Metabolic and Epigenetic Reprogramming in a Case of Nuclear Protein in Testis (NUT) Carcinoma of the Retroperitoneum.

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive carcinoma, driven by genetic rearrangement of the NUT midline carcinoma family member 1 (NUTM1) gene on chromosome 15q14. Recently, a tight link has been suggested between genetic abnormalities and subsequent metabolic and epigenetic dysregulation to drive the progression of malignant tumors. However, it remains elusive whether such reprogramming could contribute to the pathogenesis of NUT carcinoma. We herein report an autopsy case of NUT carcinoma arising in the retroperitoneum of a 31-year-old male. Notably, reprogramming of glycolytic metabolism and epigenetic histone modifications was observed in this unusual NUT carcinoma case, and this phenomenon was further confirmed by an in vitro cell culture model with bromodomain containing 4 (BRD4)-NUT overexpression. The rationale for documenting the case is based on our findings to reveal that metabolic and epigenetic reprogramming could be one of the contributing factors to the pathogenesis of NUT carcinoma, which could be exploitable as a novel therapeutic target for this rare and aggressive cancer type.

5-Aminolevulinic acid-based photodynamic diagnosis for detection of urothelial carcinoma cells in bladder washing sediment suspension: A pilot study.

BACKGROUND: Bladder cancer is a common malignant disease in developed countries. Early detection of malignancy is important using urine cytology. The 5-aminolevulinic acid (ALA)-based photodynamic diagnosis (ALA-PDD) has not been routinely applied in urine cytology analysis yet, although it has been well accepted for tumor lesion marking in cystoscopy. METHODS: A total of eight volunteers were enrolled in this study. The cells of sediment suspension from bladder washing fluid and random urine were stained by ALA-induced protoporphyrin IX (ALA-PpIX) and the fluorescent intensity of ALA-PpIX was analyzed by ImageJ. RESULTS: The cutoff value of fluorescent intensity was 90.260 per pixel. The proposed protocol provided an objective fluorescent intensity for evaluation. Sensitivity was 0.931 and specificity was 1.000. CONCLUSIONS: The staining procedure applied was ALA-PpIX for suspicious cells in the cellular suspension from bladder wash fluid and random urine. ImageJ was applied to the objective measurement for the fluorescent intensity of the stained cells. The cutoff value for the positive result was 90.260 per pixel. Therefore, the protocol proposed in this study provides a potential means to enhance accuracy for urine cytology analysis.

Assessment of Feasibility of Robot-assisted Radical Cystectomy in Patients With Advanced Bladder Cancer Treated With Maintenance Hemodialysis Therapy.

BACKGROUND/AIM: To clarify the perioperative and oncological outcomes of robot-assisted radical cystectomy (RARC) in advanced bladder cancer (BC) patients treated with maintenance hemodialysis (HD) therapy. PATIENTS AND METHODS: We retrospectively evaluated patients receiving HD therapy who had undergone RARC or open radical cystectomy (ORC) for BC between April 1988 and December 2021 at two affiliated institutions. We compared the surgical outcomes and survival after radical cystectomy between patients treated with RARC and those treated with ORC. RESULTS: Thirty-six patients were evaluated, and eight (22%) and 28 (78%) received RARC and ORC, respectively. RARC was more frequently conducted than ORC in elderly patients (median: 75.5 vs. 68.2 years, p<0.05). Regarding postoperative surgical outcomes, the estimated blood loss volume (median: 75 ml vs. 627 ml, p<0.05) was significantly lower in the RARC group than that in the ORC group. A lower blood transfusion rate (25% vs. 67%, p=0.170) was observed. Moreover, there were no differences in operative time (median: 255 vs. 294 min, p=0.232) or complication rate (Clavien-Dindo grade, any grade: 50% vs. 46%, p=0.858; grade 3 or more: 13% vs. 14%, p=0.897). The 11-year overall survival rate did not differ between the two groups (88% vs. 74%, p=0.365). CONCLUSION: The perioperative outcomes of RARC in patients undergoing HD therapy were comparable to those of ORC. RARC is a potentially feasible surgical option even in patients with high comorbidities.

