Laparoendoscopic single-site nephrectomy for hemodialysis patients with dialysis-related renal tumors.

PURPOSE: The purpose of this study is to assess the efficacy of laparoendoscopic single-site (LESS) nephrectomy in hemodialysis patients, we compared outcomes between LESS nephrectomy and conventional laparoendoscopic nephrectomy in hemodialysis patients with dialysis-related renal tumors. MATERIAL AND METHODS: A total of 16 hemodialysis patients who underwent LESS nephrectomy (LESS-N; n = 8) or conventional laparoendoscopic nephrectomy (C-N; n = 8) between November 2003 and July 2012 were retrospectively evaluated. Outcomes were compared between the two groups. RESULTS: Patient and tumor characteristics were similar between the LESS-N and C-N groups. The mean operative duration was longer in the LESS-N than in the C-N group (231.0 ± 26.7 min versus 188.6 ± 36.4 min; p = .025). The mean estimated blood loss was lower in the LESS-N compared with the C-N group (26.4 ± 14.4 ml versus 65.6 ± 45.2 ml; p = .047). Postoperative complications were observed in three cases, comprising one case of retroperitoneal hematoma in the LESS-N group and one case each of peritoneal hematoma and retroperitoneal abscess in the C-N group. Surgical scarring was minimal in the LESS-N group. CONCLUSIONS: Although there is a little extension of the operating time, LESS nephrectomy in hemodialysis patients is a feasible procedure compared with the conventional method.

Pfannenstiel laparoendoscopic reduced-port bilateral radical nephrectomy for a patient with renal cell carcinoma undergoing hemodialysis.

We performed Pfannenstiel laparoendoscopic reduced-port bilateral radical nephrectomy on a patient with renal cell carcinoma undergoing hemodialysis. A 4-cm Pfannenstiel incision was made, and a GelPOINT access was inserted. Three trocars were placed through the access platform, and additional 5- and 3-mm trocars were inserted in the umbilicus and paraumbilical area, respectively. After left nephrectomy, right nephrectomy was successfully completed in 401 min, with an estimated blood loss of 70 mL. There were no intraoperative or postoperative complications, and the patient was discharged 10 days postoperatively. The umbilical scar was concealed within the umbilical fold, and the scar from the 3-mm trocar was almost invisible. The Pfannenstiel scar was minimal and concealed by the patient's underwear. Pfannenstiel laparoendoscopic reduced-port simultaneous bilateral radical nephrectomy is a safe and technically feasible procedure that offers great cosmesis for patients with bilateral renal tumors and end-stage renal disease.

Hypoxia-induced angiopoietin-like protein 4 as a clinical biomarker and treatment target for human prostate cancer.

Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional protein, playing roles in glucose and lipid metabolism, inflammation, angiogenesis, and tumorigenesis. Recent research suggests that ANGPTL4 is induced by hypoxia and is a useful diagnostic or prognostic marker for various cancers. However, it remains unclear whether ANGPTL4 expression influences prostate cancer. Here we examined the biological and clinical relevance of ANGPTL4 expression in prostate cancer. Firstly we examined ANGPTL4 expression in the prostate cancer cell lines LNCaP and LNCaP/CH incubated at 1% O2 for at least 6 months. We compared cellular proliferation, migration, and ANGPTL4 secretion in a culture medium between these cell lines. In addition, we investigated the effect of various concentrations of recombinant ANGPTL4 protein (rANGPTL4) on cellular proliferation and intracellular signaling pathways. Moreover, we used ANGPTL4 knockdown by RNA interference to investigate the influence of ANGPTL4 expression on these cell lines. Finally, we investigated the correlation between ANGPTL4 expression in prostate cancer specimens and clinicopathological parameters using immunohistochemistry. Our data suggested that the expression of ANGPTL4 in hypoxic conditions was 14.4-fold higher than that in normoxic condition. ANGPTL4 secretion in the culture medium increased 7.0-fold. In addition, rANGPTL4 increased cellular proliferation 1.72-fold via Akt activation. Moreover, ANGPTL4 knockdown decreased cell growth and its secretion by 25.7 and 41.4%, respectively, compared with the control. A multivariate analysis showed that positive ANGPTL4 expression in the resected specimens was an independent prognostic indicator of biochemical recurrence (P=0.03, hazard ratio = 2.02). Our results show that ANGPTL4 is induced by hypoxia and promotes cancer progression via the activated PI3K/Akt pathway. Moreover, ANGPTL4 can be used as a prognostic marker for prostate cancer patients undergoing radical prostatectomy.

Patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical laparoendoscopic single-site adrenalectomy.

INTRODUCTION: Laparoendoscopic single-site surgery is a recently innovated urologic surgical procedure. Transumbilical laparoendoscopic single-site adrenalectomy (LESS-A) is technically safe and feasible in patients with benign adrenal tumors. To improve patient counseling and informed consent, we evaluated patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical LESS-A. METHODS: We reviewed 24 patients who underwent transumbilical LESS-A and assessed their operative and esthetic outcomes and incisional pain. Incisional pain was evaluated using a 10-point visual analog scale, and the body image and cosmetic satisfaction were measured using a questionnaire that included a body image scale (range, 5-20 points) and a cosmetic scale (range, 3-24 points). RESULTS: Pure LESS-A was performed on 10 patients using a multichannel port; an additional 5-mm trocar was used in two obese patients. Supplementary to the single-incision approach, one or two 3-mm ports were used in 12 patients. The mean operative time was 203 min; the mean blood loss was 41 mL. The mean pain visual analog scale scores on postoperative days 1, 3, and 7 were 3.5, 2.2 (P = 0.012), and 1.5 points (P = 0.018), respectively. The mean body image scale and cosmetic scale scores indicating wound satisfaction 1 month after the surgery were 20 and 22 points, respectively. Although one patient had liver injury during surgery, the postoperative course during the 3-month follow-up was uneventful. CONCLUSION: Transumbilical LESS-A confers less postoperative pain and better cosmetic satisfaction than conventional laparoscopic adrenalectomy. Therefore, this procedure could potentially become a standard treatment option for benign adrenal tumors.

Composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of medullary thyroid carcinoma in a patient with multiple endocrine neoplasia type 2B: A case report.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome with major components of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. MEN2B is the most aggressive and rarest of the MEN2 variants. Pheochromocytoma in MEN2 is virtually always located in the adrenal medulla, but MEN2-associated extra-adrenal pheochromocytomas (paraganglioma) are rare. A 59-year-old man who has been diagnosed with MEN2B consulted our hospital for surgical treatment of a 10-mm left adrenal mass and a 30-mm retroperitoneal mass. He had paroxysmal elevations in blood pressure and in urinary metanephrine and vanillylmandelic acid values. Laparoscopic excision of the left adrenal gland and retroperitoneal mass was performed. We experienced an extremely rare case of composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of medullary thyroid carcinoma in a patient with MEN2B.

Pfannenstiel laparoendoscopic reduced-port radical nephrectomy.

INTRODUCTION: We previously reported cases of laparoendoscopic single-site nephrectomy performed through an umbilical or pararectal incision. To improve cosmesis and operability, we performed three Pfannenstiel laparoendoscopic reduced-port nephrectomies. MATERIALS AND SURGICAL TECHNIQUE: In the first case, a GelPOINT access was placed through a 2-cm umbilical incision, and two additional 3-mm trocars were inserted. The specimen was extracted through a 4-cm Pfannenstiel incision. In the second and third cases, a GelPOINT access was placed through a 5-cm Pfannenstiel incision, and two additional 3-mm trocars were inserted. The specimens were extracted without additional skin incisions. In all cases, the endoscope and vessel-sealing device were inserted through the GelPOINT access. We used 3-mm scissors, dissecting forceps, and bipolar forceps. DISCUSSION: The operating time and estimated blood loss were 228, 280, and 155 min and 10, 410, and 5 mL, respectively. There were no intraoperative or postoperative complications. The 3-mm forceps showed similar efficacy as the conventional 5-mm forceps. Therefore, a Pfannenstiel reduced-port nephrectomy using 3-mm working trocars is a safe and feasible procedure with good cosmesis.

Improvement of renal function by changing the bone-modifying agent from zoledronic acid to denosumab.

