Yushi Zhang

Sorafenib Neoadjuvant Therapy in the Treatment of High Risk Renal Cell Carcinoma

Objective To evaluate the clinical efficacy of sorafenib as preoperative neoadjuvant therapy in patients with high risk renal cell carcinoma (RCC). Materials and Methods Clinical data of 18 patients with high risk RCC who received surgery done successfully after preoperative neoadjuvant therapy with sorafenib in Peking Union Medical College Hospital (PUMCH) from April 2007 to October 2013 have been reviewed and analyzed in this study. Results Among the 18 patients there were 13 male and 5 female, with a median age of 54.6 years. The objective response rate (ORR) of the operation on the selected patients is very high (94.4%), including 4 cases (22.2%) of partial response (PR) and 13 cases (72.2%) of stable disease (SD). After preoperative sorafenib treatment, the average tumor size of the 18 patients decreased from 7.8 cm (ranging from 3.6 to 19.2 cm) to 6.2 cm (ranging from 2.4 to 16.8 cm), and the median value of average tumor CT value decreased from 61HU to 52 HU. Among the 5 patients who had IVC tumor thrombi, the grades of tumor thrombi in 2 patients who were grade II before sorafenib treatment became grade I and grade 0 respectively, 2 patients of grade III both became grade II. Conclusion Preoperative neoadjuvant therapy with sorafenib for high risk RCC patients can significantly decrease primary tumor volume as well as tumor thrombus, which could help the nephron-sparing surgery (NSS) or radical nephrectomy to be done successfully.

Retroperitoneal Laparoscopic Management of Paraganglioma: A Single Institute Experience.

Objectives To explore the feasibility and safety of retroperitoneal laparoscopic resection of paraganglioma (RLPG) in a large study population. Methods In a six-year period, 49 patients with primary retroperitoneal paragangliomas (PG) underwent retroperitoneal laparoscopic surgery in a single center. Medical records were reviewed, and collected the following data, which were clinical characteristics, perioperative data (operative time, estimated blood loss, intraoperative hemodynamic changes, intraoperative and postoperative complications, and open conversions), and follow-up data (recurrence or distant metastases). Results All PGs were removed with negative tumor margin confirmed by postoperative histopathology. The operative time of RLPG was 101.59±31.12 minutes, and the estimated blood loss was 169.78±176.70ml. Intraoperative hypertensive and hypotensive episodes occurred in 25 cases and 27 cases, respectively. Two open conversions occurred. Two intraoperative complications occurred but were successfully managed endoscopically. Postoperative complications were minor and unremarkable. No local recurrence or distant metastasis were observed during the follow-up period. Conclusions Our experience indicates the feasibility and safety of resection of PGs in a relatively large study population.

CLINICAL FEATURES AND RETROPERITONEAL LAPAROSCOPIC RESECTION OF ADRENAL SCHWANNOMA IN 19 PATIENTS

OBJECTIVE To explore the diagnostic and therapeutic principles of the rare adrenal schwannoma. METHODS We objectively analyzed the detailed clinical data of 19 patients with adrenal schwannoma treated in a large comprehensive medical center in China between January 2009 and March 2014, including general information, clinical manifestations, imaging, adrenal-related endocrine tests, treatment, pathology, and follow-up records. RESULTS Patients included 16 females and 3 males ranging from 23 to 66 years of age (mean, 48.3 ± 12.6 years), of whom 15 were discovered incidentally. Four patients reported mild abdominal discomfort. Each patient had one unilateral lesion, ranging in diameter from 4.0 to 8.8 cm (mean, 6.2 ± 1.2 cm). Lesions were hypoechoic in 16 patients and cystic-solid in 3 patients. Computed tomography (CT) scanning revealed soft tissue density, mostly with calcifications and clear boundaries. Average values in normal and enhanced CT were 28.7 ± 7.2 Hounsfield units (HU) and 59.7 ± 5.4 HU, respectively. Indicators of adrenal-related endocrine tests were normal, except that catecholamines levels were slightly low in 2 patients with excessively large lesions. All patients underwent uncomplicated retroperitoneal laparoscopic surgery, with subsequent pathology confirmation of adrenal schwannoma. The patients have been followed for 6 months to 4 years, with no recurrence. CONCLUSION Our results demonstrate that the onset of adrenal schwannoma is always occult, without typical clinical manifestations and adrenal-related endocrine abnormalities, and the pre-operative diagnosis depends primarily on imaging features of hypoechoic calcifications and mild enhancement. Diagnosis can be confirmed by postoperative pathology. Even with large diameter lesions, retroperitoneal laparoscopic surgery is still the preferred approach, with good prognosis.

Comparison of retroperitoneoscopic versus transperitoneoscopic resection of retroperitoneal paraganglioma: a control study of 74 cases at a single institution.

