Pleiotropy of autism-associated chromatin regulators.

Gene ontology analyses of high-confidence autism spectrum disorder (ASD) risk genes highlight chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional work in vivo has additionally implicated tubulin biology and cellular proliferation. As many chromatin regulators, including the ASD risk genes ADNP and CHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ and KMT5B) specifically with respect to tubulin biology. We observe that all five localize to microtubules of the mitotic spindle in vitro in human cells and in vivo in Xenopus. Investigation of CHD2 provides evidence that mutations present in individuals with ASD cause a range of microtubule-related phenotypes, including disrupted localization of the protein at mitotic spindles, cell cycle stalling, DNA damage and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among tubulin-associated proteins, suggesting broader relevance. Together, these results provide additional evidence that the role of tubulin biology and cellular proliferation in ASD warrants further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms.

American Confederation of Urology (CAU) experience in minimally invasive partial nephrectomy.

PURPOSE: To describe the perioperative and oncology outcomes in a series of laparoscopic or robotic partial nephrectomies (PN) for renal tumors treated in diverse institutions of Hispanic America from the beginning of their minimally invasive (MI) PN experience through December 2014. METHODS: Seventeen institutions participated in the CAU generated a MI PN database. We estimated proportions, medians, 95 % confidence intervals, Kaplan-Meier curves, multivariate logistic and Cox regression analyses. Clavien-Dindo classification was used. RESULTS: We evaluated 1501 laparoscopic (98 %) or robotic (2 %) PNs. Median age: 58 years. Median surgical time, warm ischemia and intraoperative bleeding were 150, 20 min and 200 cc. 81 % of the lesions were malignant, with clear cell histology being 65 % of the total. Median maximum tumor diameter is 2.7 cm, positive margin is 8.2 %, and median hospitalization is 3 days. One or more postoperative complication was recorded in 19.8 % of the patients: Clavien 1: 5.6 %; Clavien 2: 8.4 %; Clavien 3A: 1.5 %; Clavien 3B: 3.2 %; Clavien 4A: 1 %; Clavien 4B: 0.1 %; Clavien 5: 0 %. Bleeding was the main cause of a reoperation (5.5 %), conversion to radical nephrectomy (3 %) or open partial nephrectomy (6 %). Transfusion rate is 10 %. In multivariate analysis, RENAL nephrometry score was the only variable associated with complications (OR 1.1; 95 % CI 1.02-1.2; p = 0.02). Nineteen patients presented disease progression or died of disease in a median follow-up of 1.37 years. The 5-year progression or kidney cancer mortality-free rate was 94 % (95 % CI 90, 97). Positive margins (HR 4.98; 95 % CI 1.3-19; p = 0.02) and females (HR 5.6; 95 % CI 1.7-19; p = 0.005) were associated with disease progression or kidney cancer mortality after adjusting for maximum tumor diameter. CONCLUSION: Laparoscopic PN in these centers of Hispanic America seem to have acceptable perioperative complications and short-term oncologic outcomes.

Laparoscopic management of renal tumors with macroscopic level 1 renal vein involvement.

OBJECTIVE: To describe our surgical experience and clinical outcome in laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) with level 1 renal vein tumor thrombus. PATIENTS AND METHODS: 11 patients with RCC level 1 renal vein tumor thrombus were treated by LRN plus thrombectomy. The mean age was 66.8 years (SD ±11.313); the mean body mass index was 24.76 (SD ±5.091). In all cases, the surgical technique was defined by tumor characteristics and the surgeon's preferences. RESULTS: Surgery was technically successful in all 11 patients. A hand-assisted approach was performed in 3 patients, while pure laparoscopy was used in 8. The mean surgical time was 108.3 min (SD ±28.284); the mean estimated blood loss was 108.33 ml (SD ±106.066); the average hospital stay was 2.8 days (SD ±0.707). There was 1 intraoperative complication (splenic laceration) that was managed laparoscopically. Pathologic examination confirmed RCC in all cases. There were no positive surgical margins. With a mean follow-up of 29 months (27-39), 2 patients had a recurrence. CONCLUSION: This report provides further evidence of the technical feasibility, safety and oncologic adequacy of the laparoscopic approach in RCC with level 1 renal vein involvement. A longer follow-up and multi-institutional studies are needed to adequately evaluate its potential oncologic benefit.

Chylous ascites and high-output chylous fistula after extended pelvic lymph node dissection for urological cancer: a rare postoperative complication.

