Synergistic roles of p53 and HIF1α in human renal cell carcinoma-cell apoptosis responding to the inhibition of mTOR and MDM2 signaling pathways.

INTRODUCTION: mTOR and MDM2 signaling pathways are frequently deregulated in cancer development, and inhibition of mTOR or MDM2 independently enhances carcinoma-cell apoptosis. However, responses to mTOR and MDM2 antagonists in renal cell carcinoma (RCC) remain unknown. MATERIALS AND METHODS: A498 cells treated with MDM2 antagonist MI-319 and/or mTOR inhibitor rapamycin were employed in the present study. Cell apoptosis and Western blot analysis were performed. RESULTS AND CONCLUSION: We found that the MDM2 inhibitor MI-319 induced RCC cell apoptosis mainly dependent on p53 overexpression, while the mTOR antagonist rapamycin promoted RCC cell apoptosis primarily through upregulation of HIF1α expression. Importantly, strong synergistic effects of MI-319 and rapamycin combinations at relatively low concentrations on RCC cell apoptosis were observed. Depletion of p53 or HIF1α impaired both antagonist-elicited apoptoses to differential extents, corresponding to their expression changes responding to chemical treatments, and double knockdown of p53 and HIF1α remarkably hindered MI-319- or rapamycin-induced apoptosis, suggesting that both p53 and HIF1α are involved in MDM2 or mTOR antagonist-induced apoptosis. Collectively, we propose that concurrent activation of p53 and HIF1α may effectively result in cancer-cell apoptosis, and that combined MDM2 antagonists and mTOR inhibitors may be useful in RCC therapy.

Protein interactions of cortactin in relation to invadopodia formation in metastatic renal clear cell carcinoma.

In the present study, we wanted to examine the predominant factor/s in the initiation of metastasis. We used samples of advanced grades of renal clear cell carcinoma with documented clinical history of vena caval spread as the experimental group. The major rationale for this selection is the fact that renal cell carcinoma metastasize extensively through the inferior vena cava up to the pulmonary bed and often exist as a continuous mass of metastatic tissue. As cortactin plays a significant role in invadopodia formation during initiation of metastasis, in the present study, we tested expression of cortactin and phospho(tyr421)-cortactin in different grades of renal cell clear carcinoma and examined its property to bind to actin. The findings of the present study suggest that the variations of the local physiological milieu are the driving forces for metastasis by enhancing molecular mechanisms for lamellipodia formation. We conclude that localization of cortactin in cancer cells and interaction between actin and its nucleators are crucial for cancer progression.

Disposable circumcision suture device: clinical effect and patient satisfaction.

In our experience patients undergoing circumcision are mostly concerned about pain and penile appearances. We conducted a prospective randomized trial to assess the benefits of a new disposable circumcision suture device (DCSD). A total of 942 patients were equally divided into three groups (conventional circumcision, Shang ring and disposable suture device group). Patients in the DCSD group were anesthetized with compound 5% lidocaine cream, the others with a 2% lidocaine penile block. Operation time, intra-operative blood loss, incision healing time, intra-operative and post-operative pain, the penile appearance and overall satisfaction degree were measured. Operation time and intra-operative blood loss were significantly lower in the Shang ring and suture device groups compared to the conventional group (P < 0.001). Intra-operative pain was less in the suture device group compared with the other two groups (P < 0.001); whereas post-operative pain was higher in the conventional group compared to the other two groups (P < 0.001). Patients in the suture device (80.57%) and Shang ring (73.57%) groups were more satisfied with penile appearances compared with the conventional circumcision group (20.06%, P < 0.05). Patients in suture device group also healed markedly faster than the conventional group (P < 0.01). The overall satisfaction rate was better in the suture device group (78.66%) compared with the conventional (47.13%) and Shang ring (50.00%) groups (P < 0.05). The combination of DCSD and lidocaine cream resulted in shorter operation and incision healing times, reduced intra-operative and post-operative pain and improved patient satisfaction with the cosmetic appearances.

Horseshoe kidney with retrocaval ureter: one case report.

Horseshoe kidney and retrocaval ureter are uncommon congenital anomalies of the genitourinary system that are easily diagnosed by typical imaging features. Both anomalies presenting in one patient is a rare disease characterized by isthmus of horseshoe kidney between the abdominal aorta and inferior vena cava. The clinical diagnosis and treatment of horseshoe kidney with retrocaval ureter remain a challenge. Here, we reported a case of a 44-year-old man with the two anomalies who was preoperatively diagnosed by unenhanced computed tomography scanning immediately after retrograde pyelography. The literatures on such combined anomalies are reviewed and the diagnostic evaluation and surgical management of this rare entity are discussed.

Current status of endoscopic thyroid surgery in China.

The first cases of video-assisted thyroidectomy and scarless endoscopic thyroidectomy were reported in China in 2001 and 2002, respectively. Breast approach endoscopic thyroidectomy (BAET) has become the most popular procedure for treating thyroid disease in China. Chinese doctors did not pioneer this approach, but contributed toward improvement in technical details such as incision selection, creation of a working space, suture exposure, and control of intraoperative bleeding. Relatively large series confirmed that BAET is a safe procedure but has a long learning curve that can be overcome with training. Surgical stress was not significantly increased despite the larger subcutaneous dissection. BAET to treat malignancy is feasible, but larger series and longer follow-up are warranted before its widespread acceptance.

Clinical benefits of scarless endoscopic thyroidectomy: an expert's experience.

