Pembrolizumab Therapy Leading to Complete Remission for Recurrence of Pulmonary Metastases after their Resection and Radical Cystectomy following Gemcitabine and Cisplatin Therapy.

A 64-year-old man was diagnosed with invasive bladder and right lower ureteral urothelial cancer with right pelvic lymph node and lung metastases. He received four courses of gemcitabine and cisplatin therapy. He underwent lung metastasectomy and radical cystoprostatectomy, with not only primary lesions but also metastatic lesions showing a complete response. New multiple lung metastases were revealed five months after adjuvant chemotherapy. On starting pembrolizumab therapy, the metastatic lesions are notably reduced in size. He is currently receiving pembrolizumab therapy, and no recurrence has been observed for over one year.

Risk of transfusion-transmitted infection with severe acute respiratory syndrome coronavirus 2 from blood donors in Japan.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) essentially affects respiratory organs and tissues. SARS-CoV-2 RNAemia is often associated with more severe cases of coronavirus disease 2019 (COVID-19) compared to cases without RNAemia. To determine the impact of the pandemic on transfusion medicine, particularly transfusion-related infection, we examined the frequency of blood donation with RNAemia, the viral RNA (vRNA) concentration, and any possibility of transfusion-transmitted infection (TTI) among transfusion recipients. STUDY DESIGN AND METHODS: vRNA was examined in plasma/serum samples from 496 of 513 blood donors who reported having been infected with SARS-CoV-2 within 2 weeks of donation among a total of ca. 9.9 million blood donations in Japan between January 15, 2020, and December 31, 2021. The clinical course of patients transfused with the blood component containing vRNA was also examined. RESULTS: vRNA was detected in 23 of 496 samples. The median period from blood donation to COVID-19 onset was 1 day in 16 RNAemia-positive donors. Most samples had vRNA concentrations below the limit of quantification. Three patients were transfused with either a packed red blood cell or platelet concentrate that tested positive for vRNA, showing no COVID-19 symptoms and testing negative for vRNA in post-transfusion blood. CONCLUSION: The rate of RNAemia was 4.6% among blood donors who were found to be infected with SARS-CoV-2 shortly after donation, and vRNA concentrations in their donated blood were extremely low. There was no evidence of TTI in the recipients transfused with RNAemia-positive blood components. TTI risk in SARS-CoV-2 is negligible.

A case of cabozantinib therapy leading to complete remission for massive intra-intestinal bleeding and worsening metastatic sites following nivolumab and ipilimumab therapy.

A woman in her 50s had recurrent renal cell carcinoma six years after nephrectomy. The patient was treated with nivolumab plus ipilimumab therapy starting in May 2022. She was rushed to hospital due to melena and severe anemia in September 2022. CT showed massive leakage of contrast medium into the gastrointestinal tract and mild enlargement of the metastatic tumors. Nivolumab was discontinued and she was started on cabozantinib as second-line therapy. After cabozantinib therapy, the anemia subsided. The metastatic tumors have shrunk significantly, with no further recurrence being observed as of September 2023.

Complete remission following pembrolizumab therapy for a patient with nephroureterectomy positive-margin carcinoma in situ and bladder cancer unresponsive to Bacille Calmette-Guérin therapy.

An 82-year-old man was diagnosed with synchronous non-muscle-invasive bladder cancer and left lower ureteral carcinoma. He underwent transurethral resection of the bladder tumor, followed by total left nephroureterectomy after preoperative chemotherapy with four courses of gemcitabine and carboplatin. Histopathological findings showed positive-margin carcinoma in situ. In addition, since recurrence of non-muscle-invasive bladder cancer was observed in the bladder, Bacille Calmette-Guérin intravesical infusion therapy was performed, but the cancer persisted due to treatment resistance. After that, pembrolizumab therapy was performed, and complete remission was achieved.

Oligomeric state of the N-terminal domain of DnaT for replication restart in Escherichia coli.