OBJECTIVES: Chylous ascites and high-output chylous fistula are rare complications following abdominal or pelvic surgery. We report a series of five cases that occurred after pelvic lymph node dissection for urological cancer, in addition to their clinical presentation, diagnosis, and treatment. METHODS: The series comprises five patients; four men in whom robotic radical prostatectomy and extended pelvic lymphadenectomy were performed, and one woman with an infiltrating bladder cancer that underwent robotic anterior pelvic exenteration and extended pelvic lymphadenectomy. The first four patients developed chylous ascites, and the female patient a high-output chylous fistula. RESULTS: In all cases, diagnosis of chylous ascites or chylous fistula was confirmed, and they were handled in varied ways, from observation to medical treatment, paracentesis, and surgery, according to their clinical presentation and evolution. We describe a simple treatment algorithm. CONCLUSION: This rare surgical complication requires a grade of suspicion and a defined treatment according to the probability of the medical compromise. Prevention is an important element. This series, according to our knowledge, is the first description in patients undergoing robotic extended pelvic lymphadenectomy.

Laparoscopic resection of isolated fossa recurrence of renal cell carcinoma after open nephrectomy: report of 6 cases and literature review.

OBJECTIVES: Local recurrence after a correct surgical technique and absence of distant metastasis is a rare occurrence after radical nephrectomy. Surgical resection remains the standard management for this pathological setting. Nevertheless controversy persists over surgical approach and adjuvant treatments. METHODS: We report on perioperative outcomes of a small multi-institutional series of patients with fully laparoscopic management of isolated renal fossa recurrence following open radical nephrectomy. RESULTS: All patients underwent full laparoscopic surgery. Mean operative time was 140 minutes (range 75 to 240 minutes). Only one patient had a Clavien Grade IIIa complication. Mean hospital stay was 3 days (range 2 to 4 days). Out of the six patients, 5 had a mean follow-up of 20 months (range 9 to 32 months). Only one of these patients evolved with distant metastasis after surgery. CONCLUSIONS: Laparoscopic resection of local recurrence after open radical nephrectomy is a challenging but reproducible technique. There is still no consensus or an operative protocol for this clinical setting. However, as long as surgery is kept within the possibilities, a laparoscopic approach should be sought.

Vaginal Gartner cysts: clinical report of four cases and a bibliographic review.

OBJECTIVES: To present a series of four cases of Gartner cysts and their clinical presentation. A bibliographic review was performed. METHODS: The series consisted of 4 women, mean age 39, who complained of a bulge at the anterior vaginal wall, associated with a variety of urinary symptoms. RESULTS: Surgical removal was performed in all cases. The pathological studies confirmed the diagnosis of Gartner cyst. There were no recurrences in the long-term follow-up. CONCLUSION: Vaginal wall cysts are rarely found in common urological practice. Gartner cysts arise as a consequence of the Gartner duct (mesonephric remainder) obstruction and they are located in the anterior or lateral wall of the vagina. They may be associated with renal and ureteral anomalies. Differential diagnosis with other vaginal cysts can only be made by histological studies. The correct treatment is the entire removal through a vaginal approach.

Spontaneous retroperitoneal haemorrhage of renal origin (Wunderlich syndrome): analysis of 8 cases.

OBJECTIVES: To analyze the characteristics, etiology and treatment of a series of patients with spontaneous retroperitoneal hemorrhage from renal causes. METHODS: We retrospectively reviewed patients diagnosed of spontaneous retroperitoneal hemorrhage between 2006 and 2011. All patients consulted for back pain and the diagnosis was made by computed tomography (CT) and /or magnetic resonance (MR). All patients were treated surgically. RESULTS: The series includes 8 patients. Six cases had renal mass and associated hematoma and 2 presented only perirenal hematoma. Six patients underwent total nephrectomy, one underwent partial nephrectomy, and one just drainage of the hematoma.The pathological study showed 4 cases of renal angiomyolipoma (one associated with multiple small renal carcinomas), 2 cases of renal carcinoma and 1 case of hemorrhagic renal infarction. CONCLUSION: Renal masses are the main cause of Wunderlich syndrome and CT is the diagnostic procedure of choice. Surgical treatment is preferred in patients with renal mass diagnosed and cases of hemodynamic compromise.

Renal cancer from laparoscopic to robotic: How to proceed.

