Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Perinatal clinical course of Vici syndrome associated with novel EPG5 variants: unique cardiac changes and difficulty with foetal diagnosis.

Vici syndrome is a genetic disorder involving autophagy dysfunction caused by biallelic pathogenic variants in ectopic P-granules 5 autophagy tethering factor (EPG5). We report the perinatal clinical course of a neonate with Vici syndrome with a unique cardiac presentation. Foetal ultrasonography (US) detected right ventricular hypertrophy, hypoplastic left ventricle and narrowing of the foramen ovale, which were alleviated after birth. Agenesis of the corpus callosum and cerebellar hypoplasia were missed antenatally. After delivery, the patient was clinically diagnosed with Vici syndrome and two novel pathogenic mutations were detected in EPG5 The T-cell receptor repertoire was selectively skewed in the Vß2 family. Immunological prophylaxis and tube feeding were introduced. Early diagnosis helps parents accept their child's prognosis and decide on a care plan. However, US has limited potential to detect clinical phenotypes associated with Vici syndrome. Foetal MRI may detect the characteristic abnormalities and contribute to antenatal diagnosis.

Fusion imaging of single-photon emission computed tomography and magnetic resonance lymphangiography for post-Fontan chylothorax.

A preschool male patient with an extensive cardiac surgical history developed refractory chylothorax after a total cavopulmonary connection. Neither lymphoscintigraphy nor single-photon emission computed tomography (SPECT)/computed tomography could identify the lymphatic system leakage sites. Non-contrast heavy T2-weighted magnetic resonance lymphangiography (MRL) was performed to visualize the lymphatic system. Nevertheless, distinguishing lymphatic ducts from other watery structures of the patient remained difficult. Therefore, non-contrast MRL and SPECT images were fused. This hybrid diagnostic tool elucidated the pathophysiology of the prolonged chylothorax; pulmonary lymphatic perfusion syndrome and illustrated the anatomical connection of the thoracic duct and an abnormally dilated lymphatic network in the neck and left hilar regions. Subsequent intranodal lymphangiography with ethiodized oil confirmed these findings. SPECT/MRL may become an alternative modality for revealing the mechanism of prolonged chylothorax by visualizing the lymphatic system when dynamic contrast-enhanced magnetic resonance lymphangiography is unavailable.

Enzalutamide Versus Abiraterone plus Prednisolone Before Chemotherapy for Castration-resistant Prostate Cancer: A Multicenter Randomized Controlled Trial.

Background: Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for patients with CRPC remains unclear. Objective: To evaluate whether ENZ or ABI is better as first-line treatment for CRPC. Design setting and participants: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. The study enrolled 203 patients with CRPC before chemotherapy between February 20, 2015, and July 31, 2019. Patients were randomly assigned 1:1 to the ENZ or ABI arm. Outcome measurements and statistical analysis: The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included the PSA response rate (≥50% decline from baseline), overall survival, and safety. A log-rank test was used for comparison of survival analyses between arms. Results and limitations: After randomization, 92 patients in each arm were treated and analyzed. Time to PSA progression did not significantly differ between the arms (median 21.2 mo for ENZ and 11.9 mo for ABI; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.51-1.27; p = 0.1732). There was a significant difference in the PSA response rate between the arms (72% for ENZ and 57% for ABI; p = 0.0425). There was no significant difference in overall survival (median 32.9 mo for ENZA and 35.5 mo for ABI; HR 1.17, 95% CI 0.72-1.88; p = 0.5290). Grade ≥3 adverse events were observed in 11% of patients in the ENZA arm and 21% in the ABI arm (p = 0.1044). Conclusions: ENZ did not show any survival benefit in comparison to ABI, but showed a better PSA response rate with a low rate of severe adverse events in CRPC. Patient summary: Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.

Thrombus calcification after removing peripherally inserted central catheters in extremely preterm infants.

Pericatheter thrombus calcification is a complication that arises due to central venous catheter insertion and is particularly rare in peripherally inserted central catheters (PICCs). In this case report, we reviewed the clinical course of two neonates experiencing thrombus calcification. The first case involved a male neonate weighing 445 g. His PICC dwelt in the superior vena cava for over 49 days. Although a radiograph after removal did not show any silhouette, subsequent radiographs and CT depicted a catheter-like outline. Percutaneous intravascular retrieval was performed to salvage the object. Pathological examination revealed it to be a calcified cast. The calcified thrombosis was successfully dissolved with 6 months of warfarin therapy. The second case involved a male neonate weighing 534 g. After PICC removal, a catheter-like structure was shown on ultrasonograms. It was determined that invasive procedures were unnecessary for diagnosing the calcified thrombosis based on experience with the first case.

