68Ga-PSMA ligand PET/CT integrating indocyanine green-guided salvage lymph node dissection for lymph node metastasis after radical prostatectomy.

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml-1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.

[Primary urothelial carcinoma of the prostate: A case report and review of the literature].

OBJECTIVE: To investigate the clinical diagnosis, treatment and prognosis of primary urothelial carcinoma of the prostate. METHODS: We retrospectively analyzed the clinical data on one case of primary urothelial carcinoma of the prostate and reviewed the relevant published literature. RESULTS: The patient, aged 83 years old and diagnosed with primary urothelial carcinoma of the prostate, was treated by neoadjuvant chemotherapy with gemcitabine plus cisplatin preoperatively, injected with 5-fluorouracil into the cutting edge of the tumor intraoperatively, and pathologically confirmed with high-grade invasive primary urothelial carcinoma of the prostate, followed by adjuvant chemotherapy with gemcitabine plus cisplatin. No recurrence or metastasis was observed during 1-year follow-up. CONCLUSIONS: Primary urothelial carcinoma of the prostate is rare and highly malignant. If the tumor is localized, the patient needs to be treated by neoadjuvant chemotherapy preoperatively, injection with anti-tumor drugs into the cutting edge of the tumor intraoperatively, and adjuvant chemotherapy and regular follow-up postoperatively.

A gene study of a family with hidrotic ectodermal dysplasia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and molecular mechanism of hidrotic ectodermal dysplasia (HED).</p><p><b>METHODS</b>A clinical and gene study was performed for five generations (91 people) in the family of one proband with HED. GJB6 gene detection was performed for 7 patients and 3 normal people in this family.</p><p><b>RESULTS</b>Among the 91 people in this family, there were 17 HED patients, who were manifested as having dysplasia of the fingernails and toenails and sparse or absent hair or body hair. The male patients had a greater degree of sparse hair compared with female patients. In the younger generations, damage to the fingernails and toenails was gradually alleviated. There were patients in each generation, the patient's mother or father definitely had this disease. Both males and females developed this disease, and the inheritance pattern was autosomal dominant inheritance. A heterozygous missense mutation, 31G→A, in GJB6 gene was detected in all patients in this family, but this mutation was not detected in family members without the clinical manifestations of HED.</p><p><b>CONCLUSIONS</b>HED is a hereditary disease with autosomal dominant inheritance and has the clinical features of dysplasia of the fingernails and toenails, hyperkeratosis of palms and soles, and sparse or absent hair or body hair. Male patients have a greater degree of sparse hair. In the younger generations, damage to the fingernails and toenails is gradually alleviated. The missense mutation 31G→A in the GJB6 gene may be one of the molecular mechanisms for HED.</p>

[Functional outcomes of transvesical single-site versus extraperitoneal laparoscopic radical prostatectomy for low-risk prostate cancer].

OBJECTIVE: To compare the perioperative data, pathological results and functional outcomes of transvesical single- site laparoscopic radical prostatectomy (TVSSLRP) with those of nerve-sparing extraperitoneal laparoscopic radical prostatectomy (nsELRP) in the treatment of low-risk prostate cancer (PCa). METHODS: Fifty patients with low-risk organ-confined PCa were randomly assigned to two groups of equal number to receive TVSSLRP and nsELRP, respectively. Comparisons were made between the two groups of patients in such demographic and baseline data as age, comorbidity, body mass index (BMI), serum prostate-specific antigen (PSA), prostate volume, bioptic Gleason score, clinical stage, IIEF-5 score, nocturnal penile tumescence (NPT), penile brachial index (PBI), and penile arterial blood flow velocity as well as in such surgery-related parameters as operation duration, blood loss, blood transfusion, intraoperative complications, positive surgical margin, catheterization time, hospital stay, and postoperative Gleason score, pathologic stage, urinal pad use, PSA level, IIEF-5 score, NPT, PBI and PABFV. RESULTS: All the operations were successfully performed. There were no statistically significant differences between the two groups either in the demographic and baseline data or in intraoperative blood loss, blood transfusion rate, complications, and positive surgical margin. No intraoperative complications and positive surgical margins were found in either group. Compared with nsELRP, TVSSLRP achieved a significantly shorter operation duration ([151.46 ± 40.68] min vs [105.92 ± 26.21] min, P <0.05), catheterization time ([13.01 ± 1.64] d vs [11.24 ± 1.17] d, P <0.05), and hospital stay ([15.76 ± 4.65] d vs [12.92 ± 4.29] d, P <0.05). On the first day and at 1, 3 and 6 months after catheter removal, the urinary continence rates in the TVSSLRP and nsELRP groups were 84% vs 52% (P <0.05), 100% vs 84%, 100% vs 96%, and 100% vs 96%, respectively; and at 3, 6 and 12 months after surgery, the erectile potency rates were 48% vs 28% (P <0.05), 64% vs 52%, and 76% vs 68%, respectively, with an IIEF-5 score ≥ 18, all evidently higher in the TVSSLRP than in the nsELRP group. The penile brachial index and arterial blood flow velocity of the two groups of patients exhibited no significant differences before and after surgery, nor did postoperative complications (grade II) between the TVSSLRP and nsELRP groups (32% vs 40%, P >0.05). The Gleason score and pathologic stage were increased after surgery, but with remarkable differences between the two groups (P >0.05). No biochemical recurrence was found in either group during a 12-month follow-up. CONCLUSION: With the advantages of safety and rapid postoperative recovery, both TVSSLRP and nsELRP are feasible for the treatment of low-risk organ-confined PCa, but the former may achieve an earlier recovery of urinary continence and erectile function than the latter.