The benefits laparoscopic surgery brings to the table are well established in the literature. In our environment however, still most of the reconstructive/oncologic procedures are performed as open surgery. This can be explained by the multiple challenges this technique involves, as well as a demanding learning curve. Technology has provided means to improve precision and usefulness of laparoscopy, as well as broaden its use amongst the medical community by shortening its learning curve. Renal tumors have been managed by laparoscopic approach for the past 20 years. During this time, many studies appeared in the literature comparing this procedure with open surgery. In the vast majority, laparoscopic surgery has the upper hand in regards of perioperative events. A number of series are available regarding the feasibility of robotic radical nephrectomy, however there is no literature available that demonstrates better outcome of robotic radical nephrectomy compared to standard laparoscopy. Laparoscopic partial nephrectomy is technically difficult, which has prevented its massive spread through the urologist community, even amongst trained laparoscopists. Current reports are starting to favor robotic partial nephrectomy over standard laparoscopy regarding perioperative outcomes, with similar oncologic results. More studies have to be performed in order to elucidate the importance of NOTES and LESS in the treatment on localized renal cancer, but the use of the robot will lower their learning curve and probably make them attractive in the short term. Even though this technology has brought laparoscopy closer to a greater number of surgeons, physicians should become familiar and proficient in conventional laparoscopic procedures before embarking into robotics.

[Renal cell carcinoma of the collecting ducts of bellini with retroperitoneal recurrence by another histological subtype Of renal tumor]. / Carcinoma renal de los conductos colectores de bellini con recidiva retroperitoneal por otro tipo histológico de tumor renal.

OBJECTIVE: Collecting Duct Carcinoma or Bellini Carcinoma (CDC) is a rare aggressive histological subtype. We present a case of CDC with retroperitoneal recurrence by another histological subtype of renal tumor and review of the literature. METHODS: A 59-year-old man with no relevant clinical history presented gross hematuria. At the time of diagnosis, a computed tomography ( CT) showed a tumor mass occupying the left renal pelvis. Left Laparoscopic radical nephroureterectomy was performed with endoscopic intramural ipsilateral ureter disinsertion. RESULTS: The pathological diagnosis was CDC with negative surgical margins. A CT scan control was performed 10 months later, showed a left retroperitoneal tumor compatible with a local recurrence. We performed a left subcostal laparotomy with complete resection of the mass. Histological diagnosis was large cell carcinoma with components of granular cells and clear cell. CONCLUSIONS: The CDC is a rare subtype of renal cell carcinoma (RCC) and has an aggressive behavior that is associated with poor prognosis. Surgical resection remains the treatment of choice. We present the first reported case of CDC with retroperitoneal recurrence by another histological subtype of renal tumor.

Fistula between external iliac artery and ileal conduit after radical cystectomy: a life-threatening complication.

OBJECTIVE: To present a rare complication of an iliac artery to ileal conduit fistula after radical cystectomy. METHODS: A 74 year-old man with muscle invasive bladder cancer was submitted for robotic radical cystectomy with intracorporeal ileal conduit. Twenty-four days after surgery he was readmitted due to an active bleeding from the ileal conduit. RESULTS: CT-Scan showed an arterial fistula between the external iliac artery and the ileal conduit. The emergency procedure done was an artery ligation, bilateral cutaneous ureterostomy and extra-anatomic femoro-femoral bypass. CONCLUSIONS: A fistula from the external iliac artery to the ileal conduit is a rare and serious complication in the Bricker type urinary diversion, with only 7 cases reported in the international literature.

Basaloid carcinoma of the prostate: an extremely rare tumor.

OBJECTIVE: The basaloid carcinoma of the prostate (BC) is a rare malignant neoplasm arising from the basal cells of prostatic ducts and acini. We report a case and review the literature. METHODS: A 76-year-old man presented with symptoms of lower obstructive uropathy, the IPSS score was 29 and prostate specific antigen (PSA)of 0,924 ng /ml. Transurethral resection of prostate (TURP) was performed in September 2008, histopathological diagnosis was BC. In February 2009 laparoscopic radical prostatectomy was performed. RESULTS: Histopathological examination revealed a BC with adenoid cystic growth pattern, perineural infiltration and focal involvement of the left seminal vesicle. Immunohistochemically, the cells were negative for PSA, stained and were strongly positive for specific monoclonal antibodies anti-cytokeratin 34ßE12, p63 and BCL-2. The patient has 23 months of follow-up, with complete continence and no evidence of tumor recurrence. CONCLUSIONS: The BC is an extremely rare subtype of malignant tumors of the prostate, where immunohistochemistry plays a fundamental role in diagnosis.

