Retroperitoneal sarcoma: a 10-year follow-up analysis using hospital-based cancer registry data in Japan.

OBJECTIVES: We sought clinical characteristics, survival outcomes, and prognostic factors for overall survival of retroperitoneal sarcoma in Japan. METHODS: A Japanese hospital-based cancer registry database with a pivotal 10-year follow-up was used to identify and enroll patients, registered from 106 institutions, diagnosed with retroperitoneal sarcoma in 2008-2009. Treating hospitals were divided by hospital care volume; high-volume hospitals and low-volume hospitals were defined as ≥ 4 and < 4 cases/year, respectively. RESULTS: A total of 91 men and 97 women were included, with a median age of 64 years. The most common histological type was liposarcoma in 101 patients, followed by leiomyosarcoma in 38 patients. The 5-year and 10-year overall survival rates were 44.1 and 28.3%. The majority of patients (n = 152, 80.9%) were treated at low-volume hospitals. High-volume hospital patients had higher 10-year overall survival rates than low-volume hospital patients (51.2% vs 23.2%, P = 0.026). Multivariate analysis revealed age over 60 years, treatment in low-volume hospitals and chemotherapy were independent predictors of unfavorable survival while treatment with surgery was an independent predictor of favorable survival. CONCLUSIONS: The possibility of surgical removal was suggested to be the most important prognostic factor for retroperitoneal sarcoma. Better survival was shown in patients treated at high-volume hospitals in our series.

Adult genitourinary sarcoma: analysis using hospital-based cancer registry data in Japan.

BACKGROUND: Genitourinary sarcomas are rare in adults and few large-scale studies on adult genitourinary sarcoma are reported. We aimed to elucidate the clinical characteristics, survival outcomes, and prognostic factors for overall survival of adult genitourinary sarcoma in Japan. METHODS: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with genitourinary sarcoma in 2013. The datasets were registered from 121 institutions. RESULTS: A total of 116 men and 39 women were included, with a median age of 66 years. The most common primary site was the kidney in 47 patients, followed by the paratestis in 36 patients. The most common histological type was liposarcoma in 54 patients, followed by leiomyosarcoma in 25 patients. The 5-year overall survival rates were 57.6%. On univariate analysis, male gender, paratestis as primary organ, and histological subtype of liposarcoma were predictive of favorable survival while primary kidney, bladder, or prostate gland location were predictive of unfavorable survival. On multivariate analysis, primary paratestis was an independent predictor of favorable survival while primary kidney, bladder, or prostate gland were independent predictors of unfavorable survival. CONCLUSIONS: This is the first report showing the clinical characteristics and survival outcomes of adult genitourinary sarcoma in Japan using a real-world large cohort database.

Plasma circulating tumor DNA profiling in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Molecular analysis of tumor tissues has been extensively analyzed in germ cell tumors. However, genetic analysis of plasma circulating tumor DNA has been limited. Our objective was to analyze genetic alterations in circulating tumor DNA as well as its impact on prognosis in patients with chemo-refractory germ cell tumors. METHODS: We included 13 patients with chemo-refractory germ cell tumors who relapsed after second-line or higher previous chemotherapy and performed targeted sequencing of plasma cell-free DNA using an AVENIO Expanded kit. RESULTS: Tumor-specific genetic alterations were identified in all patients. The most frequently mutated gene was TP53 (53.4%), followed by PTEN (23.1%), GNAS (15.4%) and MTOR (15.4%). Moreover, EGFR amplification (38.5%) and MET amplification (15.4%) were also identified. We defined two or more single nucleotide variants detected in plasma cell-free DNA as circulating tumor DNA-positive. Kaplan-Meier analysis revealed that overall survival was significantly shorter in circulating tumor DNA-positive patients than circulating tumor DNA negative-patients (median overall survival 3.13 vs. 8.73 months; p = 0.042). CONCLUSION: Analysis of plasma circulating tumor DNA could detect genetic alterations in patients with chemo-refractory GCT. Moreover, detectable circulating tumor DNA in plasma was associated with poor prognosis in those patients. These results suggest that liquid biopsy using analysis of plasma circulating tumor DNA may be clinically useful for germ cell tumor patients.