ERG rearrangement for predicting subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia and lymph node metastasis.

PURPOSE: We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer. EXPERIMENTAL DESIGN: Samples from 523 patients (361 with early prostate cancer and 162 with HGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n = 59) and the other with an ERG rearrangements rate <1.6% (n = 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n = 56 and node-negative, n = 87). All ERG rearrangement FISH data were validated with ERG immunohistochemistry. RESULTS: A total of 56 (of 59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). There were significant differences in ERG rearrangement rates between lymph node-positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6-89.8] and a specificity at 85.1% (95% CI, 75.8-91.8). ERG protein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH. CONCLUSIONS: The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer.

Effects of a combination of oral anti-diabetes drugs with basal insulin therapy on ß-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Oral anti-diabetes drugs plus basal insulin (OAD + insulin) therapy in patients with newly diagnosed type 2 diabetes might improve ß-cell function and result in extended glycaemic remission. This randomised trial compared the effect on ß-cell function and diabetes remission rate between oral drug alone or with addition of basal insulin. METHODS: One hundred and twenty-nine patients, aged 35-50 years, were enrolled between June 2005 and June 2009. For initial correction of hyperglycaemia, patients with fasting plasma glucose ≥9.0 mmol/L and HbA(1c) ≥ 9.0%, were randomly assigned to therapy with oral drugs + insulin or oral drugs alone. Treatment was stopped after normoglycaemia was maintained for 3 months. Patients were then followed-up with diet and physical exercise. Blood glucose, HbA(1c) and insulin were measured prior to treatment and at 1-year follow-up. RESULTS: More patients achieved target glycaemic control in the oral drugs + insulin group [98.3% (58 of 59)] in less time [(10.4 ± 2.5) days] than those in the oral drug group [95.7% (67 of 70) and (12.4 ± 3.4) days]. At 1-year follow-up, more patients maintained target glycaemia without any drugs in the oral drug + insulin group than in the oral drug group [37.9% (22 of 58) vs 20.9% (14 of 67)]. Both treatments improved homeostasis model assessment-ß (HOMA-ß) and homeostasis model assessment-insulin resistance (HOMA-IR) significantly. They had similar effects on insulin resistance [lg(HOMA-IR): (0.50 ± 0.09) vs (0.48 ± 0.09), p = 0.23]. However, oral drugs + insulin could recover ß-cell function much more than OAD alone could [lg(HOMA-ß): (2.17 ± 0.14) vs (2.11 ± 0.13), p = 0.03]. CONCLUSION: In newly diagnosed type 2 diabetes, therapy with oral drugs + insulin has had favourable outcomes on recovery and maintenance of ß-cell function and protracted glycaemic remission compared with treatment with oral drugs alone.

Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models.