Test clamp procedure in robot-assisted partial nephrectomy: is it a safe procedure?

We performed test clamp procedure in robot-assisted partial nephrectomy (RAPN) to prevent massive bleeding during tumor resection and to omit dissection of non-feeding arteries around the tumor. We subsequently analyzed the safety and usefulness of the procedure. The Test clamp procedure was performed for 1 to 3 min during renal artery test ischemia prior to the actual ischemia and tumor resection. We confirmed the disappearance of blood flow around the renal tumor using color Doppler ultrasonography. If arterial blood flow around the tumor remained, we surveyed the site for other arteries that needed to be clamped and repeated the test clamp procedure until renal blood flow around the tumor disappeared. We retrospectively analyzed consecutive RAPN cases performed from July 2016 to March 2020 at our institutions and reviewed medical records. The clinical data of the RAPN cases were statistically analyzed. Sixty-four RAPN cases underwent the test clamp procedure, which was categorized as the TEST group. Test clamping was performed safely without any clamping-related complications in all cases. Eleven cases (17%) underwent partial ischemia, which was a significantly higher number than that in the control group. Massive bleeding during tumor resection was more frequent in the control group. Postoperative deterioration of estimated glomerular filtration rate did not differ significantly between both groups. Although further investigation was still necessary, our findings indicate that the test clamp procedure may be a safe and secure procedure to perform in RAPN for both patients and surgeons.

A novel risk classification score for malignant ureteral obstruction: a multicenter prospective validation study.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P < 0.0001). In 217 patients with ureteral stenting, median ureteral stent failure-free survival times of good, intermediate, and poor risk groups were 385, 183, and 57 days, respectively (P < 0.0001). Limitations include the limited ethnicity and the extended duration of study enrollment. The novel PLaCT risk classification score could divide MUO patients into three risk groups with distinct survival times and ureteral stent patencies. This score will aid in establishing prognosis and treatment strategy for all physicians engaged in cancer treatment.

Effectiveness of Synthetic Polymer-coated Peripherally Inserted Central Catheter in Patients With Advanced Cancer.

BACKGROUND/AIM: A peripherally inserted central catheter (PICC) is recommended for the safe administration of anticancer agents. The effectiveness of synthetic polymer-coated and non-coated PICCs was compared. PATIENTS AND METHODS: Patients with advanced cancers who had indwelling PICCs were reviewed using their medical records. Three types of PICCs were compared in terms of complications and catheter failure. RESULTS: A total of 90 patients were retrospectively analyzed, including 31 with Groshong PICCs, 30 with Argyle PICC kit, and 29 with Argyle PICC kit II. The incidence of catheter failure for Groshong PICC, Argyle PICC kit, and Argyle PICC kit II per 1,000 PICC days was 4.4614, 5.6617, and 0.8658, respectively. Catheter failure-free survival in the Argyle PICC kit II group was significantly better than that in the Argyle PICC kit group (p=0.0339). CONCLUSION: Argyle PICC kit II, a synthetic polymer-coated PICC, may render longer patency and prevention of catheter failure than non-coated PICCs.

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): a study protocol for a multicenter randomized phase III trial.

BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. METHODS/DESIGN: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. DISCUSSION: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014.

Stone Attenuation Values Measured by Average Hounsfield Units and Stone Volume as Predictors of Total Laser Energy Required During Ureteroscopic Lithotripsy Using Holmium:Yttrium-Aluminum-Garnet Lasers.

OBJECTIVE: To evaluate the predictors of the total laser energy (TLE) required during ureteroscopic lithotripsy (URS) using the holmium:yttrium-aluminum-garnet (Ho:YAG) laser for a single ureteral stone. MATERIALS AND METHODS: We retrospectively analyzed the data of 93 URS procedures performed for a single ureteral stone in our institution from November 2011 to September 2015. We evaluated the association between TLE and preoperative clinical data, such as age, sex, body mass index, and noncontrast computed tomographic findings, including stone laterality, location, maximum diameter, volume, stone attenuation values measured using average Hounsfield units (HUs), and presence of secondary signs (severe hydronephrosis, tissue rim sign, and perinephric stranding). RESULTS: The mean maximum stone diameter, volume, and average HUs were 9.2 ± 3.8 mm, 283.2 ± 341.4 mm3, and 863 ± 297, respectively. The mean TLE and operative time were 2.93 ± 3.27 kJ and 59.1 ± 28.1 minutes, respectively. Maximum stone diameter, volume, average HUs, severe hydronephrosis, and tissue rim sign were significantly correlated with TLE (Spearman's rho analysis). Stepwise multiple linear regression analysis defining stone volume, average HUs, severe hydronephrosis, and tissue rim sign as explanatory variables showed that stone volume and average HUs were significant predictors of TLE (standardized coefficients of 0.565 and 0.320, respectively; adjusted R2 = 0.55, F = 54.7, P <.001). CONCLUSION: Stone attenuation values measured by average HUs and stone volume were strong predictors of TLE during URS using Ho:YAG laser procedures.