AbstractWe aimed to compare the safety and patient outcomes of retroperitoneal paraganglioma (PG) following the retroperitoneoscopic and transperitoneoscopic approaches based on large samples.Seventy-four patients with retroperitoneal PG undergoing laparoscopic resection from June 2004 to September 2013 were retrospectively included. The patients were divided into the retroperitoneal (n = 40) and transperitoneal (n = 34) groups. Demographic and perioperative data, including the operation time, estimated blood loss, incidence of intraoperative hypertension, bowel recovery day, postoperative hospital stay, and systemic inflammatory response syndrome (SIRS) were recorded.The retroperitoneal group showed a shorter operation time and earlier postoperative exsufflation time compared with the transperitoneal group (84 ± 28.5 minutes vs 115 ± 35.7 minutes and 1.7 ± 0.6 vs 2.3 ± 0.7 day, respectively; both P < 0.001). No significant differences in the baseline data were observed between 2 groups. All patients, except for 1 case of open conversion, underwent laparoscopic surgery. There were no patient deaths. Data analysis demonstrated no significant difference in the surgical blood loss, incidence of surgical blood pressure elevation, postoperative hospital stay, or incidence of SIRS between 2 groups.The operation time for the retroperitoneoscopic resection of retroperitoneal PG is shorter, and gastrointestinal functions improve more quickly compared to the transperitoneoscopic approach. This study may provide a valuable source of clinical information for clinicians in related fields.

Clinical and genetic analysis of tuberous sclerosis complex‑associated renal angiomyolipoma in Chinese pedigrees

Tuberous sclerosis complex-associated renal angiomyolipoma (TSC-RAML) confers a high risk of bleeding and even mortality. However, data on TSC-RAML in Chinese pedigrees is extremely lacking. The present study aimed to investigate its clinical and genetic characteristics by obtaining a detailed medical history from 6 probands and their family members, and reassessing blood tests, computed tomography and renal dynamic imaging examinations that were conducted in the TSC-RAML patients. The TSC1/TSC2 mutation was detected in 2 families. A total of 3 TSC-RAML patients underwent partial nephrectomy due to a high bleeding risk, and the other 2 were treated with everolimus. The remaining 6 TSC-RAML patients received no clinical intervention and only had clinical follow-uzp. It was found that nearly 37% (18/49) were TSC patients, with the mean ± standard deviation diagnostic age being 34.22±17.73 years old in the 6 pedigrees, 61% (11/18) of whom suffered from TSC-RAML. In the 11 TSC-RAML patients, the maximum diameter of the tumor ranged between 1.20 and 32.50 cm (mean ± standard deviation, 11.48±8.40 cm), the unilateral glomerular filtration rate ranged between 27.20 and 60.10 ml/min (mean ± standard deviation, 42.55±9.73 ml/min), the serum creatinine level ranged between 40.00 and 90.00 µmol/l (mean ± standard deviation, 64.84±16.15 µmol/l) and the hemoglobin concentration ranged between 76.00 and 140.00 g/l (mean ± standard deviation, 107.73±21.04 g/l). Pathogenic mutations of TSC1 (c.733C>T) and TSC2 (c.788_789insC) were detected in family B and C, respectively, as well as certain non-pathogenic mutations, with the maximum diameter of TSC-RAML being 0 cm and 10.3 cm in the two patients from family B and 16 cm and 1.2 cm in the two patients from family C. Expression of phosphorylated-mechanistic target of rapamycin was determined in the TSC-RAML tissues by immunohistochemistry. The maximum diameter of the tumor decreased by 4.90 and 5.30 cm, respectively, in the 2 patients treated with everolimus after 3 months. In conclusion, TSC cannot be easily diagnosed due to its variable characteristics. Growth of TSC-RAML may increase the bleeding risk and reduce the level of hemoglobin, but it does not greatly affect renal function. Individual differences in tumor dimensions existed even with the same pathogenic mutation, except for cases of coexistent non-pathogenic mutations. Everolimus treatment appears to be able to significantly reduce the size of TSC-RAML.

Laparoscopic Nephron Sparing Surgery Assisted with Laparoscopic Ultrasonography on Centrally Located Renal Tumor - Single Center Experience

Objective: To investigate the clinical value of laparoscopic nephron sparing surgery (LNSS) assisted with laparoscopic ultrasonography (LUS) on centrally located renal tumors. Materials and Methods: Clinical data of 19 patients who underwent LNSS on centrally located renal tumors assisted with LUS were retrospectively analyzed. LUS was used to confirm the location, size, blood supply, and boundary of renal tumors, and to confirm that the tumor was removed completely with negative margin. Results: The 19 centrally located renal tumors were deep in renal parenchyma without obvious convex. Eleven cases were in the middle of the kidney, 3 cases were in the upper pole, and 5 cases were in the inferior pole. The tumor size was in the range 1.0-3.9 cm, with an average of 2.46 cm. The pathological results were 13 cases of renal clear cell carcinoma, 1 case of reninoma, 1 case of renal cyst, and 3 cases of angioleiomyolipoma. The surgical margins were negative in all 19 cases. Conclusions: LUS has a high clinical value in LNNS on centrally located renal tumors and it helps to determine the location of centrally located tumors and guarantee negative margins.

