tumor in the right testis and atrophy of the left testis. A testicular tumor arising from a functional unilateral testis was discovered during infertility treatment for which the patient was referred to our hospital for fertility preservation. Right and left testicular volumes were 18 mL and 3 mL, respectively, and his serum testosterone level was 2.96 ng/mL. Noting the atrophy of the contralateral testicle, we proceeded with a rapid pathology diagnosis by partial testicular resection. If no evidence of tumor malignancy was found, the surgery would have been concluded with no further dissection. Since the patient was undergoing fertility treatment, the decision was made to take sperm from the extracted testicle to preserve his fertility, followed by orchiectomy. Because a seminoma was suspected through the rapid pathological diagnosis, the man eventually underwent higher orchiectomy and testicular sperm extraction. The final diagnosis was seminoma, followed by successful retrieval of a sufficient level of sperm. Post operative serum testosterone level was found to be 0.32 ng/mL, after which testosterone replacement therapy was introduced. Through rapid diagnosis of pathology, successful management and outcome were achieved in the case of testicular cancer combined with infertility.

We report the case of a 41-year-old man who presented with gross hematuria and a bladder tumor on ultrasonography. Magnetic resonance imaging indicated a possible muscle-invasive bladder cancer or urachal carcinoma. Following transurethral resection of the bladder tumor, histopathological findings revealed an adenocarcinoma similar to colorectal cancer. The patient was diagnosed with an urachal carcinoma in the urinary bladder dome. Since multiple lung metastases were observed on computed tomography, and his serum carcinoembryonic antigen level was 116 ng/dL, his final diagnosis was a stage IVb urachal carcinoma. He received 11 courses of mFOLOX6, and underwent a laparoscopy-assisted partial cystectomy and pelvic lymph node dissection. Pathological examination confirmed negative surgical margins, but remained tumor cells were confirmed. The patient continued mFOLFOX6 treatment for 12 months postoperatively, with no disease progression observed.

(Objective) This study aimed at evaluating the efficacy and safety of upfront docetaxel (DTX) treatment and androgen deprivation therapy (ADT) in male patients with high-volume metastatic castration-sensitive prostate cancer (HV-mCSPC). (Methods) This retrospective study was conducted using the medical records of 30 patients treated for HV-mCSPC by using upfront DTX treatment along with ADT at Atsugi City Hospital between December 2015 and December 2022. The patient characteristics, demographics, oncological outcomes, adverse events, and sequential therapy were evaluated. (Results) Thirty patients were included in the final analysis. The median patient age and prostate-specific antigen at diagnosis were 73 years (range, 53-83 years) and 250 mg/ml (range, 0.54-3,817 ng/ml), respectively. The completion rate of six cycles of upfront DTX treatment was 86.7%. The median progression-free survival was 24 months; the median overall survival was not reached, and the 5-year survival rate was 71.5%. Alopecia was the most frequent non-hematological adverse event (60%) followed by fatigue (53.3%). Overall, adverse events of grade 3 or higher occurred in 46.7% of the patients, with neutropenia being the most frequent. The incidence of neutropenia of grade 3 or higher was significantly lower in the group receiving primary prophylaxis with long-acting granulocyte colony-stimulating factor (7.7% vs. 75%, P = 0.009). Abiraterone was the most frequently administered sequential treatment in 12 patients (60%). (Conclusion) In the triplet combination treatment era, upfront DTX treatment and ADT for patients with HV-mCSPC was safe as primary prophylaxis for severe neutropenia and effective as an upfront treatment. However, it should be selected if its effectiveness is superior to triplet treatment considering adverse events, cost-effectiveness, and quality of life.

(Purpose) We performed a clinical retrospective study on the evaluation of pembrolizumab treatment results for advanced urothelial cancer in our hospital. (Materials and Methods) Twenty-seven patients diagnosed with advanced or metastatic urothelial carcinoma who received pembrolizumab between April 2018 and December 2021 were included. We retrospectively reviewed medical records to examine treatment outcomes, immune-related adverse event (irAE), and prognostic factors. (Results) The median age of patients was 76 years, and the median number of pembrolizumab doses was 6. The median overall survival was 8.8 months, and the best treatment response according to RECIST version 1.1 was complete response 1, partial response 7, stable disease 5, and progression disease 14. Pre-pembrolizumab risk factors related to overall survival include the presence of liver metastasis, LDH ≥200 IU/L, and TSH <4 μIU/mL in univariate analysis. Grade 3 irAE was type 1 diabetes in only 1 case, and grade 2 were hypothyroidism in 4 cases, type 1 diabetes in 1 case, interstitial pneumonia in 1 case, and skin disorder in 1 case. Nine patients had a TSH of 4 μIU/mL or higher at the start of pembrolizumab, and four of them had hypothyroidism requiring oral levothyroxine, and none of the patients in the low TSH group required hormone replacement (p =0.013). (Conclusion) High TSH level before pembrolizumab administration for advanced urothelial cancer was associated with hypothyroidism, suggesting the possibility of improved prognosis.

