[Comparison of Surgical Outcome of Laparoscopic Sacrocolpopexy between the Novice and Experienced Surgeon in Laparoscopic Surgery].

We retrospectively analyzed the safety and surgical outcomes of laparoscopic sacrocolpopexy (LSC) by the novice surgeon (performed ＜5 laparoscopic surgery). Between November 2017 and December 2020, there were 15 cases in which the novice surgeon performed part of LSC, 8 cases in which the novice performed all of LSC, and 50 cases in which the experienced surgeon (performed ＞100 laparoscopic surgery) performed all of LSC. We compared surgical outcome of the 50 cases operated by the experienced surgeon and 23 cases operated by the novice. The laparoscopic time was longer when performed by the novice than by the experienced surgeon (median 208 minutes vs 189 minutes, p＝0.039). Cases of pelvic organ prolapse quantification system (POP-Q) stage 4 were operated more often by the experienced surgeon than by the novice (28% vs 4.8%, p＝0.027). There were no significant differences in the complications and recurrence of pelvic organ prolapse (POP-Q≧2). The LSC process was divided into five steps. The laparoscopic time of all steps was longer when performed by the novice than by the experienced surgeon except the step of lifting up the sigmoid colon and hysterectomy. As the number of cases performed by the novice increased, the laparoscopic time of all steps decreased. The short-term surgical outcomes for cases operated by the novice and experienced surgeon were comparable when the novice avoided cases of POP-Q stage 4. LSC has been said to be difficult, but in this study, even novice surgeons in laparoscopic surgery may be able to perform LSC by accumulating cases. Although this study is not generalizable due to limitations, we believe it will inspire many young doctors to perform LSC.

Hydronephrosis severity as a predictor of postoperative renal function decline following laparoscopic radical nephroureterectomy.

BACKGROUND: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). METHODS: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. RESULTS: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. CONCLUSION: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.

Preoperative risk classification for intravesical recurrence after laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma in a multi-institutional cohort.

INTRODUCTION: This study aimed to identify preoperative risk factors and create a risk classification for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy in a multi-institutional cohort. METHODS: We retrospectively analyzed 283 patients who had undergone laparoscopic radical nephroureterectomy for nonmetastatic upper tract urothelial cancer between March 2002 and March 2020. The cumulative incidence of intravesical recurrence for 224 patients without previous or concomitant bladder cancer was examined using multivariate Fine-Gray competing risks proportional hazards models. A risk stratification model was created to predict subsequent patient outcomes based on the results. RESULTS: The median follow-up duration was 33.3 months, and 71 (31.7%) patients experienced intravesical recurrence. The estimated cumulative incidence of intravesical recurrence at one and 5 years was 23.5% and 36.4%, respectively. In multivariate analysis, the presence of ureter tumors and multiple tumors were shown to be independently significant predictive factors for intravesical recurrence. Based on the results, we classified patients into three risk groups. The cumulative incidence rates of intravesical recurrence within 5 years after surgery were 24.4%, 42.5%, and 66.7% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: We identified risk factors and created a risk classification model for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy. Based on this model, an individualized surveillance protocol or adjuvant therapy could be provided.

Atypical Oncologic Failure After Laparoscopic Radical Nephroureterectomy in a Japanese Multicenter Study.

Objectives: To investigate the recurrence patterns and the atypical oncologic failure (AOF) defined as the presence of atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, after laparoscopic radical nephroureterectomy (LRNU). Methods: LRNU performed at three institutions were included in this retrospective study. The primary endpoints were the first recurrence site and recurrence-free survival. The recurrence sites were classified as atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, as well as distant, local, and intravesical. The Kaplan-Meier curves were obtained to elucidate the time until recurrence and survival. Results: A total of 283 patients were included in the final analysis. Postoperative pathology was T3 or higher in 112 (40%) patients. The median follow-up period was 31 months, and the 3-year recurrence-free, cancer-specific, and overall survival rates were 69.6%, 78.1%, and 72.0%, respectively. The first recurrence sites involved distant, local, atypical, and intravesical recurrences in 51 (18%), 36 (13%), 14 (5%), and 94 (33%) patients, respectively. Of the 14 patients with AOF, 12 had pathologically locally advanced tumors, but seven patients had a preoperative diagnosis of clinical stage T2 or less. Conclusion: A small number of AOF cases were found after LRNU for patients with upper tract urothelial carcinoma. Careful patient selection is critical for AOF prevention.