Clinicopathological features of adrenal malignancies: Analysis of hospital-based cancer registry data in Japan.

OBJECTIVE: To identify the clinicopathological features of adrenal malignancies and analyze the prognoses of patients with adrenal cortical carcinoma (ACC) and malignant pheochromocytoma (MPCC). PATIENTS AND METHODS: We used a hospital-based cancer registry data in Japan to extract cases of adrenal malignancies that were histologically confirmed, diagnosed, and initially treated from 2012-2015. For survival analysis, we used data from the 2008-2009 cohort to estimate 5-year overall survival (OS) by the Kaplan-Meier method. RESULTS: A total of 989 adrenal malignancies were identified in the 2012-2015 cohort. The most common histologies were ACC (26.4%), diffuse large B-cell lymphoma (DLBCL; 25.4%), neuroblastoma (22.2%), and MPCC (11.9%). While most ACC and MPCC patients were in their 60s, DLBCL patients accounted for 61.5% of adrenal malignancies in the over-70 cohort. Among ACC patients with clinical staging data, 46.3% of patients were stage IV. Although surgery was a chief strategy for all stages, younger patients tended to receive combination therapy, including surgery and chemotherapy or hormone therapy. In the 2008-2009 cohort, the 5-year OS rates of ACC (n = 49) and MPCC (n = 23) patients were 56.2% and 86.4% while ACC patients without surgery had 1- and 2-year OS rates of 25.0% and 12.5%. CONCLUSION: In Japan, DLBCL accounted for the majority of adrenal malignancies in older patients. Despite advanced staging, ACC patients were mainly treated with surgery and their prognosis was not satisfactory. Such epidemiological data may be useful in considering initial management strategies.

ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma.

Renal cell carcinoma (RCC) features altered lipid metabolism and accumulated polyunsaturated fatty acids (PUFAs). Elongation of very long-chain fatty acid (ELOVL) family enzymes catalyze fatty acid elongation, and ELOVL5 is indispensable for PUFAs elongation, but its role in RCC progression remains unclear. Here, we show that higher levels of ELOVL5 correlate with poor RCC clinical prognosis. Liquid chromatography/electrospray ionization-tandem mass spectrometry analysis showed decreases in ELOVL5 end products (arachidonic acid and eicosapentaenoic acid) under CRISPR/Cas9-mediated knockout of ELOVL5 while supplementation with these fatty acids partially reversed the cellular proliferation and invasion effects of ELOVL5 knockout. Regarding cellular proliferation and invasion, CRISPR/Cas9-mediated knockout of ELOVL5 suppressed the formation of lipid droplets and induced apoptosis via endoplasmic reticulum stress while suppressing renal cancer cell proliferation and in vivo tumor growth. Furthermore, CRISPR/Cas9-mediated knockout of ELOVL5 inhibited AKT Ser473 phosphorylation and suppressed renal cancer cell invasion through chemokine (C-C motif) ligand-2 downregulation by AKT-mTOR-STAT3 signaling. Collectively, these results suggest that ELOVL5-mediated fatty acid elongation promotes not only cellular proliferation but also invasion in RCC.

Laparoendoscopic single-site surgery for urachal remnant with extraperitoneal approach through a suprapubic port.

