A 70-year-old man with prostate cancer (cT3aN0M0), with a prostate-specific antigen (PSA) level of 38.9 ng/mL, and a Gleason score of 4+4 = 8, was treated with maximum androgen blockade for 1 year, resulting in a PSA reduction to 0.1 ng/mL. He subsequently underwent robot-assisted laparoscopic radical prostatectomy (RARP). Pathological examination revealed pT3bN1with negative surgical margins. Postoperatively, without additional treatment, PSA levels were 0.007 ng/mL and 0.019 ng/mL at 2 and 5 months, respectively. Six months after surgery, the patient developed left hydronephrosis with upper ureteral urine leakage but no signs of ureteral cancer. However, PSA slightly increased to 0.055 ng/mL, whereas carcinoembryonic antigen (CEA) levels increased to 19.2 ng/mL. Despite this, gastro-colonoscopy failed to detect any evidence of cancer. Nine months after surgery, multiple lung tumors, a solitary hepatic tumor, intraperitoneal lymphatic swellings, and port site masses were identified. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan did not reveal any other malignancies. At that time point, PSA increased to 0.185 ng/mL, while neuron-specific enolase and pro-gastrin-releasing peptides levels were within normal limits. Subsequent gastro-colonoscopy did not detect any malignancies. Ten months after surgery, bilateral orchiectomy and docetaxel chemotherapy were initiated for recurrent prostate cancer with aggressive variants but without neuroendocrine differentiation. Immunohistochemistry (IHC) of a biopsy sample from the port site mass suggested enteric adenocarcinoma distinct from the prostatic tissue observed in the original RARP specimen. The metastases progressed, and CEA levels continued to rise despite three cycles of docetaxel chemotherapy. Genomic testing identified KRAS and other mutations, confirming the tumor's compatibility with enteric adenocarcinoma. Fourteen months after surgery, chemotherapy for colon cancer was initiated. Unfortunately, the patient succumbed to respiratory failure 19 months after surgery. In cases of unusual recurrence patterns, as observed in this case, IHC and genomic testing of the recurrent mass can be crucial for accurate diagnosis.

We performed robot-assisted radical prostatectomy (RARP) for 221 patients from December 2015 to May 2023. In 218 patients, the prostatic anterior fat pad was submitted separately for histopathological evaluation. Fourteen patients (6.4%) had lymph nodes in the prostatic anterior fat pad, and three (1.4%) had lymph node metastasis in the prostatic anterior fat pad. The details of three cases are presented here.Case 1 was a 63-year-old patient who underwent RARP for prostate cancer (cT2aN0M0), with an initial prostate-specific antigen (PSA) concentration of 24.522 ng/ml and a Gleason score of 3+4. The pathological results indicated adenocarcinoma, pT3a, Gleason score: 3+4. The postoperative PSA nadir was 0.205 ng/ml, and the patient was diagnosed with biochemical recurrence. Subsequently, the patient underwent hormone therapy and salvage radiation therapy, with no recurrence to date.Case 2 was a 62-year-old patient who underwent RARP for prostate cancer (cT2aN0M0), with an initial PSA of 10.418 ng/ml and a Gleason score of 4+4. The pathological results indicated adenocarcinoma, pT2c, Gleason score: 4+4. The postoperative PSA nadir was 0.401 ng/ml, and the patient was diagnosed with biochemical recurrence. The patient subsequently underwent hormone therapy.Case 3 was a 76-year-old patient who underwent RARP for prostate cancer (cT2aN0M0), with an initial PSA of 4.676 ng/ml and a Gleason score of 4+3. The pathological results indicated adenocarcinoma, pT2c, Gleason score: 3+4. The postoperative PSA nadir was 0.031 ng/ml, and the patient has not experienced recurrence to date.

(Objective) Patient characteristics and treatment outcomes of a rare histologic type of bladder neuroendocrine carcinoma were evaluated. (Methods) 2,133 cases of bladder cancer treated by transurethral resection of bladder tumor from August 2005 to August 2022 were histopathologically reevaluated, and clinicopathological factors, treatment methods, and prognosis of cases with a confirmed diagnosis of bladder neuroendocrine cancer were analyzed. (Results) Of 2,133 cases, 12 (0.56%) were diagnosed as neuroendocrine carcinoma. Immunohistochemical staining revealed small cell carcinoma in 10 cases (83.3%) and large cell carcinoma in 2 cases (16.7%). The median age was 79 years, and performance status 2 or higher was reported in 3 cases. Seven cases had localized cancer at the time of diagnosis, five cases had distant metastasis, and radical cystectomy was performed in four cases. Of the 3 cases who received chemotherapy, first-line platinum-based chemotherapy achieved disease control in two cases. After second-line treatment, no cases responded to pembrolizumab or enfortumab vedotin. The median overall survival (OS) of all cases was 12.5 months. The median OS of cases who underwent total cystectomy was 26 months, and that of cases who did not undergo total cystectomy was 8.2 months, showing a significant difference (p=0.05). (Conclusion) Neuroendocrine carcinoma of the urinary bladder often develops in older patients and has a poor prognosis. In cases of localized cancer, total cystectomy should be performed if possible.

