A case of testicular tumor and respiratory failure caused by choriocarcinoma syndrome managed through modified chemotherapy and extracorporeal membrane oxygenation.

Introduction: Choriocarcinoma syndrome with multiple lung metastases has a poor prognosis and causes respiratory failure due to alveolar hemorrhage. We encountered a case where the introduction of extracorporeal membrane oxygenation effectively sustained oxygenation until chemotherapy took effect on lung metastases of testicular tumors. Case presentation: A 35-year-old man with dyspnea was referred to our hospital. He showed left testicular tumor with multiple lung metastases. Serum human chorionic gonadotropin level was also elevated. Reduced chemotherapy was initiated and extracorporeal membrane oxygenation was administered because of low oxygen levels on the fourth day. Chemotherapy successfully reduced the size of the lung masses, and extracorporeal membrane oxygenation was discontinued. Respiratory status improved substantially, but the patient died of brain metastases 4 months later. Conclusion: Extracorporeal membrane oxygenation may be a useful option for managing respiratory failure resulting from choriocarcinoma syndrome until the respiratory condition is improved by chemotherapy for testicular tumors.

Prostate-specific antigen follow-up and management for patients undergoing holmium laser enucleation of the prostate.

OBJECTIVES: To investigate who needs a careful postoperative monitoring for prostate cancer (PCa) after holmium laser enucleation of the prostate (HoLEP). We examined characteristics and oncological outcomes of HoLEP-related PCa. METHODS: Patients who underwent HoLEP during 2002-2017 in a Japanese tertiary center were retrospectively analyzed. Patients were divided into non-PCa, PCa with HoLEP specimen (PCa-Ope), and PCa diagnosed during follow-up (PCa-Post). Outcomes of all HoLEP-related PCa were monitored. RESULTS: Of the total 758, 60 (7.9%) were diagnosed with PCa from resected specimen of HoLEP and 9 (1.2%) were diagnosed postoperatively. Preoperative prostate-specific antigen (iPSA), postoperative PSA (pPSA), and PSA density were significantly higher in both PCa groups than those in non-PCa group. While iPSA significantly correlated to prostate volume (PV), pPSA was not associated with PV. A receiver-operating-characteristics curve demonstrated that pPSA 1.2 ng/mL achieved the optimal cut-off (AUC 0.95) for the incidence of PCa-Post. In addition to the incidence of PCa and iPSA, lower enucleation efficiency (enucleated volume /PV) was significantly associated with pPSA >1.2 ng/mL. Among PCa-Ope, 51 were Grade Group (GG) ≤2 and 42 were followed-up with active surveillance, whereas 8 of 9 PCa-Post were GG ≥3 and 2 progressed to death. CONCLUSIONS: Patients undergoing HoLEP are associated with some risk of potential PCa. While oncological outcomes were favorable among PCa-Ope, postoperative PSA should be carefully monitored even if not diagnosed with PCa with HoLEP specimen. Enucleation efficiency should be also considered not to misread pPSA value.

Contemplation of the Effect of Nivolumab Plus Cabosantinib Therapy on Cerebral Hemorrhage in Patients with Brain Metastasis of Renal Cell Carcinoma: A Case Report.

Although the response to combination therapy has been reported in patients with brain metastases from advanced renal cancer, treatment-related cerebral hemorrhage has not been adequately studied. The CheckMate 9ER clinical trial of nivolumab and cabozantinib excluded patients with brain metastases. Therefore, the associated treatment outcomes in these patients with brain metastases are unclear. Herein, we report a case of bleeding from brain metastases in a patient with advanced renal cancer after gamma knife combination therapy with nivolumab and cabozantinib. Fortunately, the cerebral hemorrhage of the patient was alleviated by conservative treatment. Despite treatment interruption, the metastatic lesions reduced in size, and treatment was gradually resumed. In this case study, we report the risk of cerebral hemorrhage in combination therapy for brain metastasis cases, how to manage hemorrhage cases, and their prognosis.

Impact of Adrenalectomy on Diastolic Cardiac Dysfunction in Patients with Primary Aldosteronism.