Clinical outcomes following laparoscopic radical nephroureterectomy in octogenarians.

BACKGROUND: This study aimed to compare the incidence of postoperative complications occurring within 30 days of surgery between octogenarians and younger patients and identify preoperative risk factors for the incidence of postoperative complications. Moreover, we also compared the oncological outcomes between octogenarians and younger patients. METHODS: This retrospective study included 283 patients who underwent laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma from 2002 to 2020. The patients were divided into octogenarians and younger patients (age: < 80 years), and their clinical characteristics, perioperative parameters, and postoperative complications were evaluated. The predictors of postoperative complications were evaluated using logistic regression models. Recurrence-free survival, cancer-specific survival, and overall survival were measured using the Kaplan-Meier method. RESULTS: Twelve (17.1%) octogenarians and 40 (18.7%) younger patients had postoperative complications. No significant difference in the incidence of postoperative complications was observed between octogenarians and younger patients (p = 0.14). A high body mass index was a significant risk factor for complications (p = 0.03). The 5-year recurrence-free survival, cancer-specific survival, and overall survival rates for octogenarians and younger patients were 72% and 64% (p = 0.31), 76% and 63% (p = 0.63), and 43% and 63% (p = 0.06), respectively. CONCLUSION: Laparoscopic radical nephroureterectomy can be performed in octogenarians with complication rates similar to those in younger patients. Similarly, the outcomes of laparoscopic radical nephroureterectomy for oncological control do not differ significantly between octogenarians and younger patients. This procedure is safe and effective for selected octogenarians.

Oncological Outcomes of Retroperitoneal Lymph Node Dissection During Retroperitoneal Laparoscopic Radical Nephroureterectomy for Renal Pelvic or Upper Ureteral Tumors: Matched-Pair Analysis.

Objectives: The aim of this study was to investigate the oncological outcomes and recurrence patterns in clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU). Materials and Methods: A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template for RPLND included the renal hilar and para-aortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no-RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses. Results: Compared with the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated 5-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared with the group without RPLND (64.2%) (p = 0.014). The estimated 5-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while no significant difference was observed in the rate of regional LN recurrence. Conclusions: This study suggests that template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves recurrence-free survival by reducing distant recurrences.

Complications and their management following retroperitoneal lymph node dissection in conjunction with retroperitoneal laparoscopic radical nephroureterectomy.

OBJECTIVES: To describe the detailed perioperative complications and their management after retroperitoneal lymph node dissection with retroperitoneal laparoscopic radical nephroureterectomy for patients with upper tract urothelial carcinoma at three institutions. METHODS: Retroperitoneal lymph node dissection was performed on patients with upper tract urothelial carcinoma located at the pelvis and/or upper or middle ureter, and its template included the renal hilar and para-aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side). The lymph nodes and kidneys were removed en bloc. The primary endpoint was postoperative complication rates, and the secondary endpoints were intraoperative findings and chylous leakage management. The associations of retroperitoneal lymph node dissection with postoperative complications were examined using logistic regression with propensity score techniques. RESULTS: Eighty-eight (31%) and 195 (69%) patients underwent and did not undergo retroperitoneal lymph node dissection, respectively. There was no significant difference in postoperative complications and other perioperative findings in the entire cohort, except for prolonged operation time. Retroperitoneal lymph node dissection was not statistically significantly associated with total and serious complications in propensity score analyses. Postoperative chylous leakage could be conservatively managed even though it is common in patients with retroperitoneal lymph node dissection (14/88 (16%)). The incidence of chylous leakage was significantly lower in patients whose lymphatic vessels were meticulously clipped completely during retroperitoneal lymph node dissection (5.3% vs 24%; P = 0.017). CONCLUSION: There was no association between retroperitoneal lymph node dissection with laparoscopic radical nephroureterectomy and postoperative complications. However, chylous leakage is often observed after retroperitoneal lymph node dissection and careful management is highly required. The use of clips during retroperitoneal lymph node dissection is recommended to minimize chylous leakage risk.