An 82-year-old woman previously underwent cystectomy and ureterocutaneous ureteral fistula for bacillus calmette guerin-resistant bladder cancer at the age of 70 years old in February 2012. Pathological examination revealed a pTisN0. In October 2020, the patient experienced vulvar itching and pain, which prompted her to consult a gynecologist. Vulvovaginitis was diagnosed, and the patient was observed. However, in June 2023, the vulvar itching persisted, prompting a biopsy for refractory erosions of the vulva. Paget cells were identified in the epidermis, and immunostaining (CK7 (＋), CK20 (＋), p63 (＋), GATA3 (＋), and GCDFP15 (-)) was used to diagnose secondary extramammary Paget's disease due to urothelial carcinoma. Magnetic resonance imaging revealed a 25 mm mass in the pelvic floor, and a biopsy showed the same immunostaining pattern as the skin lesion. Consequently, a diagnosis of local recurrence 11 years after cystectomy and associated secondary extramammary Paget's disease was established. Owing to the evidence of invasion of the mass into the levator ani muscle, she underwent laparoscopic rectal resection plus combined resection of the tumor, perineum, and levator ani muscle in October. Currently, she is 3 months postoperatively without evidence of recurrence.

A 50-year-old woman presented to our hospital in May2021 with a fever of approximately39 °C and abdominal pain. A contrast-enhanced computed tomography (CT) scan revealed an 88 mm right renal tumor. Two weeks later, a follow-up CT scan demonstrated rapid tumor growth, with the major axis measuring 100 mm. During this interval, her abdominal pain worsened, and she developed lower leg edema. A contrast-enhanced CT scan conducted 5 days before the scheduled surgery, four weeks after initial presentation, showed further tumor progression, with a diameter of 155 mm. The tumor, which had infiltrated the ascending colon, duodenum, liver, gallbladder, and inferior vena cava (IVC), was surgically removed along with the right kidney. Due to its complexity, the planned wide excision was deemed infeasible. Therefore, a tumor resection was performed macroscopically. Histopathological examination confirmed the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Subsequently, the patient experienced a postoperative tumor recurrence. Although the patient received doxorubicin chemotherapy, she passed away5 weeks after the operation. This case highlights the critical importance of prompt surgical excision with adequate tumor margins in the management of UPS.

With the ageing of the population in Japan, an increasing number of elderly prostate cancer patients will require treatment. However, the elderly often have comorbidities, which can make treatment decisions for prostate cancer patients difficult. Therefore, we investigated prostate cancer deaths and risk factors among patients aged 80 years or older at diagnosis of prostate cancer at our hospital. Of 532 prostate cancer cases diagnosed and treated at our hospital between January2011 and December 2018, 90 cases were included. The median observation period was 54 months and 13 (14.4%) patients died of prostate cancer. The overall 5-year cancer-specific survival rate was 86.7%, with M1 (47.1%) and GS≥9 (71.9%) as significant risk factors on multivariate analysis. Patients with metastatic prostate cancer, even those older than 80 years, should be cautiously started on treatment after explaining to the patient and family that the chance of prostate cancer death is not low. Even in patients with localized prostate cancer, four out of 45 (8.9%) high-risk prostate cancer patients died of prostate cancer, suggesting that curative treatment is an option, depending on their life expectancy.

A 65-year-old man with dysuria was referred to our department with a prostate-specific antigen concentration of 145.6 ng/ml. Unenhanced T2-weighted magnetic resonance imaging showed high signal intensity mainly in the right lobe of the prostate and a mass lesion with a mucus component. Contrastenhanced magnetic resonance imaging showed a progressively increasing contrast effect in the same region. Prostatic biopsy was performed, and histopathology revealed a Gleason score of 4＋3＝7, and a diagnosis of mucinous carcinoma of the prostate, stage cT3bN0M0. The patient underwent robot-assisted laparoscopic total prostatectomy and enlarged lymph node dissection. Pathological analysis confirmed mucinous adenocarcinoma of the prostate, with a Gleason score of 4＋3＝7, EPE1, RM0, ly1, v0, pn1, sv0, n1 (1/22). The final pathological diagnosis was prostate mucinous carcinoma, pT3aN1M0, and strict post-operative two-year follow-up resulted in no biochemical recurrence (prostate-specific antigen concentration was 0.001 ng/ml). The results suggest that surgical treatment may provide a good prognosis in high-risk prostatic mucous carcinoma.