Poor prognostic cardiac function is known among some patients with primary aldosteronism (PA). However, studies with echocardiograms on whether the normalization of aldosterone after laparoscopic adrenalectomy (LADX) improves myocardial hypertrophy and diastolic cardiac dysfunction have been inadequate. Between August 2009 and December 2021, 147 patients with unilateral PA who underwent pre- and post-LADX echocardiography at a single center were enrolled in this retrospective study. We evaluated the cardiac impact of LADX by comparing patients who demonstrated complete clinical success (CS) with those who demonstrated partial or absent CS. Adjusted odds ratios (ORs) for not obtaining complete CS were calculated using binomial logistic regression analysis for clinically significant items among the pre- and postoperative clinical and echocardiographic markers. Overall, 47 (29%) and 104 (71%) patients had complete and partial or absent CS, respectively. Compared to patients with complete CS, patients with partial CS or without CS tended to have preoperative low early to late diastolic transmitral flow velocity (E/A) (< 0.8 cm/s) (41% vs. 21%, P < 0.05) and postoperative supranormal left ventricular ejection fraction (LVEF) (> 70%) (37% vs. 21%, P < 0.05). Furthermore, laparoscopic adrenalectomy improved the low and high echocardiographic values of E/A and LVEF, respectively, in both groups. The risk factors for not reaching complete CS were male sex (OR 3.42), low preoperative E/A (OR 3.11), and postoperative supranormal LVEF (OR 3.17). Although low preoperative E/A and postoperative supranormal LVEF are associated with poor clinical outcomes, LADX can improve diastolic cardiac function in patients with PA.

BRAF and MEK Inhibitor Treatment for Metastatic Undifferentiated Sarcoma of the Spermatic Cord with BRAF V600E Mutation.

An 18-year-old Japanese man was diagnosed with an undifferentiated sarcoma of the spermatic cord, with multiple distant metastases to the lungs and bones. The patient received doxorubicin-based standard chemotherapy. Although the chemotherapy was effective, it induced severe adverse events, which led to treatment discontinuation. A comprehensive genomic profiling test using resected tumor tissue revealed the BRAF V600E mutation. Based on the result, the patient received combination therapy with dabrafenib and trametinib. The combination therapy achieved a good response with few adverse events. However, 6.5 months later, pleural metastases and meningeal dissemination had emerged. A liquid comprehensive genomic profiling test was performed after the progression to identify the resistance mechanism, which resulted in the detection of no actionable gene alterations other than BRAF V600E. This report shows that the BRAF V600E mutation may be a promising therapeutic target and that resistance to the targeted therapy could also occur in soft tissue sarcoma. The significance of BRAF mutations across different types of cancer should be validated, and it is necessary to apply targeted therapies and develop methods to overcome resistance based on the optimal use of comprehensive genomic profiling tests.

Severe Inflammatory Idiopathic Multicentric Castleman's Disease Coexisting with Advanced Renal Cancer: A Case Report.

The present case study was conducted on a 74-year-old man who visited our department due to a left renal and retroperitoneal tumor on computed tomography (CT). The patient was diagnosed with left renal cancer lymph node metastasis and was hospitalized a few weeks prior to surgery due to fever, malaise, and severe appetite loss. Biochemical laboratory findings at admission showed markedly high levels of inflammation. The cause of high inflammatory response was paraneoplastic syndrome. Tumor resection was considered necessary, and left nephrectomy and lymphadenectomy were performed; however, it did not improve the inflammatory response. After operation, positron emission tomography-CT revealed hyperaccumulation of 18F-fluorodeoxyglucose in the bone marrow throughout the body. Pathological examination of the resected specimen and bone marrow aspiration revealed the coexistence of idiopathic multicentric Castleman disease (CD) and renal cancer. Prednisolone and tocilizumab were administered for idiopathic multicentric CD and a tyrosine kinase inhibitor for renal cancer; however, they had poor therapeutic effect, and the patient died. CD is characterized by systemic symptoms due to the overproduction of interleukin-6. Treatment for idiopathic multicentric CD involves steroid and anti-interleukin-6 therapy. The diagnostic criteria for CD require the exclusion of malignant tumors although there are some cases in which CD and malignant tumors coexist. The prognosis for CD is relatively good; however, as in this case, the prognosis of CD coexisting with uncontrollable renal cancer is insufficient due to poor improvement in the inflammatory response.

Deliberation on Deferred Cytoreductive Nephrectomy and Postoperative Treatment for Advanced Renal Cell Carcinoma: A Case Report.

In a rare case, free from systemic therapy, deferred cytoreductive nephrectomy was implemented in treating an advanced renal cell carcinoma with liver, lung, and splenic colon metastases. A 59-year-old man diagnosed with advanced renal cell carcinoma underwent deferred cytoreductive nephrectomy due to a partial response to systemic treatment after a period of 1 year. After the surgery, no additional treatment was implemented. Furthermore, after 10 months, the patient had no recurrence of renal cell carcinoma. Through a review of this case and deferred cases in the current literature, we could emphasize the importance of image evaluation and pathological findings as an indication for surgery and subsequent treatment options. However, there is room for debate with regards to the indications for deferred cytoreductive nephrectomy as well as a therapeutic strategy after the surgery. This report discusses the significance of deferred cytoreductive nephrectomy in terms of prognosis and quality-of-life improvement in advanced renal cancer.