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.

Epidermoid cysts originating from the upper urinary tract are extremely rare, and only five cases have been reported previously. We report a rare case of epidermoid cyst that originated from the right ureter : A 76-year-old man presented with asymptomatic gross hematuria. Computed tomography showed a right ureteral tumor (14×8 mm in size). Retrograde pyelography showed a defect (14 mm diameter) of the contrast medium in the same region. Urinary cytological examination indicated class III. A ureteral tumor was clinically indicated, and retroperitoneoscopic-assisted radical nephroureterectomy was performed. Postoperative histopathological examination of the resected specimen showed ureteral epidermoid cysts without any malignancy.

Ganglioneuroma, an infrequent benign tumor that originates from the sympathetic nervous system, is usually a solitary occurrence and rarely occurs at multiple sites. Here, we report a case of retroperitoneal ganglioneuroma with multifocal bone involvement in a middle-aged woman. A 43-year-old female was incidentally diagnosed with a retroperitoneal tumor on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a retroperitoneal tumor that was 11 cm in diameter above her left kidney and multiple bone lesions. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed a slightly high FDG uptake (standardized uptake value (SUV) max, 3.7) in the retroperitoneal mass and mild accumulation in the L1 vertebral body, zygoma, acetabulum, and calcaneus. Biopsies were performed for the retroperitoneal and lumbar spine tumors, both of which were diagnosed as ganglioneuromas. Total surgical resection is the standard treatment of this condition ; however, for this patient, it was difficult to remove all the tumors, and the ganglioneuromas generally followed a benign course. Therefore, a watchful waiting approach was chosen and no tumor growth was observed three years after her first visit to our hospital.

We report a case of testicular cancer after kidney transplantation in a 29-year-old man. Twenty-two years after the surgery, computed tomography (CT) showed a retroperitoneal mass 3 cm in diameter. Positron emission tomography (PET) -CT revealed high FDG uptake in both the right testis and retroperitoneal mass. Regarding serum tumor markers, α fetoprotein (AFP) was slightly elevated to 12.5 ng/ml. He underwent right radical orchiectomy, and pathological examination revealed pure seminoma. After surgery, the serum AFP level remained high (12. 9 ng/ml), and we initially considered this nonseminoma patient to have a good prognosis according to International Germ Cell Consensus Classification. During three cycles of a combination regimen including bleomycin, etoposide, and cisplatin (BEP), we performed adjustment of immunosuppressive therapy, treatment for Cytomegalovirus infection (valganciclovir hydrochloride), and that for other adverse events associated with systemic chemotherapy. The chemotherapy schedule was delayed, and bleomycin (third course, day 15) was skipped due to adverse effects. After 3 cycles of BEP, the retroperitoneal lymph node metastasis shrunk from 3.0 to 1.5 cm in diameter. In contrast to the good radiological response, the serum AFP level gradually increased during the treatment to 102.6 ng/ml. Therefore, we did not consider the AFP elevation to have derived from residual cancer, and decided to perform close follow-up. During the 3-year follow-up, AFP decreased to around 20 ng/ml, and PET-CT did not show any uptake in the retroperitoneal mass or other sites.

A 79-year-old woman underwent radical cystectomy after neoadjuvant chemotherapy for urothelial carcinoma of bladder (high grade, pT3aN0M0). Six months later, a computed tomography scan revealed multiple lung metastases. Salvage treatment with chemotherapy and pembrolizumab was administered, and a complete response was achieved. Two years after surgery, however, a left adrenal mass appeared, and positron emission tomography／computed tomography showed significant solitary uptake in the left adrenal gland. She underwent left adrenalectomy and histological findings revealed that the adrenal tumor was a metastatic urothelial carcinoma. No new lesion was observed over one year after surgery. Surgical resection should be considered in cases with solitary metastasis who responded systemic treatment.

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.

Spontaneous rupture of renal cell carcinoma (RCC) occurs in 0.3-0.6% of all RCC cases. A 57-yearold woman presented to the emergency department with a chief complaint of hematuria and lower back pein. Ruptures of a kidney tumor and a kidney capsular hematoma were detected using computed tomography. The patient underwent radical right nephrectomy 22 days post admission, and the pathological diagnosis was chromophobe RCC (ChRCC). To our knowledge, this is the third reported case of ChRCC. The previous two cases did not exhibit postoperative recurrence, and yielded good prognoses. However, in our case, liver metastasis occurred 1 month postoperatively, and the prognosis was poor.