Robot assisted partial nephrectomy (Da Vinci) in an angiomyolipoma associated to Wünderlich Syndrome.

OBJECTIVE: To describe a case of renal angiomyolipoma treated by robotic assisted surgery. METHOD AND RESULTS: We report the case of a 26 year old females patient, in the context of third month pregnancy, who was diagnosed of spontaneous self-limited retroperitoneal hemorrhage due to renal angiomyolipoma. The patient was treated conservatively until normal delivery. At the 3rd month postpartum a robot-assisted (Da Vinci S) nephron sparing surgery (partial nephrectomy) was performed. CONCLUSION: Despite being a benign tumor, there are cases in which the renal angiomyolipoma requires surgical treatment. To our knowledge, after a thorough review of the literature, this would be the first reported case of angiomyolipoma treated with conservative surgery with robotic assistance (Da Vinci S-HD).

Laparoscopic vesicovaginal fistula repair.

OBJECTIVES: Vesicovaginal fistulas are uncommon and remain a surgical challenge. Abdominal hysterectomy remains their main cause. We present our experience in laparoscopic repair of vesicovaginal fistula. METHODS: Between January 2006 and January 2008, 8 laparoscopic transvesical procedures for VVF repair were performed at our institution (O'Connor technique). For each case we analyzed demographic and surgical variables as well as the outcome. Surgical technique is also described. RESULTS: Average patient age was 45 years. All patients had past history of hysterectomy and subsequent history of urine leak through vagina, with a mean evolution time of 22 months. The average operative time was 150 minutes and the mean hospital stay 4.7 days. All patients evolved without complications except one who had urinary tract infection (Pseudomonas aeruginosa) that was treated with antibiotics. After a mean follow up of 32 months, there were no recurrences. CONCLUSION: In experienced hands, transvesical transabdominal laparoscopic vesicovaginal fistula repair is a feasible and safe procedure, preserving all the advantages of minimally invasive surgery.

Discontinuous intrabdominal splenogonadal fusion with germ cell tumor. Excision with robotic assistence. Adult case report.

OBJECTIVE: Present the case of a patient with a discontinuous intrabdominal splenogonadal fusion with an associated germ cell tumor. METHODS: A case of a man of 29 years with bilateral cryptorchidism and left intra-abdominal discontinuous splenogonadal fusion associated with seminoma as an accidental finding in the context of a robotic pyeloplasty due to ipsilateral ureteropelvic junction stenosis. RESULTS: The total operative time was 80 minutes (atrophic gonad removal and pyeloplasty by the Anderson-Hynes technique) with an estimated blood loss less than 100 cc. The hospitalization time was less than 36 hrs. The pathology and immunohistochemical report was compatible with intratubular germ cell neoplasia (seminoma). CONCLUSION: The splenogonadal fusion is an uncommon pathology. While a high clinical suspicion may avoid unnecessary orchiectomy in young patients, its association with disorders such as cryptorchidism should make us suspect the possible presence of a concomitant germ cell neoplasia.

Histological changes due to intravesical instillation of mitomycin C.

OBJECTIVE: Transurethral resection (TUR) is highly effective in the local control of superficial bladder cancer. However, the recurrence rate can reach 80% of the cases. Adjuvant intravesical chemotherapy may decrease significantly tumor recurrence. We describe a bladder adverse reaction to mitomycin C as adjuvant therapy for non-invasive bladder cancer METHODS: Three patients with diagnosis of pTa G1 urothelial carcinoma were treated by TUR plus an instillation of 40 mg. of mitomicin C. A month later, the patients were attended for dysuria and hematuria. Cystoscopy and bladder biopsy were performed in all cases. RESULTS: Multiple sessile lesions suspicious of tumor recurrence were found on cystoscopy. The histopathological diagnosis disclosed the existence of severe atypia of the urothelium and stromal changes similar to those observed after radiotherapy CONCLUSIONS: Adjuvant intravesical chemotherapy with mitomycin C may cause local reactions with macroscopic patterns similar to tumoral recurrences.

Bladder hemangioma: case report.