DNA replication stops when chemical or physical damage occurs to the DNA. Repairing genomic DNA and reloading the replication helicase are crucial steps for restarting DNA replication. The Escherichia coli primosome is a complex of proteins and DNA responsible for reloading the replication helicase DnaB. DnaT, a protein found in the primosome complex, contains two functional domains. The C-terminal domain (89-179) forms an oligomeric complex with single-stranded DNA. Although the N-terminal domain (1-88) forms an oligomer, the specific residues responsible for this oligomeric structure have not yet been identified. In this study, we proposed that the N-terminal domain of DnaT has a dimeric antitoxin structure based on its primary sequence. Based on the proposed model, we confirmed the site of oligomerization in the N-terminal domain of DnaT through site-directed mutagenesis. The molecular masses and thermodynamic stabilities of the site-directed mutants located at the dimer interface, namely Phe42, Tyr43, Leu50, Leu53, and Leu54, were found to be lower than those of the wild-type. Moreover, we observed a decrease in the molecular masses of the V10S and F35S mutants compared to the wild-type DnaT. NMR analysis of the V10S mutant revealed that the secondary structure of the N-terminal domain of DnaT was consistent with the proposed model. Additionally, we have demonstrated that the stability of the oligomer formed by the N-terminal domain of DnaT is crucial for its function. Based on these findings, we propose that the DnaT oligomer plays a role in replication restart in Escherichia coli.

A new workflow of the on-line 1.5-T MR-guided adaptive radiation therapy.

PURPOSE: The aim of this study was to develop a new workflow for 1.5-T magnetic resonance (MR)-guided on-line adaptive radiation therapy (MRgART) and assess its feasibility in achieving dose constraints. MATERIALS AND METHODS: We retrospectively evaluated the clinical data of patients who underwent on-line adaptive radiation therapy using a 1.5-T MR linear accelerator (MR-Linac). The workflow in MRgART was established by reviewing the disease site, number of fractions, and re-planning procedures. Five cases of prostate cancer were selected to evaluate the feasibility of the new workflow with respect to achieving dose constraints. RESULTS: Between December 2021 and September 2022, 50 consecutive patients underwent MRgART using a 1.5-T MR-Linac. Of these, 20 had prostate cancer, 10 had hepatocellular carcinoma, 6 had pancreatic cancer, 5 had lymph node oligo-metastasis, 3 had renal cancer, 3 had bone metastasis, 2 had liver metastasis from colon cancer, and 1 had a mediastinal tumor. Among a total of 247 fractions, 235 (95%) were adapt-to-shape (ATS)-based re-planning. The median ATS re-planning time in all 50 cases was 17 min. In the feasibility study, all dose constraint sets were met in all 5 patients by ATS re-planning. Conversely, a total of 14 dose constraints in 5 patients could not be achieved by virtual plan without using adaptive re-planning. These dose constraints included the minimum dose received by the highest irradiated volume of 1 cc in the planning target volume and the maximum dose of the rectal/bladder wall. CONCLUSION: A new workflow of 1.5-T MRgART was established and found to be feasible. Our evaluation of the dose constraint achievement demonstrated the effectiveness of the workflow.

Prostate-specific antigen doubling time following radium-223 treatment as a predictor of the clinical course in patients with metastatic castration-resistant prostate cancer.

Objectives: To identify useful biomarkers by reviewing laboratory data for a predictor of the clinical course following treatment with radium-223 dichloride (Ra-223) in patients with metastatic castration-resistant prostate cancer. Methods: Eighteen metastatic castration-resistant prostate cancer patients who were administered Ra-223 at our hospital were retrospectively enrolled in this study. Prostate-specific antigen doubling times before and after the administration of Ra-223 were evaluated as prognostic factors for metastatic castration-resistant prostate cancer patients treated with Ra-223 using the Kaplan-Meier method and Log-rank test. Results: Four patients failed to complete the planned six-time Ra-223 treatments with the exacerbation of their condition. In the 14 patients who completed the planned Ra-223 treatment, before the Ra-223 treatment, no significant differences were observed in overall survival between patients with prostate-specific antigen doubling time of 6 months or less and those with prostate-specific antigen doubling time of more than 6 months or stable (p = 0.642). Following the completion of the Ra-223 treatment, overall survival was significantly shorter in patients with prostate-specific antigen doubling time of 6 months or less than in those with prostate-specific antigen doubling time of more than 6 months or stable (p = 0.007). Conclusion: Prostate-specific antigen doubling time after the Ra-223 treatment is a useful predictor of the clinical course following treatment in metastatic castration-resistant prostate cancer patients.