[Factors Predicting Difficulty of Morcellation during Holmium Laser Enucleation of the Prostate].

To identify which patients will have difficulty during morcellation in holmium laser enucleation of the prostate (HoLEP), we analyzedthe association of preoperative factors with morcellation efficiency retrospectively. Between March 2015 andMay 2019, 129 patients with benign prostatic hyperplasia (BPH) underwent HoLEP at our institution. Based on the morcellation efficiency (morcellation volume per minute), they were classifiedinto easy (≥3 g/min, n＝81) andd ifficult (＜3 g/min, n＝48) groups. In patients who underwent computed tomography (CT) before the surgery, CT values of the prostatic adenomas were measured. The preoperative parameters were comparedbetween the two groups. Comparedwith the easy group, the morcellation time in the difficult group was significantly longer (median, 11 vs 18.5 min, ＜0.001), though prostate volume was not significantly different (median, 76.3 vs 69.3 ml, p＝0.116). The body mass index (BMI) was significantly lower in the difficult group (median, 23.2 vs 21.9 kg/m2, p＝0.007), andit was positively correlatedwith morcellation efficiency. The difference between the maximum andaverage CT values tended to be lower in the difficult group (median, 43.6 vs 39.2 HU, p＝0.066), andit was positively correlatedwith BMI andmorcellation efficiency. Morcellation appearedto be difficult in BPH patients with low BMI because of the homogeneous hardness of prostatic adenoma.

Perioperative and oncological outcomes of laparoscopic radical cystectomy with intracorporeal versus extracorporeal ileal conduit: A matched-pair comparison in a multicenter cohort in Japan.

OBJECTIVES: To compare the perioperative and oncological outcomes of pure laparoscopic intracorporeal ileal conduit urinary diversion versus extracorporeal ileal conduit urinary diversion after laparoscopic radical cystectomy for bladder cancer in a multicenter cohort in Japan. METHOD: A total of 455 patients who underwent laparoscopic radical cystectomy carried out at 10 institutions were included in this retrospective study. The perioperative data of the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups were compared using the propensity score matching method. The Kaplan-Meier curves were obtained to elucidate time to ureteroenteric stricture, reoperation, recurrence and survival. RESULTS: In total, 72 matched pairs were evaluated for the final analysis. The median follow-up period was 28 and 23 months in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively. The operative time in the intracorporeal ileal conduit urinary diversion group was approximately 1 h longer than that in the extracorporeal ileal conduit urinary diversion group. The early and late postoperative complication rates were similar in both groups, except for the reduced wound-related complication rates in the intracorporeal ileal conduit urinary diversion group. The median days to regular oral food intake were 4 and 5 days in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively (P = 0.014). No significant difference was noted in the occurrence of ureteroenteric strictures and reoperation rate. Furthermore, recurrence-free, cancer-specific, and overall survival rates and recurrence patterns did not significantly differ. CONCLUSIONS: Laparoscopic intracorporeal ileal conduit urinary diversion is a safe, feasible and reproducible procedure with similar postoperative complication rates, ureteroenteric stricture rate and oncological outcomes when compared with extracorporeal ileal conduit urinary diversion, but faster postoperative bowel recovery and decreased wound-related complication rates.

Preoperative hydronephrosis as a predictor of postnephroureterectomy survival in patients with upper tract urothelial carcinoma: a two-center study in Japan.