The patient was a 21-year-old man with a shadow on a chest roentgenogram taken during a medical checkup. According to blood testing, thoracoabdominal computed tomography, head magnetic resonance imaging, and lung tumor biopsy, we diagnosed a primary retroperitoneal germ cell tumor with multiple lung and brain metastases. Induction chemotherapy (4 courses of Bleomycin, Etoposide and Cisplatin) was started immediately. Because tumor markers remained elevated, salvage chemotherapy (4 courses of paclitaxel, ifosfamide cisplatin) was administered. Since the tumor markers remained elevated third-line chemotherapy was considered. However, because the tumor markers continued to decrease gradually and the tumor continued to shrink on imaging, expectant management was given. Three months later, the tumor markers turned negative, and retroperitoneal lymph node dissection and resection of lung metastases were performed. No cancer cells were found in any of the tissue samples. Careful monitoring after completion of chemotherapy may spare unnecessary chemotherapy.

We examined the efficacy and adverse effects of low-dose intravesical Bacillus Calmette-Guérin (BCG) therapy in patients with non-muscle-invasive bladder cancer. Patients who underwent intravesical BCG therapy (n＝176 ; 198 courses) at our hospital between April 2012 and December 2022 were enrolled. After assigning patients to either the low-dose or regular-dose (40 or 80 mg of BCG Tokyo 172 strain) groups, treatment efficacy and incidence of adverse events were compared. The mean number of BCG infusions in the low-dose and regular-dose groups was 6. 8 and 7. 8,respectively,although the difference was not statistically significant (P＝0.28). The median number of BCG infusions in both groups was eight, with no significant difference between them (P＝0.28). The median follow-up period after BCG therapy was 32 and 37 months in the low-dose and regular-dose groups, respectively. There were no significant differences in recurrence-free or cancer-specific survival between the groups. Although the incidence of adverse events in the low-dose group was lower than that in the regular-dose group, there was no significant differences between the groups. Multivariate analysis showed that fever and reactive arthritis were independent predictors of discontinuation of BCG therapy. Therefore, low-dose BCG therapy may be an effective treatment option for non-muscle-invasive bladder cancer.

A 26-year-old male presented to a hospital with complaints of hemoptysis and right scrotal swelling. Computed tomography (CT) revealed right testicular swelling, multiple lung metastases, and small intestinal wall thickening. The patient's β-human chorionic gonadotropin, alpha-fetoprotein, lactate dehydrogenase, and hemoglobin levels were 103.3 ng/ml, 20.8 ng/ml, 300 U/l, and 11.3 g/dl, respectively. He underwent high orchidectomy after being diagnosed with a testicular tumor and multiple lung metastases. Histopathological examination revealed a mixed germ cell tumor (60% choriocarcinoma, 20% seminoma, 10% embryonal carcinoma, 10% mature teratoma, and 1% yolk sac tumor). As the patient exhibited active gastrointestinal hemorrhage requiring frequent blood transfusions, gastrointestinal endoscopy was performed to investigate its cause. When upper and lower gastrointestinal endoscopies revealed no bleeding, the patient was referred to our hospital for further examination and treatment. A small bowel endoscopy revealed a hemorrhagic jejunal mass. Because endoscopic hemostasis was challenging, we partially resected the small intestine. Pathological findings in the resected lesion were consistent with small intestinal metastasis of the testicular tumor. The tumor markers turned negative after four cycles of BEP and four cycles of TIP chemotherapy. He then underwent resection of the remaining lung tumor, and no residual tumor or recurrence was detected one year later.

We retrospectively analyzed the regions and perioperative outcomes associated with lymph node dissection in patients with prostate cancer. Of 543 patients who underwent robot-assisted radical prostatectomy for prostate cancer with or without lymph node dissection according to the modified D'Amico criteria, 333 (61.3%), 128 (23.6%), and 82 (15.1%) were classified into the non-dissection, limited dissection, and extended dissection groups, respectively. Lymph node metastasis was identified in eight patients : one in the limited dissection group and seven in the extended dissection group. Notably, all eight biopsies showed Gleason scores of 4＋4 or higher, and the initial prostate-specific antigen (PSA) concentration was ≥10 ng/ml in seven of these patients. Lymph node metastasis was detected in areas other than the obturator lymph nodes in five patients (62.5%). Although there was no significant difference in the rate of Clavien- Dindo grade ≥II complications among the three groups, six patients (7.3%) in the extended dissection group developed infectious lymphoceles. In the extended dissection group, the PSA progression-free survival (PSA-PFS) was significantly shorter in patients with than in those without lymph node metastasis (p＜0.001). Because lymph node metastases were rare in the limited dissection group in our cohort of patients with a high risk of localized prostate cancer, achieving a diagnosis seems difficult with limited dissection. By contrast, in the extended dissection group, the PSA-PFS prognosis was significantly worse in lymph node-positive cases. Therefore, considering the high complication risk of lymphoceles, extended dissection should be performed in patients with a high likelihood of lymph node metastasis.