Primary lung cancer treatable with radical resection after complete remission with pembrolizumab therapy following gemcitabine and carboplatin chemotherapy for multiple metastases of bladder cancer.

Introduction: We report a patient with the complete remission of multiple metastases and primary bladder lesions of bladder cancer who developed primary lung cancer requiring radical resection. Case presentation: A 68-year-old man diagnosed with invasive bladder cancer, right hydroureteronephrosis, and multiple metastases were administered six courses of gemcitabine and carboplatin chemotherapy and thereafter has been receiving pembrolizumab therapy. Bladder cancer and multiple metastases decreased in size, whereas a ground-glass opacity lesion in the lung gradually increased in size. Fluorodeoxyglucose-positron emission tomography revealed the accumulation of fluorodeoxyglucose in the ground-glass opacity lesion only. The patient was diagnosed with primary lung cancer and underwent a thoracoscopic lobectomy. Histopathological findings showed ALK-negative, EGFR L858R mutation-positive invasive adenocarcinoma with a programmed death-ligand 1 tumor proportion score of less than 1%. Conclusion: This is the first case report of patients with the complete remission of multiple metastases of bladder cancer who developed primary lung cancer requiring radical resection.

Laparoscopic Nephroureterectomy with Heminephrectomy for Urothelial Carcinoma of the Upper Renal Pelvis on the Left Side of the Horseshoe Kidney.

A 70-year-old male was diagnosed with urothelial carcinoma of the upper renal pelvis on the left side of the horseshoe kidney. Preoperative thin-slice contrast-enhanced CT with three-dimensional reconstruction of the images revealed that two arteries arising from the aorta supplied the left moiety of the horseshoe kidney. He underwent laparoscopic transperitoneal nephroureterectomy with heminephrectomy on the left side of the horseshoe kidney visualized by indocyanine green fluorescence system. The histopathological findings of the renal pelvic tumor revealed invasive urothelial carcinoma with squamous differentiation, high grade, and pT3.

Multidisciplinary Therapy in Men with Newly Diagnosed Oligometastatic Prostate Cancer.

PURPOSE: To assess the use of aggressive local therapy with systemic therapy for patients with oligometastatic prostate cancer. PATIENTS AND METHODS: Patients with oligometastatic prostate cancer received systemic therapy centered on androgen deprivation therapy (ADT). After six months or more of ADT, the patients received radiation therapy or surgery for the prostate, and radiation therapy for all metastatic sites. ADT was continued for 2-3 years after local therapy. RESULTS: Twelve patients who were judged to be able to undergo radiotherapy or surgical treatment of the prostate and radiation therapy for all metastatic sites and one case of pubic bone recurrence after radical prostatectomy were included. Bone metastases (n = 11) and para-aortic lymph node metastases (n = 2) were found. The number of bone metastases was one (n = 7), two (n = 3), and three (n = 1). Radiation therapy (70-74 Gy) was performed on the prostate in 11 of 12 patients. A prostatectomy was performed on one patient who was judged to be unable to receive a sufficient dose to the metastatic site when radical radiation was applied to the prostate. Radiation therapy (45-60 Gy) was performed on all metastatic sites. Prostate-specific antigen (PSA) levels increased again during treatment in three patients. There was a significant difference in PSA levels before local therapies between the three patients who developed castration-resistant prostate cancer (CRPC) during the course of treatment and the eight patients who did not progress to CRPC (p = 0.012). There was also a significant difference in PSA levels after local therapies between the three patients who developed CRPC during the course of treatment and the eight patients who did not progress to CRPC (p = 0.012). Four patients completed treatment. In one patient in whom the testosterone level recovered to the normal level the PSA level remained the level below the measurement sensitivity. CONCLUSION: Aggressive local therapy in combination with systemic therapy centered on ADT is a promising treatment option for oligometastatic prostate cancer.