Massive Ascites in a Renal Transplant Patient after Laparoscopic Fenestration of a Lymphocele.

Retroperitoneal lymphocele is a common complication of renal transplantation. Here, we report the case of a 67-year-old woman with massive ascites after fenestration surgery for a lymphocele that developed following renal transplantation. She had been on continuous ambulatory peritoneal dialysis for 9 years. Living donor renal transplantation was performed and an intrapelvic lymphocele subsequently developed. The lymphocele did not resolve after aspiration therapy; therefore, laparoscopic fenestration was performed. Although the lymphocele disappeared, massive ascites appeared in its stead. Half a year later, the ascites was surgically punctured, which then gradually resolved and disappeared 6 weeks later. Aspiration therapy should be considered in patients on long-term peritoneal dialysis, although laparoscopic fenestration is safe and effective.

Holmium Laser Enucleation of the Prostate With Percutaneous Nephrostomy Into the Transplanted Kidney in Patient With Severe Benign Prostatic Hyperplasia With Vesicoureteral Reflux - A Case Report.

A 66-year-old male, who had received renal transplantation 10 years before, was admitted to our hospital with urinary retention. The prostate volume was 169.2 ml. Furthermore, grade 5 vesicoureteral reflux (VUR) was shown in the cystography. Holmium laser enucleation of prostate (HoLEP) was performed, and percutaneous nephrostomy to the transplanted kidney was performed simultaneously to prevent from severe perioperative infection. After that, renal graft function improved and no urinary retention reoccurred, although surgical repair against VUR was necessary 10 months after HoLEP. We conclude that surgical treatment for BPH after kidney transplantation should be strongly considered with care for infections.

Isolated torsion of the fallopian tube in a menopausal woman and a pre-pubertal girl: two case reports.

INTRODUCTION: Isolated torsion of the fallopian tube without an ovarian abnormality is an uncommon event, with an incidence of approximately 1 in 1,500,000 females. Isolated torsion of the fallopian tube occurs mostly in reproductive-aged women, and is thus extremely rare in menopausal women and pre-pubertal girls. CASE PRESENTATIONS: In case 1, 63-year-old Japanese woman presented with a 2-day history of acute lower abdominal pain. Menopause occurred at 53 years of age. Pelvic ultrasonography showed an enlarged mass (73 × 47 mm) on the right side of her uterus. An urgent laparoscopy was performed based on a presumptive diagnosis of right ovarian tumor torsion. During the laparoscopy, we noted a black, necrotic, solid tumor arising from the distal end of her right fimbria. Her right fallopian tube was twisted with the tumor, but her right ovary was normal and not involved. A laparoscopic tumorectomy with a right salpingectomy was performed. Her post-operative course was uneventful. In case 2, a 10-year-old Japanese girl presented with a 1-day history of lower abdominal pain associated with nausea and vomiting. Menarche had occurred 2 months earlier. A computed tomography and magnetic resonance imaging examination demonstrated a dilated tubal cystic mass with a normal uterus and bilateral ovaries. An urgent laparoscopy was performed based on a presumptive diagnosis of right fallopian tube torsion. During laparoscopy, her right fallopian tube was noted to be dark red, dilated, and twisted several times. Her right fimbria was necrotic-appearing and could not be preserved. Therefore, a laparoscopic right salpingectomy was performed. A histologic examination revealed ischemic changes with congestion of her right fallopian tube, which was consistent with tubal torsion. She had an uncomplicated post-operative course. CONCLUSION: We have presented two very rare cases of isolated fallopian tubal torsion. Radiologic interventions, such as computed tomography and magnetic resonance imaging, in addition to ultrasonography, are helpful diagnostic tools. Isolated torsion of the fallopian tube should be considered in the differential diagnosis of lower abdominal pain with a cystic mass and a normal ipsilateral ovary in all female patients, regardless of age.

Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

INTRODUCTION: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. CASE PRESENTATION: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. CONCLUSION: We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

Spontaneous retroperitoneal hemorrhage caused by rupture of an ovarian artery aneurysm: a case report and review of the literature.

INTRODUCTION: Spontaneous rupture of an ovarian artery aneurysm is extremely rare. Although a majority of these cases have been associated with pregnancy, there have been recent reports and reviews of rare cases that were not directly associated with pregnancy. Transcatheter arterial embolization is considered to be an alternative therapy to surgery. CASE PRESENTATION: A 44-year-old Japanese woman, gravida 3 para 3, presented to our emergency room complaining of intermittent right flank pain. She had undergone a cesarean section 2 years previously, and had no history of abdominal trauma. On admission, her blood pressure was 115/78 mmHg, pulse 70 beats per minute, and hemoglobin concentration 9.8 g/dL. Abdominal ultrasonography and contrast-enhanced dynamic computed tomography revealed a large retroperitoneal hematoma. Findings on three-dimensional computed tomography angiography suggested ruptured aneurysm of her right ovarian artery. A selective right ovarian artery angiogram revealed a tortuous aneurysm. Transcatheter arterial embolization using N-butyl-2-cyanoacrylate was performed. The aneurysm was successfully embolized, and her course after embolization was uneventful. She has remained symptom-free during 3 months of follow-up. CONCLUSIONS: This was a very rare case of a patient who had a retroperitoneal hemorrhage originating from an ovarian artery aneurysm. A review of published case reports found that contrast-enhanced computed tomography with reconstruction images is an excellent imaging tool. Diagnostic angiography and subsequent transcatheter arterial embolization are thought to be very effective for this condition.

A novel therapeutic strategy for chylous ascites after gynecological cancer surgery: a continuous low-pressure drainage system.

PURPOSE: Postoperative chylous ascites is an unusual complication following retroperitoneal surgery. A search of the English literature showed only 44 cases of chylous ascites following gynecological cancer surgery. The treatment is primarily conservative, but surgical treatment is considered in resistant cases. We developed a novel non-surgical therapeutic strategy for postoperative chylous ascites. METHODS: We report a case of severe chylous ascites following pelvic lymph node dissection for gynecological cancer. RESULTS: Total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washing, and systematic pelvic lymph node dissection were performed for a stage II G1 endometrioid adenocarcinoma (FIGO 2009). Forty-one days after surgery, the patient was readmitted due to massive ascites. Repeated paracentesis and a low-fat diet were only partially effective. Fifty-one days after surgery, we started paracentesis with a continuous low-pressure drainage system. Nine days later, there was no further fluid drainage. The patient was asymptomatic and without recurrent disease at follow-up 3 months later. CONCLUSIONS: Pelvic lymph node dissection may cause postoperative chylous ascites. Paracentesis with a continuous low-pressure drainage system can be an effective conservative treatment for postoperative chylous ascites.

The effectiveness of interferon-alpha subtypes alternation for metastasis from renal cell carcinoma.

Interferon-alpha (IFN-α) has been used in systemic treatment for metastatic renal cell carcinoma (mRCC). IFN-α has at least 14 subtypes, each of which has different biological activity. There have been reports that mRCC resistant to an IFN-α treatment responded to another IFN-α subtype. This study was performed to evaluate the effectiveness of alternation of different IFN-α subtypes for mRCC that did not respond to initial IFN-α treatment. In our department and associated institutions, alternating therapy of IFN-α was provided for 15 initial IFN-α refractory mRCC cases from June 2005 to September 2008. Among the 15 patients, the effects of alternating IFN-α therapy were as follows: complete response (CR), 0 cases; partial response (PR), 1 case; stable disease (SD), 3 cases; progressive disease (PD), 11 cases. The response rate (CR+PR) was 7% and disease control rate (CR+PR+SD) was 27%. No severe side effects were observed in any of these cases. The PR case is still in PR 21 months after alternating IFN-α therapy. Among the three SD cases, one has continued SD for 14 months and the other for 12 months. Alternating IFN-α therapy for mRCC can be attempted even if other cytokines are not effective.

Down-regulation of calcium/calmodulin-dependent protein kinase kinase 2 by androgen deprivation induces castration-resistant prostate cancer.