OBJECTIVE: To evaluate the predictive value of preoperative hydronephrosis for pathological outcome and prognosis in patients with upper tract urothelial carcinoma treated with nephroureterectomy. METHODS: 167 patients with UTUC treated with nephroureterectomy at our two institutions in Japan between 2002 and 2017 were retrospectively analyzed. Preoperative computed tomography scans were evaluated for the presence of ipsilateral hydronephrosis. Preoperative hydronephrosis's associations with pathological outcome and postnephroureterectomy survival were assessed. RESULTS: Ipsilateral hydronephrosis was present in 102 patients (61.1%). Preoperative hydronephrosis was not associated with higher pathological T stage (T3 or greater). Patients with preoperative hydronephrosis compared with patients without preoperative hydronephrosis had significantly worse recurrence-free survival (RFS) (5-year survival, 61.9% and 77.6%, respectively; p = 0.033), disease-specific survival (DSS) (5-year survival, 66.9% and 88.1%, respectively; p = 0.026), and overall survival (OS) (5-year survival, 54.5% and 80.6%, respectively; p = 0.030). A multivariate Cox regression model identified preoperative hydronephrosis and higher clinical T stage (T3 or greater) as an independent predictor of shorter RFS (p = 0.015 and 0.0009, respectively). We segregated the patients into three risk groups based on the number of these two prognostic factors: 0, favorable risk; 1, intermediate risk; 2, poor risk. The favorable-risk group had significantly better RFS (p = 0.0003), DFS (p = 0.0001), and OS (p = 0.0007) than the poor and intermediate-risk groups (RFS (p = 0.0011), DFS (p = 0.0017), and OS (p = 0.0043)). CONCLUSION: The presence of preoperative hydronephrosis was a significant risk factor affecting survival. Our risk classification based on preoperative hydronephrosis and clinical T stage may be helpful for patient counselling and decision-making before nephroureterectomy.

[The Safety of Laparoscopic Radical Cystectomy during Initial Phases in a Japanese Multicenter Cohort].

We evaluated the safety of laparoscopic radical cystectomy (LRC) during initial phases and its learning curve in a Japanese multicenter cohort by studying 436 patients who underwent LRC with no robot assistance at 10 institutions in Japan. We divided the patients into three groups according to cumulative surgical volume at each institution (first 10 cases, 11-30 cases, after 31 cases in each institution), and compared perioperative and pathologic variables among the three groups. The first, second, and third groups included 100, 166, 170 patients, respectively. The preoperative variables were similar in the three groups except for the rate of neoadjuvant chemotherapy. The methods of LRC procedure, such as urinary diversion, the extent of lymph node dissection, and concomitant urethrectomy or nephroureterectomy, were similar in the three groups. Mean operative time was 629, 562 and 531 minutes, respectively, and mean blood loss was 755, 650 and 435 ml, respectively. Both values decreased over time with the institution's experience. There was no significant difference among the three groups in the rate of positive surgical margin, the number of retrieved lymph nodes, and the rate of intra- and postoperative complications. LRC was safely performed during initial phases with an acceptable complication rate and without compromising oncological results, although operative time was longer and blood loss increased.

[A Case of Dedifferentiated Liposarcoma of the Spermatic Cord].

A74-year-old man was referred to the department of general surgery in our hospital because of a painless right scrotal swelling persisting for three months. On physical examination, the patient was found to have an inguinal hernia. The patient underwent laparoscopic transabdominal preperitoneal repair, but no inguinal hernia was detected. The patient was referred to our department for a suspected tumor of the spermatic cord. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a clearbordered and homogeneous mass without fat in the right spermatic cord. The findings from the imaging indicated that the mass was benign, but we suspected a malignant tumor because of the rapid enlargement. We performed a right high orchiectomy with a wide excision. Histopathological diagnosis was dedifferentiated liposarcoma with a myxofibrosarcoma-like pattern. He is alive one year after surgery with no recurrence. When a spermatic cord tumor is detected, we need to keep in mind the possibility of malignancy, because it is difficult to make a diagnosis from imaging alone.