INTRODUCTION: No standard procedure has been established for laparoendoscopic single-site surgery for urachal remnants (LESS-U). This study aimed to report the novel surgical techniques and initial outcomes of laparoendoscopic single-site surgery with an extraperitoneal approach through a suprapubic port for urachal remnants (spLESS). METHODS: Fifty-five patients (median age, 27 years; range, 15-69 years) who underwent LESS-U were analyzed. To overcome the limitations inherent in the conventional procedure (LESS-U through an umbilical port: uLESS), we modified the port placement and approached via the extraperitoneal space. spLESS is a novel procedure which reduces intestinal damage caused by the extraperitoneal approach and overcomes incomplete resection of the urachal remnant, especially in the bladder dome. Three trocars are inserted into the extraperitoneal space through a suprapubic port in spLESS, and complete resection of the urachal remnant from the umbilicus to the bladder is performed with an appropriate incision line. Patient characteristics and perioperative results were retrospectively collected. Cosmetic outcomes were prospectively evaluated using self-administered questionnaires (body image and photo-series questionnaire). RESULTS: spLESS and uLESS were performed in 43 and 12 patients, respectively. No differences were observed between the perioperative results. The cosmetic outcomes were compared between the groups using body image and photo-series questionnaires. No patient developed major complications; there was no recurrence in either group. CONCLUSIONS: spLESS is a novel procedure which can completely resect the urachal remnant and reduce the risk of intestinal damage. spLESS is a safe, effective, and feasible procedure with high postoperative cosmesis.

ELOVL2 promotes cancer progression by inhibiting cell apoptosis in renal cell carcinoma.

Renal cell carcinoma (RCC) is an aggressive genitourinary malignancy which has been associated with a poor prognosis, particularly in patients with metastasis, its major subtypes being clear cell RCC (ccRCC), papillary PCC (pRCC) and chromophobe RCC (chRCC). The presence of intracellular lipid droplets (LDs) is considered to be a hallmark of ccRCC. The importance of an altered lipid metabolism in ccRCC has been widely recognized. The elongation of very­long­chain fatty acid (ELOVL) catalyzes the elongation of fatty acids (FAs), modulating lipid composition, and is required for normal bodily functions. However, the involvement of elongases in RCC remains unclear. In the present study, the expression of ELOVL2 in ccRCC was examined; in particular, high levels of seven ELOVL isozymes were observed in primary tumors. Of note, elevated ELOVL2 expression levels were observed in ccRCC, as well as in pRCC and chRCC. Furthermore, a higher level of ELOVL2 was significantly associated with the increased incidence of a poor prognosis of patients with ccRCC and pRCC. The CRISPR/Cas9­mediated knockdown of ELOVL2 resulted in the suppression of the elongation of long­chain polyunsaturated FAs and increased LD production in renal cancer cells. Moreover, ELOVL2 ablation resulted in the suppression of cellular proliferation via the induction of apoptosis in vitro and the attenuation of tumor growth in vivo. On the whole, the present study provides new insight into the tumor proliferation mechanisms involving lipid metabolism, and suggests that ELOVL2 may be an attractive novel target for RCC therapy.

Machine learning methods can more efficiently predict prostate cancer compared with prostate-specific antigen density and prostate-specific antigen velocity.

BACKGROUND: Prostate-specific antigen (PSA)-based screening for prostate cancer has been widely performed, but its accuracy is unsatisfactory. To improve accuracy, building an effective statistical model using machine learning methods (MLMs) is a promising approach. METHODS: Data on continuous changes in the PSA level over the past 2 years were accumulated from 512 patients who underwent prostate biopsy after PSA screening. The age of the patients, PSA level, prostate volumes, and white blood cell count in urinalysis were used as input data for the MLMs. As MLMs, we evaluated the efficacy of three different techniques: artificial neural networks (ANNs), random forest, and support vector machine. Model performance was evaluated using area under the receiver operating characteristic curve (AUC) and compared with the PSA level and the conventional PSA-based parameters: PSA density and PSA velocity. RESULTS: When using two annual PSA testing, all receiver operating characteristic curves of the three MLMs were above the curve for the PSA level, PSA density, and PSA velocity. The AUCs of ANNs, random forest, and support vector machine were 0.69, 0.64, and 0.63, respectively. Those values were higher than the AUCs of the PSA level, PSA density, and PSA velocity, 0.53, 0.41, and 0.55, respectively. The accuracies of the MLMs (71.6% to 72.1%) were also superior to those of the PSA level (39.1%), PSA density (49.7%), and PSA velocity (54.9%). Among the MLMs, ANNs showed the most favorable AUC. The MLMs showed higher sensitivity and specificity than conventional PSA-based parameters. The model performance did not improve when using three annual PSA testing. CONCLUSION: The present retrospective study results indicate that machine learning techniques can predict prostate cancer with significantly better AUCs than those of PSA density and PSA velocity.