Successful Response of Pembrolizumab Rechallenge after Radiotherapy for a Patient with Bladder Cancer of Nonresponse of Pembrolizumab First Challenge.

We report a patient with advanced bladder cancer in which the primary lesion and metastatic site disappeared following the pembrolizumab therapy rechallenge after radiotherapy for bladder cancer lesion of nonresponse of pembrolizumab first challenge. A 76-year-old man with advanced bladder cancer received three courses of the chemotherapy with gemcitabine and cisplatin combination; however, the chemotherapy was stopped because of adverse events. The patient started pembrolizumab therapy; however, the effect was not observed. Radiation therapy was given to the primary lesion and pelvic lymph node metastases for the purpose of local control of the lesions. Because the primary lesion was regrowth and para-aortic lymph node metastasis appeared, pembrolizumab therapy was resumed. Thereafter, the primary lesion and metastatic site disappeared.

Clear Cell Adenocarcinoma of the Ureter Similar to Clear Cell Renal Cell Carcinoma Histology.

A 70-year-old woman was referred to our hospital with gross hematuria and diagnosed with right invasive ureteral cancer and bladder urothelial carcinoma in situ. Intravesical BCG therapy and neoadjuvant chemotherapy with carboplatin and gemcitabine were performed at the same time. Subsequently, laparoscopic right nephroureterectomy was performed. Urothelial carcinoma in situ persisted; however, most of the tumor was clear cell carcinoma. The clear cell carcinoma lesion had clear cytoplasm with round nuclei and visible nucleoli in an insular arrangement as is the case with clear cell renal cell carcinoma. No transitional lesion between clear cell adenocarcinoma and urothelial carcinoma was presented. The clear cell carcinoma lesion was GATA3 negative and HNF4α positive; however, the urothelial cancer lesion was GATA3 positive and HNF4α negative. Clear cell carcinoma was diagnosed as clear cell adenocarcinoma similar to clear cell renal cell carcinoma histology.

A structural model of the PriB-DnaT complex in Escherichia coli replication restart.

In Escherichia coli, DNA replication is restarted following DNA repair by the PriA-dependent pathway, in which the binding and dissociation of proteins such as PriA, PriB, and DnaT on ssDNA lead to the formation of a protein-DNA complex for recruiting the DnaB-DnaC replication protein complex. However, the structure of the PriB-DnaT complex, which is an essential step in the PriA-dependent pathway, remains elusive. In this study, the importance of His26 in PriB for replication restart was reconfirmed using plasmid complementation. Furthermore, we used NMR to examine the DnaT interaction sites on PriB. We also evaluated the PriB-DnaT peptide complex model, which was prepared by in silico docking, using molecular dynamic simulation. From these data, we propose a structural model that provides insight into the PriB-DnaT interaction.

Urothelial carcinoma with sarcomatoid/osteosarcoma variant of the bladder: A case report.

A 67-year-old man was diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection of the lesions in August 2017. The pathological findings revealed high-grade urothelial carcinoma. The tumor relapsed as urothelial carcinoma with sarcomatoid/osteosarcoma variant with vascular invasion, and transurethral resection was performed in December 2017. He underwent laparoscopic radical cystoprostatectomy and orthotopic neobladder reconstruction using ileum in March 2018. The patient developed lung metastasis in July 2018. He underwent four courses of chemotherapy with doxorubicin and thoracoscopic left lower lobectomy of the lung in October 2018.