Combination Therapy of Pembrolizumab plus Axitinib for a Patient on Hemodialysis with Metastatic Renal Cell Carcinoma: A Case Report.

Here, we discuss the safety and management of adverse events associated with pembrolizumab plus axitinib combination therapy for metastatic renal cell carcinoma in patients on hemodialysis. A 76-year-old man was diagnosed with cT3aN0M0 renal cell carcinoma due to gross hematuria. Stereoscopic radiotherapy for metastatic lesions of the ipsilateral kidney was performed 9 years after right laparoscopic radical nephrectomy. Soon after, the patient started to receive hemodialysis due to end-stage renal disease. Further stereoscopic radiotherapy was needed for metastasis of the ipsilateral kidney and lung. Fifteen years after diagnosis, systemic therapy was necessary to control new metastases, such as in the right scapular bone. We selected pembrolizumab plus axitinib combination therapy as the first-line systemic therapy for any risk as defined by the International Metastatic RCC Database Consortium. Although we needed to pay attention to the adverse events unique to hemodialysis, he underwent this combination therapy without any difficulty for 6 months. Here, we report the practice of combination therapy in patients on hemodialysis in light of the literature.

Clinical Impact of Detecting Low-Frequency Variants in Cell-Free DNA on Treatment of Castration-Resistant Prostate Cancer.

PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.

Impact of cancer therapy on post-treatment ejaculation disorder and sexual life in testicular cancer survivors.

OBJECTIVE: To evaluate the impact of cancer therapy on post-treatment ejaculation in patients with testicular cancer. METHODS: A total of 74 testicular cancer survivors provided completed International Index of Erectile Function-15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." RESULTS: Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post-treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function-15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P < 0.001). CONCLUSION: Ejaculation disorders occur at high rate after retroperitoneal lymph node dissection. Many testicular cancer survivors reporting no sexual intercourse have ejaculation disorders, suggesting an adverse impact on sexual life. Urologists should provide proper counselling regarding the risk of ejaculation disorder and its possible impact on sexual life.

Two cases of anaphylaxis due to contrast media during administration of nivolumab and ipilimumab in metastatic renal cell carcinoma.

A combination therapy of nivolumab and ipilimumab is effective for advanced renal cell carcinoma, but there are concerns about immune-related adverse events. A 46-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On days 16 and 49, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. A 70-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On day 44, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. Both patients were diagnosed with anaphylaxis due to the contrast agent.

Case of atypical femoral fractures that mimicked the typical imaging findings of prostate cancer-induced bone metastasis.

INTRODUCTION: Atypical femoral fractures are atraumatic or minimally traumatic fractures and rare side effects of bone resorption inhibitors. Bone resorption inhibitors are frequently used in the treatment of prostate cancer. CASE PRESENTATION: A 62-year-old man complained of difficulty in walking and left lower limb pain. Androgen deprivation and denosumab therapy for prostate cancer-induced bone metastasis was initiated 27 months ago. Even though the prostate-specific antigen level did not increase, imaging studies indicated the possibility of bone metastasis. The patient underwent bone biopsy; however, no malignancy was detected. Afterward, he had a fall, causing a complete fracture in his left femur. CONCLUSION: Atypical femoral fractures occasionally mimic typical imaging findings and outcomes of bone metastasis. This case is important for recognizing such cases.

Long non-coding RNA HOTAIR promotes cell migration by upregulating insulin growth factor-binding protein 2 in renal cell carcinoma.

Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression. HOTAIR expression in tumors was significantly correlated with nuclear grade, lymph-node metastasis, and lung metastasis. High HOTAIR expression was associated with a poor prognosis in both our dataset and The Cancer Genome Atlas dataset. Migratory capacity was enhanced in RCC cell lines in a HOTAIR-dependent manner. HOTAIR overexpression accelerated tumorigenicity and lung metastasis in immunodeficient mice. Microarray analysis revealed that IGFBP2 expression was upregulated in HOTAIR-overexpressing cells compared with control cells. The enhanced migration activity of HOTAIR-overexpressing cells was attenuated by IGFBP2 knockdown. IGFBP2 and HOTAIR were co-expressed in clinical RCC samples. Our findings suggest that the HOTAIR-IGFBP2 axis plays critical roles in RCC metastasis and may serve as a novel therapeutic target for advanced RCC.

Pure Stage I Seminoma with an Elevated hCG of 25,265 mIU/ml: A Case Report.