Squamous metaplasia (SQM) is a specific phenotype in response to oestrogen in the prostate and oestrogen receptor (ER) α is required to mediate this response. Previous studies utilizing tissue recombination with seminal vesicle (SV) mesenchyme and prostatic ductal tips from wild type and ERαKO mice suggested that both epithelial and stromal ERα are necessary for SQM. However, tissue recombination is conducted in the renal capsule of immune-deficient mice, in which the microenvironment is different from normal prostate microenvironment in the intact mice. Furthermore, whether the requirement of stromal ERα in the SV for developing SQM is the same as in the prostate is unknown. Therefore, there is a clear need to evaluate the respective roles of ERα in prostate epithelial versus stromal compartments in the intact mouse. Here we generated a mouse model that has selectively lost ERα in either stromal (FSP-ERαKO) or epithelial prostate cells (pes-ERαKO) to determine the requirements of ERα for oestrogen-stimulated prostate proliferation and SQM. Our results indicated that FSP-ERαKO prostates develop full and uniform SQM, which suggests that loss of the majority (~65%) of stromal ERα will not influence oestrogen-mediated SQM. In contrast, loss of epithelial ERα inhibits oestrogen-mediated prostate growth and SQM evidenced by decreasing cytokertin 10 positive squamous cell stratification and differentiation, by reduced ERα protein expression in SQM compared to wild type mice ERα, and by the presence of normal proliferative activities in the oestrogen-treated pes-ERαKO prostates. These in vivo results suggest that epithelial ERα is required for oestrogen-mediated proliferative response and could be an appropriate target for preventing aberrant oestrogen signalling in the prostate.

Cryptotanshinone suppresses androgen receptor-mediated growth in androgen dependent and castration resistant prostate cancer cells.

Androgen receptor (AR) is the major therapeutic target for the treatment of prostate cancer (PCa). Anti-androgens to reduce or prevent androgens binding to AR are widely used to suppress AR-mediated PCa growth; however, the androgen depletion therapy is only effective for a short period of time. Here we found a natural product/Chinese herbal medicine cryptotanshinone (CTS), with a structure similar to dihydrotestosterone (DHT), can effectively inhibit the DHT-induced AR transactivation and prostate cancer cell growth. Our results indicated that 0.5 µM CTS effectively suppresses the growth of AR-positive PCa cells, but has little effect on AR negative PC-3 cells and non-malignant prostate epithelial cells. Furthermore, our data indicated that CTS could modulate AR transactivation and suppress the DHT-mediated AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive PCa LNCaP cells and castration resistant CWR22rv1 cells. Importantly, CTS selectively inhibits AR without repressing the activities of other nuclear receptors, including ERα, GR, and PR. The mechanistic studies indicate that CTS functions as an AR inhibitor to suppress androgen/AR-mediated cell growth and PSA expression by blocking AR dimerization and the AR-coregulator complex formation. Furthermore, we showed that CTS effectively inhibits CWR22Rv1 cell growth and expressions of AR target genes in the xenograft animal model. The previously un-described mechanisms of CTS may explain how CTS inhibits the growth of PCa cells and help us to establish new therapeutic concepts for the treatment of PCa.

Single-port laparoscopic radical prostatectomy: initial experience and technical points to reduce its difficulties.

BACKGROUND: Laparoendoscopic single-site surgery (LESS) approaches have been reported for treating various kidney and pelvic procedures, and are feasible and effective in selected patients. In this study, we aimed to present the initial experience and evaluate the efficacy of laparoscopic radical prostatectomy performed through a single incision using a multichannel port. METHODS: Between July 2010 and April 2011, six patients diagnosed with early stage prostate cancer underwent LESS radical prostatectomy (RP) in our institute. A multichannel port was inserted transperitoneally through a 2-cm umbilical incision. Specially articulating and flexible laparoscopic were used. Some technical tricks and points were applied during the operation to overcome the drawbacks and reduce the difficulties of this approach. Two continuous urethrovesical sutures in both sides were performed to complete both lateral aspects of anastomosis. The two ends of the suture threads were fixed by double Lapro-Clips, instead of the difficult knot-tying. RESULTS: Total operative time was (265 ± 43) minutes. Mean blood loss was (230 ± 65) ml. All cases were completed successfully, without conversion to open surgery or adding additional abdomen ports. No patient required a blood transfusion and no intraoperative complications occurred. The Foley catheter was removed at the 14th day (range 12th - 16th) after surgery. At the 12th week of follow-up, all patients had an undetectable prostate-specific antigen level. Two patients used 2 or 1 pad for continence daily; other patients had achieved good continence. CONCLUSION: In selected cases, LESS-RP is feasible and effective; these technic points and the flexible-articulating instruments are helpful to reduce the operation difficulties.

Changes of androgen receptor and insulin-like growth factor-1 in LNCaP prostate cancer cells treated with sex hormones and flutamide.

Changes of androgen receptor (AR) and insulin-like growth factor-1 (IGF-1) were investigated in LNCaP cells treated with 5α-dihydrotestosterone (DHT), estrone and flutamide. Real-time PCR, immunocytochemistry and western blotting were used to detect the expression of AR and IGF-1 in the presence or absence of various kinase inhibitors. Low concentrations of DHT, estrone and flutamide increased the expression of AR and IGF-1, especially estrone, with concentration and time dependence. With DHT and flutamide, there was a significant alteration in AR expression (p<0.001). The results indicated expression of AR and IGF-1 genes to be influenced by DHT, estrone and flutamide in LNCaP cells, regulated by multiple signal pathways.