BACKGROUND: In order to help in selecting the optimum bone-modifying agent (BMA; zoledronic acid or denosumab), we investigated the impact of the BMA on the renal function of patients with bone metastases. MATERIALS AND METHODS: The present study consisted of 118 patients who were treated with denosumab for bone metastases secondary to prostate cancer, renal cell cancer, and urothelial cancer at our hospital between 2012 and 2015. The clinical course of the renal function of these patients, treated with zoledronic acid or denosumab, was retrospectively evaluated. RESULTS: Of the 118 patients who were treated with denosumab during the study period, 57 (48 %) had previously been administered zoledronic acid and 61 (52 %) had received denosumab as the first-line BMA. The reasons for changing from zoledronic acid to denosumab were increased creatinine serum level (26 patients, 46 %), patient preference (16 patients, 28 %), difficulty with venous infusion (10 patients, 17 %), and other reasons (5 patients, 9 %). The median level of creatinine clearance in the patients who changed from zoledronic acid to denosumab due to increased serum creatinine level was 59.9 ml/min before administration of zoledronic acid, 40.9 ml/min at the beginning of denosumab treatment, 47.5 ml/min at 3 months after administration of denosumab, and 52.0 ml/min at the last follow-up. There were significant differences. CONCLUSIONS: For the first time, we demonstrated that the renal function of some patients, which had deteriorated following zoledronic acid administration, successfully improved after changing to denosumab.

Efficacy and Safety Profile of Enzalutamide for Japanese Patients with Castration-resistant Prostate Cancer.

Enzalutamide is a novel, non-steroidal anti-androgen that was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) in 2014 in Japan. To assess the potency of enzalutamide treatment in Japan, we performed a pilot retrospective study. Among 91 patients who received treatment in our Institution between May 2014 and July 2015, 51 patients with docetaxel-naïve CRPC (56.0%) underwent enzalutamide therapy. The median progression-free survival (PFS) and overall survival (OS) were 10.2 months and 27.9 months, respectively. The remaining 40 patients with CRPC (44.0%) underwent enzalutamide therapy after docetaxel. The median PFS and OS were 4.4 months and not reached, respectively. Among patients with docetaxel-naïve CRPC, 12 (24%) experienced adverse events, whereas 16 (40%) experienced adverse events after docetaxel. Fatigue (15%) and appetite loss (13%) were the most common. We partially clarified the characteristics of enzalutamide therapy in Japan. The PFS associated with enzalutamide might be shorter in Japanese patients.

Angiopoietin-like protein 2 induces androgen-independent and malignant behavior in human prostate cancer cells.

Angiopoietin-like proteins (ANGPTLs), which comprise 7 members (ANGPTL1-ANGPTL7), structurally resemble angiopoietins. We investigated the roles of ANGPTLs in the acquisition of androgen independence and the malignant behavior of human prostate cancer cells. Expression of ANGPTL messenger RNA (mRNA) and proteins were ascertained using RT-qPCR and western blot analysis in human prostate cancer cell lines. Androgen­dependent LNCaP and androgen-independent LNCaP/AI cells, respectively, were cultured in fetal bovine and charcoal-stripped medium. Cell proliferation, androgen dependence, migration and invasion, respectively, were examined under the overexpression and knockdown of ANGPTL2 by transfection of ANGPTL2 cDNA and its small­interfering RNA (siRNA). The effects of exogenous ANGPTL2 and blocking of its receptor, integrin α5ß1, were also investigated. Human prostate cancer cell lines predominantly expressed ANGPTL2 among the members. Interrupting ANGPTL2 expression with siRNA suppressed the proliferation, migration and invasion of LNCaP cells. LNCaP/AI cells showed a higher ANGPTL2 expression than that of LNCaP cells. Furthermore, siRNA led to apoptosis of LNCaP/AI cells. The ANGPTL2-overexpressing LNCaP cells markedly increased proliferation, epithelial-to-mesenchymal transition (EMT) and malignant behavior in androgen­deprived medium. The migration rates were increased depending on the concentration of ANGPTL2 recombinant protein and were inhibited by anti-integrin α5ß1 antibodies. To the best of our knowledge, this is the first study to elucidate the expression of ANGPTL2 in human prostate cancer cells. ANGPTL2 may be important in the acquisition of androgen independency and tumor progression of prostate cancer in an autocrine and/or paracrine manner via the integrin α5ß1 receptor. Targeting ANGPTL2 may therefore be an efficacious therapeutic modality for prostate cancer.

[Elucidating the molecular mechanism of prostate cancer progression under chronic hypoxia and development of the novel therapeutic approach].

Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.