A 68-year-old male was referred to our hospital because plain computed tomography (CT) showed right hydronephrosis. Contrast-enhanced CT revealed a mass with an irregular margin and poor contrast effect in the lower pole of the right kidney, which invaded the perirenal fat tissues and the area around the inferior vena cava (IVC). Moreover, a thrombus extending from the right renal vein to the IVC was detected, some of which was suggestive of tumor components on contrast-enhanced magnetic resonance imaging (MRI). Biopsy of the renal pelvic mucosa revealed urothelial carcinoma, which was diagnosed as cT4N0M0 renal pelvic cancer. After five courses of neoadjuvant chemotherapy with gemcitabine plus carboplatin, the patient underwent right nephroureterectomy. To avoid tumor cell dissemination into the abdominal cavity, we removed the thrombus and a portion of the IVC were removed en bloc with the right kidney without opening the vein. On pathological diagnosis, the renal tumor was identified as high-grade urothelial carcinoma with sarcomatoid features and squamous differentiation. The tumor invaded the IVC wall through perirenal fat tissues and further developed into a mass in the lumen of the vein. Although the patient was treated with nivolumab as a postoperative adjuvant therapy, he developed liver metastases and local recurrence on the right psoas muscle 6 months after surgery and is currently receiving chemotherapy with enfortumab vedotin.

A 74-year-old woman with no history of trauma visited our hospital with right-sided abdominal pain and general malaise. Blood tests revealed elevated inflammatory markers. A computed tomography (CT) scan revealed a 8 cm mass and subcapsular hematoma on the lower pole side of the right kidney. She was diagnosed with a malignant tumor or renal abscess combined with subcapsular hematoma and inflammation and was treated conservatively with antibiotics. The symptoms quickly improved. Although kidney biopsy was performed, no obvious malignant cells were found. Since a subsequent CT scan could not exclude the possibility of kidney cancer, radical nephrectomy was performed. The histopathological diagnosis was clear cell renal cell carcinoma. She has not experienced recurrence within 10 months after the surgery. Clear cell renal cell carcinoma combined with subcapsular blood is relatively uncommon and can be difficult to diagnose, requiring careful decision-making regarding treatment indications.

We report a case of retroperitoneal abscess mimicking a malignant retroperitoneal tumor. A 77-yearold woman was referred to our hospital because of retroperitoneal tumor without any symptoms. The tumor was located just behind the inferior vena cava, and the tumor size was about 38 mm. The tumor showed no abnormal findings in positron emission tomography (PET) and 123I-MIBG scintigraphy. We considered the tumor as benign tumor or retroperitoneal cyst. Follow-up computed tomography (CT) 6 months after the first visit to our department showed no change in the tumor. However, 3months later, she presented with fever, general fatigue and back pain. CT scan at that time showed that the tumor had enlarged to about 70 mm, and the tumor seemed to have invaded into the inferior vena cava. Thrombus into the inferior vena cava was also found. These findings were suggestive of malignancy, so we decided to remove the tumor. During the operation, the tumor was removed together with the inferior vena cava and right kidney because of severe adhesion. The pathological diagnosis was retroperitoneal abscess. Retroperitoneal abscess is caused by various reasons including diabetes mellitus, steroid use, inflammatory disease of gastrointestinal tract and retroperitoneal organs. Although the etiology was unknown in the present case, acute infection of the preexisting retroperitoneal cyst was a possible cause.

Metanephric adenoma is an extremely rare disease. We describe two cases of metanephric adenoma. Case 1 : A 17-year-old male adolescent developed gross hematuria, and urinalysis revealed positive protein and occult blood. He was referred to our department for further evaluation and likely tumor removal. Contrast-enhanced computed tomography (CT) showed a neoplasm (23 mm) with poor contrast effect during the early as well as the late contrast phase. Case 2 : A 61-year-old woman presented with an incidentally detected tumor in the lower pole of the right kidney ; contrast-enhanced CT revealed a large neoplasm (10 mm) with poor contrast effect during the early as well as late contrast phase. Both patients underwent robot-assisted partial nephrectomy (RAPN) under the preoperative diagnosis of papillary renal cell carcinoma. Metanephric adenoma is histopathologically indistinguishable from papillary renal cell carcinoma preoperatively, and histopathology and immunostaining are neceaasry for accurate diasnosis.