Endourologic treatments of distal ureteral obstruction in patients with history of pelvic malignancies: efficacy and safety evaluation.

BACKGROUND & OBJECTIVE: Postoperative tissue adherence, scarring and radiotherapy often lead to extrinsic compression and stricture in the distal ureter of the patients who had history of pelvic malignancies. Our aim was to evaluate the efficacy and safety of endourologic techniques in treating this kind of ureteral obstruction. METHODS: From Jan. 1998 to Mar. 2007, 46 patients with obstruction in the distal ureter and had history of pelvic malignancies underwent endoscopic treatments at the Third Affiliated Hospital of Sun Yat-sen University for relief of the obstruction. Perioperative and follow-up data were analyzed. RESULTS: Of the 46 patients, 25 underwent laparoscopic ureterolysis and uretero-neocystostomy, 18 underwent placement of ureter stent under ureteroscope, 3 underwent percutaneous nephrostomy. No severe complication was recorded. The mean operating time was 82.5 min (range, 30-140 min). The mean blood loss was 45.5 ml (range, 5-180 ml). No blood transfusion was needed. The median follow-up time was 18.2 months (range, 3 months to 6.5 years). Three months after operation, B-ultrasonography and intravenous urography (IVU) showed that 39 (84.8%) patients had recovered normal renal function, the other 7 (15.2%) had hydronephrosis relief and renal function improvement. Nuclear renal scanning showed that the mean postoperative glomerular filtration rate (GFR) in the obstructive kidney was higher than the preoperative level (37.6 ml/min vs. 21.3 ml/min, P<0.05). No stricture in the uretero-bladder anastomotic stoma was recorded. CONCLUSION: Endoscopic operation is an effective and feasible option for managing some selected kinds of distal ureteral obstruction caused by postoperative tissue adherence and radiotherapy in the patients with history of pelvic malignancies.

Reduced expression of alpha-tocopherol-associated protein is associated with tumor cell proliferation and the increased risk of prostate cancer recurrence.

AIM: To examine the impact and prognostic significance of alpha-tocopherol associated protein (TAP) expression in a series of prostate cancer patients. METHODS: Tissues from 87 patients underwent radical prostatectomy were examined for TAP expression by immunohistochemistry. The relationships of the staining results, the clinic pathological characteristics and the recurrence times were analyzed. RESULTS: Compared with the adjacent areas of normal and benign glands, immunoreactivity of TAP was reduced in areas of prostate cancer. A lower TAP-positive cell number per mm(2) of the largest cancer area (defined as TAP-PN) was associated with higher clinical stage (r = -0.248, P = 0.0322). Inverse associations were found among the TAP-PN and positive lymph nodes (r = -0.231, P = 0.0325), preoperative prostate-specific antigen (PSA) levels (r = -0.423, P = 0.0043), tumor size (r= -0.315, P= 0.0210) and elevated tumor cell proliferation, which was indicated by the staining of Ki-67 (r = -0.308, P = 0.0026). TAP-PN was a significant predictor of recurrence univariately (P = 0.0006), as well as multivariately, adjusted for known markers including preoperative PSA, clinical stage, Gleason score, surgical margin, extra-prostatic extension, seminal vesicle invasion and lymph node metastasis (P = 0.0012). CONCLUSION: Reduced expression of TAP was associated with the cell proliferation status of prostate cancer, adverse pathological parameters and the increased risk of recurrence.

[Analysis of the causes of postoperative chest or/and abdomen colic in benign prostatic hyperplasia].

OBJECTIVE: To analyze the causes of chest or/and abdomen colic with in 1 week after prostatectomy and transurethral resection of the prostate (TURP). METHODS: Retrospective studies were made on 120 cases of benign prostatic hyperplasia (BPH) with postoperative colic in the chest or/and abdomen from October 2001 to October 2002, 35 (Group A) treated by prostatectomy and the other 85 (Group B) by TURP. RESULTS: In sequence of frequency, the causes of the postoperative chest or/and abdomen colic were bladder spasm, catheter block, acute gastroenteritis, angina and acute myocardial infarction. CONCLUSION: The causes of chest or/and abdomen colic after prostatectomy are multiple. If the causes are timely established and corresponding measures immediately taken, its complications can be minimized.