BACKGROUND: By comparison with the conventional surgical approach to thyroidectomy, scarless (in the neck) endoscopic thyroidectomy (SET) has a superior cosmetic result but a very long learning curve. The objective of the present study was to compare surgical outcomes of SET performed by an experienced surgeon with the outcomes of conventional thyroidectomy. METHOD: Enrolled in this study were 25 patients who underwent SET and 18 who underwent conventional surgery. Differences in size of tumor, length of incision, duration of operation, volume of blood loss, pathological findings, postoperative pain, complications, and cosmetic result were investigated. RESULTS: The two groups were well matched. The total length of incisions and volume of blood loss of SET were significantly lower than those of conventional surgery. In addition to the superior cosmetic result, postoperative pain was significantly less severe and rates of hypesthesia or paresthesia and discomfort while swallowing were significantly lower in the endoscopy group. CONCLUSIONS: In experienced hands, SET offers more benefits than the conventional approach, including less postoperative pain and discomfort and a better cosmetic outcome.

The minimally invasive effect of breast approach endoscopic thyroidectomy: an expert's experience.

We evaluated the invasiveness of breast approach endoscopic thyroidectomy (BAET) carried out by surgeon very experienced in this procedure. Twenty-four patients who underwent BAET and 19 patients who underwent conventional thyroidectomy were the study population. Postoperative pain was assessed by a visual analog scale (VAS). The values 2, 12, and 24 h after surgery were significantly lower in the BAET group than those in the conventional group. Serum IL-6 and CRP levels were measured by an ELISA preoperatively and at 2, 12, 24 and 48 h after operation. Their values increased significantly after both procedures when compared to preoperative levels with significant differences between the two groups detected at the 24-hour and 48-hour time points. Subjective and objective evidence supported the notion that BAET could become a minimally invasive procedure if the surgeon gained sufficient experience.

Progress in laparoscopic anatomy research: a review of the Chinese literature.

The development of laparoscopic surgery has generated the new field of study, laparoscopic anatomy. This article reviews the reported literature on laparoscopic anatomy and explores how it has evolved along with advances in abdominal surgery. In addition, the principal concerns in current laparoscopic anatomy research are discussed, including: (1) types of special adjacent anatomical structures; and (2) special surgical planes and anatomical landmarks. Understanding of systematic laparoscopic anatomy can provide the junior surgeons a clear procedural approach, and would benefit laparoscopic surgeons in training.

The learning curve for endoscopic thyroidectomy: a single surgeon's experience.

BACKGROUND: Endoscopic thyroidectomy has been known to surgeons for only 20 years. Related studies still are needed to make up for the deficiency of clinical experience. Research on the learning curve for the endoscopic thyroidectomy could be the method for investigating the operation experience. METHODS: This retrospective study investigated 300 consecutive patients who underwent endoscopic thyroidectomy by a single endoscopist during the past 7 years. The study population was equally divided into 10 groups chronologically. Pearson's chi-square test and one-way analysis of variance were used to compare differences in the demographic data, operative time, operation score system, and follow-up data. RESULTS: The mean operative time was 98.07 min. The mean operation score was 6.00, and the rate of conversion to open surgery was 3.7%. There were no differences in demographic data or complications among the 10 groups. Subcutaneous edema occurred in five cases and transient recurrent laryngeal nerve palsy in five cases. There were significant differences in the mean operative time (p < 0.01) and the mean operation score (p < 0.01) among the 10 groups. Comparison of two neighboring groups showed differences in both operative time (p < 0.05) and operation score (p < 0.01) between groups 2 and 3 and in operation score between groups 5 and 6 (p < 0.05). CONCLUSIONS: The first 60 cases constitute the early stage of the learning curve for endoscopic thyroidectomy. The proficiency and stability of the operation reach the advanced level after 150 cases.

[Carcinoma recurrence rates after laparoscopic nephroureterectomy in patients undergoing transurethral incision of the ureteral orifice and open excision of bladder cuff].

OBJECTIVE: To compare the oncologic efficacy of transurethral incision of the ureteral orifice and open excision of bladder cuff in retroperitoneal laparoscopic nephroureterectomy (LNU) for patients with upper tract urothelium carcinoma. METHODS: The hospital records of 86 patients with upper tract urothelium carcinoma who underwent laparoscopic nephroureterectomy were reviewed retrospectively. 53 of the 86 patients, 22 males and 31 females, aged (68.6+/-14.1), underwent transurethral incision of the ureteral orifice (TUIUO), and 33, 14 males and 19 females, aged (72.4+/-15.2), underwent open excision of bladder cuff. Electric cauterization of the ureteral orifice was performed prior to resection. Follow-up was conducted for 28 (3-47) months. RESULTS: In all the specimens in the TUIUO group scar at the ureter orifice caused by electric excision could be seen. Test to check the pressure of distal ureter in 25 specimens proved that the ureters were all sealed. The distal ureter end began to leak at the water pressure of 135 cm in 1 case, at the water pressure of 167 cm in 1 case, and at 175 cm in 2 cases, but no leaking was seen even at 197 cm H2O in the other cases. Recurrence of bladder tumor was seen in 13 of the 53 patients of the TUIUO group and in 8 of the 33 patients of the open excision of bladder cuff group. Local recurrence developed in one case with the tumor at stage pT4N0M0 8 months after operation. CONCLUSION: Electric cauterization of the ureteral orifice prior to resection effectively ensures the leakproofness of the distal ureter end during LNU. As compared with open excision of bladder cuff, TUIUO does not increase the rate of neoplasm recurrence.