BACKGROUND: Conversion into androgen-hypersensitive state and adaptation to the low concentration of androgen during ADT cause relapse of prostate cancer (PCa). It is important to identify differentially expressed genes between PCa and normal prostate tissues and to reveal the function of these genes that are involved in progression of PCa. METHODS: We performed cDNA microarray analysis to identify differentially expressed genes, calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2). Immunohistochemical analysis was conducted to investigate the relationship between the CAMKK2 expression level and prognosis. The function of CAMKK2 was assessed by generating CAMKK2 overexpressed LNCaP cells and by knockdown of CAMKK2. RESULTS: We identified CAMKK2 overexpressed six times in PCa more than normal prostate by cDNA microarray analysis. Immunohistochemical analysis of CAMKK2 protein showed that CAMKK2 protein was expressed more in PCa than normal tissue. However, the expression in the high-grade PCa diminished. Moreover, the narrowness of CAMKK2-positive area before ADT was a poor prognostic factor. Androgen-deprivation treatment from the medium in which LNCaP cells were cultured in the presence of 10 nM DHT repressed CAMKK2 expression. CAMKK2 overexpressed LNCaP cells (LNCaP/GFP-CAMKK2) attenuated androgen-sensitivity. Tumorigenesis of LNCaP/GFP-CAMKK2 cells in male SCID mice was decreased compared with control cells irrespective of castration. Finally, knockdown of CAMKK2 mRNA in LNCaP cells induced androgen-hypersensitivity and stimulated LNCaP cell proliferation. CONCLUSIONS: Induction of androgen-hypersensitivity after ADT may be involved in down-regulation of CAMKK2. This result may provide new therapeutic approach to keep androgen-sensitivity of PCa after ADT.

Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis.

OBJECTIVE: To examine whether bone turnover markers could be predictive markers of the probability of newly arising skeletal-related events (SRE) after the start of zoledronic acid treatment in patients with prostate cancer with bone metastasis. PATIENTS AND METHODS: In all, 30 patients with prostate cancer with bone metastasis were treated with zoledronic acid infusion every 4 weeks. Serum C-terminal crosslinking telopeptide of type 1 collagen (1CTP), bone alkaline phosphatase (BAP), and prostate-specific antigen (PSA) levels were measured at the start of zoledronic acid treatment to establish baseline values, and every 4 weeks thereafter. To judge in the early phase whether zoledronic acid is effective in these patients, we retrospectively compared 1CTP, BAP, and PSA levels at 1, 3, and 6 months after starting zoledronic acid treatment with those at baseline. RESULTS: SRE-free survival of patients with increases of 1CTP levels at 1 and 3 months and BAP levels at 3 months were significantly poorer than those of patients with decreases in 1CTP or BAP levels (P = 0.001, P = 0.042, and P = 0.004, respectively). Overall survival of patients with increases of 1CTP levels at 1 and 3 months and of BAP levels at 6 months were significantly poorer than those of patients with decreases of 1CTP or BAP levels (P = 0.013, P = 0.027, and P = 0.035, respectively). CONCLUSION: The measurement of 1CTP and BAP levels at an early phase after starting zoledronic acid treatment may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan.

Clinicopathological outcomes of clinical T1a renal cell carcinoma by tumor size.

OBJECTIVE: We performed a retrospective review of clinical T1a renal cell carcinoma patients treated in our institution. The clinicopathological findings and patients' prognoses were analyzed according to tumor size, and risk factors for tumor recurrence were elucidated. METHODS: A total of 140 cases of sporadic renal cell carcinoma with a diameter of 4 cm or less on computed tomography findings for preoperative evaluation were treated as clinical T1a. Patients underwent radical nephrectomy or nephron-sparing surgery, and were evaluated postoperatively every 3-6 months to screen for metastatic disease. Patients' medical records were reviewed retrospectively and the status of each patient was assessed. RESULTS: There were four cases of clinically metastatic disease at diagnosis. There were no correlations between tumor size and pathological stage, Fuhrman nuclear grade or histological type. The rate of cases with microvascular invasion on pathological findings increased according to tumor diameter. Disease recurrence occurred in six patients (5.7%) during a mean postoperative follow-up of 41.7 months. There was a significant difference in the recurrence-free rate between pT1a patients with a tumor diameter of 31 mm or more and other patient groups. In terms of microvascular invasion on histological findings, the probability of non-recurrence at 7 years was 0% for patients with and 92.9% for those without microvascular invasion. CONCLUSIONS: Among T1a renal cell carcinoma, tumors over 30 mm in diameter may have aggressive biological potential, possibly due to microvascular invasion. Long-term follow-up is needed for these tumors.