The Clinical Characteristics of Metanephric Adenoma: A Case Report and Literature Review.

AbstractWe describe the clinical presentation, diagnosis, treatment, and follow-up data of a 39-year-old woman with asymptomatic right kidney tumor, which was later histopathologically diagnosed as metanephric adenoma (MA). Macroscopically, the tumor had integrity tegument with homogeneous and gray cutting surface. Microscopically, the tumor cells were formed in adenoid or papillary pattern and contained psammoma bodies, without distinctive atypia. Immunohistochemistry results showed they were negative for creatine kinase 7, epithelial membrane antigen, and renal cell carcinoma, and positive for AE1/AE3, vimentin, and Wilms Tumor 1. Pathological diagnosis was MA. The 48 months’ follow-up information was available without recurrence.According to this case and literature review, we figured that it is difficult to make a definite diagnosis of MA only by image examination. Nephron-sparing surgery is eligible to treat MA. Long-term active surveillance is necessary because of the uncertainty of the biological behavior and cellular origin of MA.

miR-9-5p, miR-124-3p, and miR-132-3p regulate BCL2L11 in tuberous sclerosis complex angiomyolipoma

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by tumor formation in multiple organs, with over 80% of TSC patients developing angiomyolipomas (TSC-AMLs). However, the molecular events that contribute to TSC-AMLs are not well understood. Recent reports have demonstrated that microRNAs (miRNAs) are critical in TSC cortical tubers. However, little is known about the role of miRNAs in TSC-AMLs. In the current study, we analyzed changes in the miRNA and mRNA profiles in TSC-AMLs and matched normal adjacent tissues. A total of 15 differentially expressed miRNAs and 2664 mRNAs were identified. Using quantitative real-time PCR, we confirmed the results of the miRNA and mRNA profile experiments. Through bioinformatic analysis and luciferase reporter assays, we found that BCL2L11, an apoptotic activator, was the direct target of miR-9-5p, miR-124-3p, and miR-132-3p. Engineered expression of miR-9-5p, miR-124-3p, or miR-132-3p significantly regulated proliferation and apoptosis in Tsc2−/− cells. Manipulated expression of BCL2L11 also led to proliferation and apoptosis alterations in Tsc2−/− cells, in agreement with the effects of the above three miRNAs. In addition, BCL2L11 rescued the proliferation and apoptotic inhibition induced by miR-9-5p, miR-124-3p, and miR-132-3p in Tsc2−/− cells. This study provides supportive evidence that miR-9-5p, miR-124-3p, and miR-132-3p play a role in TSC-AMLs through the regulation of BCL2L11.

Correction: miR-9-5p, miR-124-3p, and miR-132-3p regulate BCL2L11 in tuberous sclerosis complex angiomyolipoma

Following the publication of this article, the authors noticed an error was in Figure 5C. In the miR-124-3p mimics, the same image was used accidentally for the miR-132-3p mimics. This does not affect the results and conclusions of the article.

Genotype-phenotype correlation of patients with tuberous sclerosis complex–associated renal angiomyolipoma: a descriptive study

TSC2 gene mutation was repeatedly reported to be associated with a more severe phenotype in patients with tuberous sclerosis complex (TSC). Our current study aims to further explore whether there is such a correlation in patients with TSC-associated renal angiomyolipoma (TSC-RAML). TSC1/TSC2 gene mutation was screened by high-throughput sequencing in 25 TSC-RAML patients from 2 medical centers. Clinical data were also carefully collected. Linear regression analysis and Student t-test were conducted by IBM SPSS Statistics Version 21.0 to analyze the genotypic-phenotypic relationship. The results indicated a high level of TSC gene mutation (80%; 20/25) in TSC-RAML patients, with higher frequency of TSC2 mutation (68%; 17/25) than TSC1 mutation (12%; 3/25). Seven novel mutation sites were detected in this study. In general, there were no significant correlations between tumor size and age (r = 0.134, P = .522), hemoglobin (r = 0.255, P = .219), and serum creatinine (r = 0.043, P = .839). Patients with larger tumor size have higher risk of bleeding. Specially, it was higher hemoglobin level in patients with TSC1 mutation than ones with TSC2 mutation and without TSC mutation (P < .05). However, no difference was found in either tumor size or serum creatinine by TSC mutation genes (P > .05). Furthermore, no difference was found in tumor size, hemoglobin, and serum creatinine by TSC mutation types (P > .05). In conclusion, TSC-RAML is TSC2 mutation dominant, with the individual differences varying greatly. No definite genotype-phenotype correlation exists in patients with TSC-RAML, and it needs to be further explored.