Standardized and Simplified Retroperitoneal Lymph Node Dissection During Retroperitoneal Laparoscopic Radical Nephroureterectomy for Urothelial Carcinoma of the Upper Ureter or Renal Pelvis: En Bloc Resection Technique.

OBJECTIVE: To describe our en bloc technique of retroperitoneal lymph node dissection (RPLND) during retroperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma and evaluate perioperative outcomes. METHODS: From 2002 to 2015, 114 patients with urinary tract urothelial carcinoma located at the pelvis or upper or middle ureter underwent retroperitoneal laparoscopic radical nephroureterectomy at 2 institutions. Performance of RPLND began in February 2009. The template of RPLND included the renal hilar and para-aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side). After incising Gerota fascia longitudinally, the aorta (left side) or inferior vena cava (right side) was exposed, and the lymphatic and surrounding fatty tissue in the template and kidney was dissected in a single monoblock. Preoperative data were compared between the RPLND and the no-RPLND groups using propensity score matching. RESULTS: In total, 32 matched pairs were evaluated. RPLND was successfully accomplished without open conversion in all cases. The operative time in the RPLND group was approximately 100 minutes longer than that in the no-RPLND group, but there was no significant difference in the blood loss volume or complication rate. The pathologic stages were similar in both groups. The mean number of retrieved lymph nodes was 10.7 (range 3-27), and lymph node metastasis was detected in 5 (16%) cases. CONCLUSION: Retroperitoneoscopic en bloc RPLND permits complete and radical removal of the lymphatic tissue contained in the RPLND template. Our en bloc technique is a safe and feasible procedure with comparable blood loss and complication rates.

An original patient-derived xenograft of prostate cancer with cyst formation.

BACKGROUND: The high rate of failure of new agents in oncology clinical trials indicates a weak understanding of the complexity of human cancer. Recent understanding of the mechanisms underlying castration resistance in prostate cancer led to the development of new agents targeting the androgen receptor pathway; however, their effectiveness is limited. Hence, there is a need for experimental systems that are able to better reproduce the biological diversity of prostate cancer in preclinical settings. In this study, we established a unique patient-derived xenograft (PDX) model to identify biomarkers for treatment efficacy and resistance and better understand prostate cancer biology. METHODS: A prostate cancer tissue sample from a Japanese patient was transplanted subcutaneously into male, severe combined immune-deficient (SCID) mice and this PDX mouse model was named KUCaP3. Sequential tumor volume changes were observed before and after castration. Androgen receptor (AR), prostate-specific antigen (PSA), and other molecular markers were examined immunohistochemically. Sequence analysis of AR was also performed to detect mutations. Proteomic analysis of cyst fluid and sera samples of KUCaP3 mice were analyzed by mass spectrometry (MS). RESULTS: KUCaP3 cell line, derived from human tissue, was successfully and serially passaged in vivo with approximately 60% take rate. KUCaP3 exhibited cyst formation, showed androgen-dependent growth initially, and developed castration-resistant growth several months after castration of the mice. Immunohistochemical analysis showed that KUCaP3 was positive for AR, PSA, CK18, and α-methyl acyl-coenzyme A racemase, but negative for CK5/6 and ERG. The AR gene in KUCaP3 cells contained a substitution from CAT (histidine) to TAT (tyrosine) at the nucleotide positions corresponding to codon 875 (H875Y) in the ligand-binding domain. Chemiluminescent immunoassay revealed higher levels of PSA in cystic fluid and the serum of KUCaP3-bearing mice. MS analysis detected 23 proteins of human origin in cystic fluids of KUCaP3. CONCLUSIONS: We developed KUCaP3, an androgen-dependent PDX model with cyst formation. Several proteins including PSA were detected in the cystic fluid and sera of tumor-bearing mice. This original PDX model has the potential to be used as a clinically relevant model to evaluate molecular markers for prostate cancer diagnosis and treatment. Prostate 76:994-1003, 2016. © 2016 Wiley Periodicals, Inc.

[A case of strangulation of the penis with difficult release].