OBJECTIVE: Bladder hemangioma is a benign rare lesion. There are no pathognomonic clinical signs and management is controversial due to the bleeding risk. We report a bladder cavernous hemangioma resolved using bipolar transurethral resection. METHODS: We review the case of a female patient who presented with asymptomatic hematuria. On cystoscopy we discovered a reddish sessile lesion compatible with bladder hemangioma. We describe the diagnostic work up, surgical management and review other therapeutic alternatives for these lesions. RESULTS: Fifty five year old healthy female patient consulting for total painless hematuria. Cystoscopic evaluation revealed a 1 cm diameter sessile reddish elevated lesion near the bladder neck. We performed a transurethral endoscopic resection using the Gyrus Bipolar resectoscope®. Pathologic report concluded cavernous angioma. CONCLUSION: Bladder hemangiomas are benign and rare lesions. Clinical presentation has no pathognomonic signs although gross painless hematuria is the most frequent complain. Management is controversial due to the bleeding risk of this highly vascularized lesion. However, it appears that small lesions could be treated using transurethral resection. Although they have a benign course, follow up is mandatory to detect recurrence or residual disease.

Mixed epithelial and stromal tumor of the kidney (MEST).

OBJECTIVE: To report an unusual case of renal tumor and review the literature. METHODS: We present a 20 years old female with a history of acute right pyelonephritis. The ultrasound study revealed a tumor-like image in the lower pole of the right kidney . The CT-scan showed a mixed solid and cystic mass of 7 cm. in the lower pole of the right kidney. RESULTS: A right laparoscopic partial nephrectomy was performed. The total operative time was 90 minutes, with 24 minutes of warm ischemia. The estimated blood loss was 50 ml. and the length of stay (LOS) 36 hours. The pathology findings confirm a mixed epithelial and stromal tumor (MEST) of the kidney. CONCLUSION: Mixed epithelial and stromal tumor (MEST) of the kidney is a benign and rare condition that doesn't show a clear difference with other renal tumors in image studies. Nephron-sparing surgery with margin study is the standard treatment when is feasible.

Ureteral inverted papilloma: laparoscopic distal ureterectomy and boari flap.

OBJECTIVE: To report a case of ureteral inverted papilloma (IP) with laparoscopic resolution. METHODS: We report the case of a 30-year-old male patient who consulted for asymptomatic hematuria with the radiological finding of a filling defect at the distal right ureter. Ureteroscopy biopsy was not diagnostic, so laparoscopic ureterectomy with a Boari flap technique was performed. The pathology report showed a ureteral inverted papilloma. CONCLUSION: Laparoscopic ureteral replacement by Boari flap is a safe surgical alternative for defects in the distal ureter with the advantages of a minimally invasive procedure.

Laparoscoscopic synchronous bilateral adrenalectomy.

OBJECTIVES: To report our experience in a series of bilateral synchronous laparoscopic adrenalectomies detailing technique and results. METHODS: A total of 242 laparoscopic adrenalectomies were performed in an 8 year period at our institution. Twenty four out of these were bilateral. Of the 24 patients, 22 (92%) were bilateral and synchronous. Mean patient age was 41.4 years (range 17 to 72 years) and male to female ratio was 1:2.1. RESULTS: Mean adrenal size was 5.5 cm (range 2 to 11 cm). In order of frequency, pathological finding was: pheochromocytoma, cushing`s disease, metastatic lesions, hyperaldosteronism, congenital adrenal hyperplasia, myelolipoma and adrenal adenoma. Complete adrenalectomy was performed in 36 cases (82%) while in 8 cases (18%) partial adrenalectomy was preferred. Mean operative time was 78.6 minutes (range 25 to 210 min) being 79.5 min and 77 min for right and left adrenalectomies respectively. Mean operative bleeding was 63 ml (range 0 to 500 ml). Only one patient received blood transfusion. Intraoperative complications occurred in only one patient (2%), a small tear in the renal vein that was successfully controlled by intracorporeal suturing. Mean hospital stay was 3.2 days (range 2 to 5 days). CONCLUSION: We believe that laparoscopic synchronous bilateral adrenalectomy is a feasible, safe and reproducible technique that should be considered of choice for the management of benign bilateral adrenal pathology.

Retroperitoneal laparoscopic lymph node dissection (RPLND) in testicular cancer.

Retroperitoneal Laparoscopic Lymph node Dissection (RPLND) seems to offer similar staging accuracy and long term outcomes to Open RPLND. It is also a reasonable option in terms of morbidity. However, solid laparoscopic skills are necessary to safely perform this surgery. In the following article, we assess indications, access, surgical technique, complications and controversies of the laparoscopic RPLND.