Perioperative outcomes following robot-assisted partial nephrectomy for renal cell carcinoma according to surgeon generation.

OBJECTIVE: The experience of performing robot-assisted partial nephrectomy (RAPN) is associated with better surgical outcomes. However, surgeon's generation may impact surgical outcomes. We evaluated the perioperative outcomes of RAPN between first- and second-generation surgeons according to the surgeon's experience. METHODS: This study included 529 patients who underwent RAPN for renal cell carcinoma from January 2013 to November 2018. Four specific surgeons performed the surgery. According to the surgeon's generation, the patients were divided into two groups: first-generation and second-generation. To reflect the learning curve of RAPN, the surgical outcomes of each case (1-50, 51-100, 101-150) were evaluated between these groups. RESULTS: Between 1 to 50 cases and 101-150 cases, no significant differences in patient characteristics were observed between the two generations. Between 51-100 cases, age at surgery was significantly younger in the first-generation than in the second-generation group (58 years vs. 64 years, p = 0.04). The second-generation group had a shorter operation time in cases 1-50 (169 min vs. 188 min, p = 0.0001), 51-100 (145 min vs. 169 min, p = 0.008), and 101-150 (142 min vs. 165 min, p = 0.009), than the first-generation group. Although shorter WIT and higher trifecta achievement were observed in the second-generation group than in the first-generation group between 1-50 cases, the difference was not noted between 51-100 cases and 101-150 cases. CONCLUSION: Patients operated by second-generation surgeons had better surgical outcomes than first-generation surgeons, especially during the early experience period, which might result from their assistance experience, sophisticated surgical procedures refined by the first-generation, and the first-generation surgeon's introduction.

A case of novel coronavirus disease after combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma.

INTRODUCTION: We present a case of novel coronavirus disease-2019 that underwent combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma. CASE PRESENTATION: A 50-year-old man complained of anorexia and weight loss. Contrast-enhanced computed tomography revealed a solid mass of 57 mm in diameter with cysts in the right kidney, along with liver, lung, and multiple bone metastases. Computed tomography-guided biopsy of the right kidney was performed, and a diagnosis of clear cell renal cell carcinoma was made. Three weeks after nivolumab and ipilimumab administration, the patient contracted coronavirus disease-2019. Anticoagulation therapy (dalteparin) was administered for 4 days once infection was confirmed, after which dexamethasone was administered for 10 days. The patient survived without experiencing worsened respiratory symptoms. CONCLUSION: We administered nivolumab and ipilimumab combination therapy as treatment for metastatic renal cell carcinoma. No side effects or immune-related adverse events were observed for a short time.

Two Laparotomy Surgeries to Achieve Hemostasis After Kidney Transplantation in a Patient With Frailty: A Case Report.

BACKGROUND: The assessment of frailty before and after kidney transplantation is becoming more important in the aging population. It is recommended to recognize the post-transplant risks and establish a treatment strategy. We report the case of a patient who underwent 2 laparotomy hemostasis procedures due to frailty after kidney transplantation. CASE REPORT: A 72-year-old woman presented with end-stage renal failure due to an unknown primary disease. She was also found to be frail when assessed using the physical frailty phenotype. She underwent ABO-incompatible kidney transplantation from her husband at the end of March 2020. On the first postoperative day, re-operation for hematoma evacuation was performed. The bleeding point could not be identified at that time. Progression of anemia was observed on the sixth postoperative day, and computed tomography showed no obvious bleeding. Subsequently, the renal allograft started functioning immediately, without rejection. However, emergency laparotomy for hematoma removal was performed on the 22nd postoperative day. Bleeding had occurred from the anastomotic region of the renal allograft artery and the external iliac artery. Her serum creatinine levels and renal function remained stable one month after surgery. CONCLUSIONS: We encountered a case of living-donor kidney transplantation in a frail older woman who underwent 2 laparotomies due to hemorrhage. Perioperative risk management is necessary for patients with a high risk of postoperative bleeding. To ensure a good outcome, preoperative and postoperative rehabilitation is important for patients with frailty.