We report a histologically pure stage 1 seminoma with an elevated human chorionic gonadotropin (hCG). A 38 year-old man was referred for the evaluation of the left testicular swelling. He showed an elevated serum hCG level of 25,265 mIU/ml with normal a fetoprotein and lactate dehydrogenase. Imaging showed heterogeneous tumor without any metastatic lesions. We conducted 4 courses of chemotherapy before detecting hCG nadir. The final pathological report showed pure seminoma with syncytiotrophoblastic cells but no choriocarcinoma components. The patient remains disease free until present time. The case raised several questions regarding diagnosis and treatment strategy for bulky testicular seminoma.

[Paraganglioma of the bladder : two case reports].

Case 1. A 48-year-old man with no history of hypertension was referred to our hospital with a 1 cm bladder tumor. According to cystoscopy, magnetic resonance imaging and 131I-MIBG scintigraphy, we diagnosed it as a paraganglioma of the bladder. Partial cystectomy was performed. The histological findings supported the diagnosis of paraganglioma of the bladder. Six years later, he was free of any evidence of recurrence. Case 2. A 64-year-old woman with hypertension was pointed out to have a 1cm bladder mass by ultrasound in a health examination. She was referred to our hospital for further examination. Cystoscopoy revealed a 1 cm intramural nodule covered by intact urothelium at the right posterior wall. Submucosal bladder tumor was not diagnosed as paraganglioma by cold punch biopsy. So, transurethral resection of the bladder tumor was performed for differential diagnosis. The tumor was hypervascular and involved the muscular layer of the bladder. Although a transient elevation of blood pressure occurred during the procedure, the tumor was resected as completely as possible. The histological diagnosis was paraganglioma of the bladder. She has been followed up for 27 months after operation without any evidence of recurrence.

A case of renal cell carcinoma with inferior vena cava tumor thrombus diagnosed during pregnancy.

Renal cell carcinoma (RCC) during pregnancy is rare, and the treatment of this condition requires appropriate steps to treat both the patient and the fetus. To the best of our knowledge, this is the first report to describe a case of RCC with tumor thrombus in the inferior vena cava (IVC) occurring during pregnancy. The affected 46-year-old pregnant woman with placenta previa was clinically diagnosed with cT3bN0M0 RCC at 25 weeks gestation. Therapeutic considerations included risk of sudden pulmonary embolism, risk of thrombosis or intraoperative hemorrhage, and safe delivery of the fetus. After extensive consultation with obstetricians and pediatricians, the surgical management was divided into two steps. First, the patient underwent Caesarean section and simultaneous hysterectomy at 26 weeks gestation. Then, 16 days after delivery, when hemodynamics and hemostasis had improved due to termination of gestation, the patient underwent radical nephrectomy with concomitant IVC thrombectomy.

[Effectiveness of DMSO intravesical therapy for lower urinary symptoms of primary amyloidosis localized in the urinary bladder : a case report].

Primary amyloidosis localized in the urinary bladder is comparatively rare,and 40% of the patients complain of lower urinary tract symptoms (LUTS). Although standard management for amyloidosis localized in the urinary bladder is not established,transurethral resection (TUR) is performed in most of the cases to diagnose the disease and to control bleeding. TUR is not considered as radical therapy for amyloidosis localized in the urinary bladder because of frequent recurrence. Dimethyl sulfoxide (DMSO) administered through intravenous,percutaneous or intravesical route has been shown to be effective for treating and preventing recurrence of the disease,but its effect on LUTS due to amyloidosis localized in the urinary bladder has not been demonstrated. We report a case showing improvement of LUTS and in which recurrence of amyloidosis localized in the urinary bladder was prevented for 18 months by intravesical DMSO therapy.

[Annular rectal constriction caused by infiltrating bladder carcinoma: a case report].

A 64-year-old man was referred to our hospital with chief complaints of gross hematuria and pollakisuria. Cystoscopic examination showed non-papillary broad basis tumor on the left lateral wall involving the left ureteral orifice. Computed tomography (CT) and magnetic resonance imaging revealed left hydronephrosis and urinary bladder tumor which extended outside of the bladder wall. Transurethral biopsy showed grade 3 urothelial carcinoma with glandular differentiation including signet ring cells. Radical cystectomy, left nephrureterectomy and right ureterocutaneostomy were performed. Pathological examination showed urothelial carcinoma; pT3aN0. Lymph node metastasis occurred five months later. Three courses of M-VAC chemotherapy (methotrexate, vinblastine, adriamycin, cisplatin) were done with little effectiveness. Sixteen months after the operation, he complained of anorexia and tenesmus, and CT showed annular thickening of the rectal wall. A fecal diversion was performed, but he died two months later.