Emergence of undifferentiated urothelial carcinoma after pembrolizumab treatment for patient with invasive urothelial bladder cancer: A case report.

An 83-year-old man received pembrolizumab treatment after anticancer chemotherapy with gemcitabine and cisplatin for advanced bladder cancer. Pathological findings revealed invasive urothelial carcinoma with squamous differentiation before treatment. After seven courses of pembrolizumab treatment, the tumor disappeared. After 15 courses of the treatment, the tumor regrew. Pathological findings revealed invasive undifferentiated urothelial carcinoma consisting of relatively small tumor cells of the same size as lymphocytes, negative for neuroendocrine markers. Programmed death-ligand 1 expressions in tumor tissue changed from positive before treatment to negative after pembrolizumab treatment.

Granulocytic/myeloid sarcoma with trisomy 21 presented as an epididymal tumor: A case report and review of the literature.

Myeloid sarcoma is an extramedullary tumor composed of immature myeloid cells and occurs in various extramedullary sites. We report a 48-year-old man diagnosed with myeloid sarcoma in the epididymis. He was admitted to our hospital due to a painless right intrascrotal mass. Magnetic resonance imaging showed a 30 mm tumor in the right epididymis, and we subsequently performed right high orchiectomy. The pathological diagnosis was myeloid sarcoma. Bone marrow aspiration and biopsy revealed no hematological disease, and cytogenetic analysis in the bone marrow showed normal karyotype. He was diagnosed with isolated myeloid sarcoma in the epididymis. Six months after the operation, myeloid sarcoma recurred in the para aorta and left sub-diaphragm. Bone marrow examination revealed myelodysplastic syndrome, and cytogenetic analysis showed 46, XY. We performed surgical resection of the recurrent mass, and cytogenetic analysis showed 47, XY, +21. He was diagnosed with recurrent MS with adult-onset trisomy 21. Although the effect of trisomy 21 on prognosis is unknown, the patient is currently undergoing systemic chemotherapy with maintained remission.

Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer.

A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.

Simultaneous Laparoscopic Surgery for Bladder Diverticulum and Urachal Remnant: A Case Report.

A 44-year-old woman visited a hospital with microscopic hematuria in June 2009. Computed tomography showed a large bladder diverticulum at right lateral wall and urachal remnant. Cystoscopic examination showed a large diverticulum at the right lateral wall that closes to the dome. She was followed up closely without therapeutic intervention; however, the residual urine increased gradually and frequent bladder diverticulitis developed. She underwent laparoscopic bladder diverticulectomy and excision of the urachal remnant simultaneously without any complications in August 2017. Laparoscopic approach for a large bladder diverticulum and urachal remnant is useful with safe, effective, and minimally invasive.

Spontaneous Passage of Left Ureteral Multiple Calculi from Caliceal Diverticular Calculi: A Case Report.

Caliceal diverticular calculi are rather fixed and they are rare to be delivered spontaneously. We experienced a case of spontaneous passage of left ureteral multiple calculi from caliceal diverticular calculi. A 65-year-old female suffered from left back pain and was referred to our hospital. She was found to have left ureteral multiple calculi and left caliceal diverticular calculi. After a month observation, all ureteral calculi were delivered spontaneously. Multiple ureteral calculi from caliceal diverticular calculi could be delivered spontaneously and conservative management may be an option for the treatment.

Unicentric Castleman's disease located between the aorta and inferior vena cava: A case report.

We report a 70-year-old woman diagnosed with unicentric Castleman's disease with a contrast well-enhanced retroperitoneal tumor of 25 mm in diameter that located between the aorta and inferior vena cava. The imaging finding did not suggest any specific features, and no other lesion was detected. Laboratory examinations indicating malignant lymphoma such as soluble interleukin-2 were all negative. We resected the retroperitoneal tumor laparoscopically, and histopathological examination revealed hyaline vascular type Castleman's disease. Although complete resection of hyaline vascular type unicentric Castleman's disease results in a good prognosis, a late relapse has been reported and long-term follow-up is warranted.