[Fever, Hepatic Dysfunction and Interstitial Pneumonia Caused by Intravesical Bacillus Calmette-Guerin (BCG) Instillation after Urethral Bougie : A Case Report].

A 60-year-old man had a past history of urothelial carcinoma of the left renal pelvis treated with laparoscopic left total nephroureterectomy in October 2004. He underwent transurethral resection of the bladder tumor (TUR-Bt) twice for recurrence of urothelial carcinoma in the bladder in April 2014 and February 2015, and subsequently received intravesical Bacillus Calmette-Guerin (BCG) instillation at weekly intervalsfor prevention of recurrence. In November 2016, a year and a half after BCG induction, he received BCG therapy after urethral bougie to dilate the urethral stricture. After BCG therapy, he exhibited a continuously high fever. Immediate antituberculosis drug therapy in consideration of BCG sepsis failed to improve the symptoms, and all cultures from urine and blood were negative for mycobacterium tuberculosis. Serum liver enzyme was markedly elevated and chest CT showed diffuse interstitial shadows in both lower lungs. Thus, we considered that these symptoms were caused by a hypersensitivity reaction to BCG and started pulse steroid therapy. After pulse steroid therapy, body temperature, and hepatic function became normal and interstitial pneumonia subsided.

[Metachronous Bilateral Testicular Tumors with Frequently Recurrent Hydrocele : A Case Report].

We report a case of metachronous bilateral testicular tumors combined with hydrocele. A 46-year-old male presented with frequently recurrent left hydrocele. His medical history included a stage IIA right testicular tumor,which had been treated with right high orchiectomy and retroperitoneal lymph node dissection 22 years ago. Magnetic resonance imaging (MRI) showed hydrocele and a low intensity area in the left testis,and the patient underwent left high orchiectomy. After cytological examination of the hydrocele it was categorized as class V,and after a pathological study it was diagnosed as seminoma and embryonal carcinoma. Since postoperative computed tomography showed lung metastasis,treatment with bleomycin,etoposide,and cisplatin (BEP) was indicated. Three courses of BEP produced a complete response. No recurrent testicular tumor was seen at 3 months after the BEP therapy. A metachronous testicular tumor should be considered in patients with a history of testicular tumors who frequently develop recurrent hydrocele.

[Severe Acute Myocardial Infarction during Induction Chemotherapy for Retroperitoneal Germ Cell Tumor : A Case Report].

A 37-year-old man presented at our hospital. Pathological examination of a right orchiectomy specimen, radiographic examination, and tumor marker profile resulted in a diagnosis of retroperitoneal nonseminomatous germ cell tumor (intermediate risk according to IGCC classification). Laboratory testing revealed mild elevation of low density lipoprotein cholesterol. Induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) was started, but he complained of chest pain on day 10 of the second cycle of BEP. We immediately started cardiac monitoring. One hour later, he suffered cardiac arrest due to ventricular fibrillation. Fortunately, sinus rhythm was restored after defibrillation. A diagnosis of acute myocardial infarction (AMI) with total occlusion at the mid-portion of the left anterior descending coronary artery was established by coronary angiography. After percutaneous transluminal coronary angioplasty was successfully performed, he recovered uneventfully. The induction chemotherapy was re-started 19 days after AMI. To avoid endothelial damage by bleomycin, we elected to treat with etoposide, ifosfamide, and cisplatin (VIP). After two further courses of VIP, the patient underwent resection of retoperitoneal tumor and achieved complete remission. The patient has remained disease-free during 3 years follow up without recurrence of AMI.