We report a case of penile strangulation by a metal ring. An 81-year-old man visited our hospital with a complaint of penile swelling and urinary retention caused by a ring placed around the penile root to control the patient's sexual desire; the ring had been placed some days prior to presentation. We could not release the penile strangulation by hand or with a ring cutter in the emergency room. We decided to cut the thick metal ring in the operating room under local anesthesia and sedation with a surgical tool used in the orthopedic department. It took approximately 2 hours to cut the ring. The patient had made a satisfactory recovery 7 days postoperatively, and no complications were observed during the postoperative period.

[Perioperative management of two patients with renal malignant tumor involving the vena cava].

Two patients underwent resection of renal malignant tumors involving vena cava. Such tumors occasionally extend to the inferior vena cava with tumor thrombus and invasion to the lymph nodes and adjacent organs. Perioperative management of patients with these tumors is difficult because of the risk of pulmonary embolism and massive bleeding, and requires appropriate cooperation among the surgical team. In case 1, a 56-year-old man, renal cell carcinoma with tumor thrombus had extended into the intrahepatic vena cava. It was resected after isolating the liver from vena cava and incising the cross-clamped inferior vena cava without extracorporeal circulation or blood transfusion. A prosthetic graft replaced the inferior vena cava. In case 2, a 64-year-old woman, renal pelvis cancer adhered to the inferior vena cava and the mesentery with enlarged lymph nodes. It was separated from the inferior vena cava and removed with the ascending colon. The patient received a blood transfusion of approximately 2,000ml. Cardiomyopathy associated with a left ventricular outflow tract pressure gradient of 100mmHg required perioperative management. After surgery, both patients underwent controlled ventilation in the intensive care unit. After recovery, they were discharged without complications. We discuss perioperative management, with regard to the level of the tumor extension and perioperative complications.

Restoration of cyclin D2 has an inhibitory potential on the proliferation of LNCaP cells.

Despite well known oncogenic function of G1-S cell-cycle progression, cyclin D2 (CCND2) is often silenced epigenetically in prostate cancers. Here we show that CCND2 has an inhibitory potential on the proliferation of androgen receptor (AR)-dependent prostate cancer LNCaP cells. Forced expression of CCND2 suppressed the proliferative ability and induced cell death in LNCaP cells in a cdk-independent manner. Knocking down CCND2 restored the proliferation of LNCaP subclones with relatively high CCND2 expression and low proliferative profiles. Immunoprecipitation using deletion mutants of CCND2 indicated that a central domain of CCND2 is required for binding to AR. A deletion mutant lacking the central domain failed to hinder LNCaP cells. Collectively, our results indicated that CCND2 inhibits cell proliferation of AR-dependent prostate cancer through the interaction with AR. Our study suggests that restoration of CCND2 expression potentially prevents the carcinogenesis of prostate cancer, which is mostly AR-dependent in the initial settings.

[A case of interferon-alpha-resistant renal cell carcinoma responding to interleukin-2 therapy].

A 71-year-old woman was admitted with fever up and weight loss. Abdominal computed tomography (CT) revealed right renal tumor 7 cm in diameter and inferior vena caval thrombus and multiple lymph node metastases and lung metastases. Transabdominal right nephrectomy and thrombectomy was performed and pathological examination was renal cell carcinoma (clear cell carcinoma, G3, INFbeta, v (+), pT3b, pN2) with adrenal invasion and lymph node metastases. She received 600 x 10(4) IU/day of interferon alpha (IFN-alpha) intramuscularly 3 times a week for 16 weeks from the 20th post-operative day. The disease showed progression and liver metastases 5 cm in diameter appeared. Then she received 140 x 10(4) JRU/day of IL-2 (div) 5 times a week for 4 weeks. CT showed a complete response on lung metastases and lymph node metastases and marked decrease of liver metastases after the first course of IL-2. After the second course, the liver mass remained 2 cm in diameter and then radiofrequency ablation (RFA) under CT was performed. CT after RFA showed a low density area at the liver tumor without enhancement. About five years after the operation, she is alive without evidence of disease.