Suspected Pneumonia Caused by Coronavirus Disease 2019 After Kidney Transplantation: A Case Report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection may become more severe in those who have undergone kidney transplantation than in the general population. False-negative reverse transcription-polymerase chain reaction (RT-PCR) results have been reported for COVID-19 infection. Patients might carry infection even though RT-PCR results are negative. CASE REPORT: A 65-year-old man with a 19-year history of ABO-incompatible kidney transplantation presented with fever and arthralgia. Although the RT-PCR result was negative, a focal slit-glass shadow in the left upper lobe on computed tomography (CT) suggested COVID-19 pneumonia. His symptoms did not improve until after 10 days, and CT showed multiple slit-glass shadows in the bilateral lung fields. However, RT-PCR remained negative. The patient was admitted, and mycophenolate mofetil was discontinued. Anticoagulants were administered on the third day of hospitalization. Because of poor oxygenation, the patient was intubated in the intensive care unit on the fifth day, and sivelestat sodium was administered. The patient was extubated on the 12th day after improvement in oxygenation. There was no exacerbation, and CT showed improvements on day 51. CONCLUSION: We report a case of pneumonia with suspected COVID-19 infection 18 years after living donor kidney transplantation. If COVID-19 is suspected, infection control and aggressive therapeutic interventions should be undertaken while considering the possibility of a positive result.

Allogeneic Kidney Transplantation After COVID-19: A Case Report.

BACKGROUND: Patients undergoing organ transplantation are immunosuppressed and already at risk of various diseases. We report about a patient who underwent ABO-incompatible kidney transplantation after coronavirus disease 2019 (COVID-19) without a recurrence of infection. CASE REPORT: A 68-year-old woman presented with end-stage renal failure owing to primary autosomal dominant polycystic kidney disease; accordingly, hemodialysis was initiated in September 2020. Her medical history included bilateral osteoarthritis, lumbar spinal stenosis, hypertension, and hyperuricemia. In mid-January 2021, she contracted severe acute respiratory syndrome coronavirus 2 infection from her husband. Both of them were hospitalized and received conservative treatment. Because their symptoms were mild, they were discharged after 10 days. The patient subsequently underwent ABO-incompatible kidney transplantation from her husband who recovered from COVID-19 in March 2021. Before kidney transplantation, her COVID-19 polymerase chain reaction test was negative, confirming the absence of pre-existing COVID-19 immediately before the procedure. Computed tomography revealed no pneumonia. Initial immunosuppression was induced by administering tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, rituximab, and 30 g of intravenous immunoglobulin. Double-filtration plasmapheresis and plasma exchange were performed once before ABO-incompatible kidney transplantation. The renal allograft functioned immediately, and the postoperative course was normal without rejection. COVID-19 did not recur. In addition, her serum creatinine levels and renal function had otherwise remained stable. CONCLUSION: Living kidney transplantation was safely performed in a patient with COVID-19 without postoperative complications or rejection. During the COVID-19 pandemic, the possibility of severe acute respiratory syndrome coronavirus 2 infection during transplantation surgery must be considered.

Fluorescence In Situ Hybridization for the Origin of De Novo Renal Cell Carcinoma in a Kidney Allograft: A Case Report.

BACKGROUND: We present a rare case of de novo renal cell carcinoma that developed in an allograft kidney 14 years after transplantation. CASE REPORT: A 39-year-old man underwent living donor kidney transplantation from his mother. After 14 years, routine screening ultrasonography revealed a solid mass of 30-mm diameter in the kidney allograft. Partial nephrectomy was performed by clamping the renal artery under in situ cooling. Tissue histology revealed clear cell carcinoma with negative surgical margins. We explored the tumor's genetic origin using fluorescence in situ hybridization to analyze the X and Y chromosomes of the tumor cells. Postoperative hemodialysis was avoided, and the patient's serum creatinine level remained stable. CONCLUSIONS: Fluorescence in situ hybridization clearly indicated that the tumor originated from the donor and that the tumor vasculature originated from the recipient. The patient recovered well and remains without any tumor recurrence.

Detection of a peritumoral pseudocapsule in patients with renal cell carcinoma undergoing robot-assisted partial nephrectomy using enhanced MDCT.

To investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.