TA 51-year-old Japanese man presented with a history of percutaneous transhepatic portal veinembolization, right hepatic lobectomy for hepatocellular carcinoma, and left upper pulmonary lobectomy forpulmonary metastasis of hepatocellular carcinoma. Owing to the elevated tumor marker levels,ultrasonography and fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PETCT) were performed, which revealed a left renal tumor 24 mm in diameter with FDG accumulation ;accordingly, renal metastasis of hepatocellular carcinoma was diagnosed. Localized radiofrequencyablation (RFA) was scheduled due to the absence of metastases other than that in the left kidney. The tumorcould not be effectively visualized using ultrasonography immediately before RFA ; therefore, a CT scan wasperformed. CT revealed a hematoma around the left kidney resulting from the spontaneous rupture of a leftrenal tumor ; consequently, RFA was discontinued. A left nephrectomy was performed for radicaltreatment of the left renal tumor. The pathological diagnosis of the resected specimen was left renalmetastasis of hepatocellular carcinoma. This is the third reported case in Japan of spontaneous rupture of ametastatic renal tumor from hepatocellular carcinoma.

There is a riskof positive resection margins (RMs) in patients who had undergone robot-assisted laparoscopic radical prostatectomy (RARP) following systematic prostate biopsies. This study examined the riskof positive RM post-RARP when magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy was performed along with systematic prostate biopsy. Sixty-one patients who had undergone MRI fusion biopsy and systematic transrectal and transperineal biopsies, followed by RARP, at our hospital between September 2020 and October 2023 were included. The median age was 61 years, and the median PSA level was 8.4 ng/ml. Although there was no significant difference between the two groups, the RM-positive group exhibited a significantly higher clinical stage. Of the 122 lobes of the prostate (including the right and left lobes), the RM-positive group (26 lobes) had a significantly higher proportion of positive transrectal biopsies of the internal and external glands of the 61 cases. Additionally, in the RM-positive group, the proportion of positive transperineal biopsies of the internal glands and the ratio of positive systematic biopsies were significantly higher. Logistic regression analysis of riskfactors linked to increased RM-positivity revealed that neurovascular bundle (NVB) preservation and positive target biopsy were not significant variables. However, systematic biopsies positivity rate was a significant riskfactor. Thus, the riskof RMpositivity was shown to be associated with the systematic biopsy positivity rate, which suggested that systematic biopsies may be necessary for evaluating the indications for NVB preservation.

Recent advances in medical and nursing care have improved the prognosis of patients with severe motor and intellectual disabilities (SMID). However,there has been a proportionate increase in the incidence of malignant tumor-related deaths in this population owing to their prolonged survival. In this study,we reviewed the clinical characteristics of four bladder cancers in young SMID patients treated at our hospital. In all patients,a diagnosis of a bladder tumor was made after a referral from the family medical department to the urology department ; the median time from the first symptom to the diagnosis was 12.5 months (range : 0-17 months). In clinical staging,two patients had non-invasive cancer,while the other two had invasive bladder cancer (one patient with cN1). Radical cystectomy with ileal conduit was performed in three patients (pathological stages were pTa with CIS,pT3aN1,and pT3bN0),and transurethral bladder tumor ablation was performed in the fourth one. The median postoperative follow-up period was 134 months (range : 20-182 months). Three patients survived afterward,while one patient died due to other causes. These findings suggest that young SMID patients tend to have a more severe form of bladder cancer compared to the general young population. Therefore,complaints of gross hematuria and urinary symptoms in young patients with SMID need appropriate evaluation in cooperation with the family department for an early diagnosis.

A 75-year-old woman had suffered from intermittent gross hematuria. Ultrasonography, enhanced CT, cystoscopy and urinary cytology had no abnormal findings. Four months later, antibiotics were administered for recurrent gross hematuria and urinary frequency, and not effective. Then, a subcutaneous masson her buttock wasfound to be rapidly growing. The tumor waspathologically diagnosed asan adenocarcinoma by surgical resection. One month later, she had lower abdominal pain and the enhanced CT examination revealed right renal pelvic tumor. Laparoscopic nephroureterectomy was performed and the pathological diagnosiswaspoorly differentiated urothelial carcinoma with adenocarcinoma differentiation. Under the immunohistochemical analyses, the patient was diagnosed with renal pelvic tumor with subcutaneous metastasis. Chemotherapy was not effective for the rapid metastasis throughout the body, and the patient died 4 monthsafter the surgery.