Enzymes involved in l-lactate metabolism in humans.

l-lactate formation occurs via the reduction of pyruvate catalyzed by lactate dehydrogenase. l-lactate removal takes place via its oxidation into pyruvate, which may be oxidized or converted into glucose. Pyruvate oxidation involves the cooperative effort of pyruvate dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into glucose. In addition, pyruvate may undergo reversible transamination to alanine by alanine aminotransferase. Enzymes involved in l-lactate metabolism are crucial to diabetes pathophysiology and therapy. Elevated plasma alanine aminotransferase concentration has been associated with insulin resistance. Polymorphisms in the G6PC2 gene have been associated with fasting glucose concentration and insulin secretion. In diabetes patients, pyruvate dehydrogenase is down-regulated and the activity of pyruvate carboxylase is diminished in the pancreatic islets. Inhibitors of fructose 1,6-bisphosphatase are being investigated as potential therapy for type 2 diabetes. In addition, enzymes implicated in l-lactate metabolism have revealed to be important in cancer cell homeostasis. Many human tumors have higher LDH5 levels than normal tissues. The LDHC gene is expressed in a broad range of tumors. The activation of PDH is a potential mediator in the body response that protects against cancer and PDH activation has been observed to reduce glioblastoma growth. The expression of PDK1 may serve as a biomarker of poor prognosis in gastric cancer. Mitochondrial DNA mutations have been detected in a number of human cancers. Genes encoding succinate dehydrogenase have tumor suppressor functions and consequently mutations in these genes may cause a variety of tumors.

Atypical ductal adenocarcinoma of the prostate with endometrioid immunohistological features.

We present the case of a 52-year-old Caucasian male, admitted to our institution for a verumontanum adenocarcinoma, partially resected endoscopically, a month earlier at another urological clinic. The prior pathological examination wasn't able to give diagnosis. The extensive assessment by clinical workup, ultrasound, flexible cystoscopy, CT scan, and MRI revealed a prostatic tumor extending from the verumontanum to the left lobe and seminal vesicle. The patient underwent radical prostatectomy. The pathological examination revealed a ductal like adenocarcinoma, positive on immunohistochemistry for pan cytokeratin (AE1/AE3), CD10, endomysial antibody EMA and progesterone receptors (PR) and negative for prostate specific antibody (PSA), prostatic specific acid phosphatase (PSAP) and androgen receptors (AR). Ductal like adenocarcinoma of the prostate with endometrioid immunohistological features in the absence of prostate markers is an unusual condition.

[Advantages of ilio-inguinal extraction of the kidney after retroperitoneoscopic nephroureterectomy]. / Avantajele extragerii ilio-inghinale a rinichiului în nefroureterectomia retroperitoneoscopica.

INTRODUCTION: The manner to extract the specimen after retro-peritoneoscopic nephroureterectomy varies to different surgical teams. The aim of the surgeon is to extract the specimen with minimum parietal injuries, according with oncologic principles. The objective of our study was to evaluate the ilio-inguinal approach to extract the specimen after retro-peritoneoscopic nephroureterectomy. MATERIAL AND METHOD: Evaluation and follow-up of 71 patients with retroperitoneoscopic nephroureterectomy for urothelial cancer (65 pelvic urothelial carcinoma and 6 urothelial carcinoma of the ureter). Ilio-inguinal incision was used for 68 patients to extract the specimen. RESULTS: The operating time was 110 +/- 47 min. Blood lost 101 +/- 57 ml. Retroperitoneoscopic approach 10 +/- 4 min. Ilio-inguinal approach 25 +/- 10 min. The weight of the specimen was 601 +/- 127g. Tumor dimension was 5.9 +/- 1.9 cm. No conversion to open surgery was made. No late post surgery complications were registered ( follow-up at 2 and 6 months). CONCLUSIONS: The enlarged nephroureterectomy can be performed using retroperitoneoscopic approach and the specimen can be extracted through an incision at iliac fossa. This approach can be used to extract large specimens preserving the esthetic laparoscopic benefit as well as the oncologic salty and reducing the risk of post-operative eventration.

Retro-peritoneoscopic assisted cryoablation for small renal tumors: the first cases treated in Romania.

Nephron-sparing surgery (NSS), has been demonstrated to be a safe and effective alternative to radical nephrectomy for selected cases. Retro-peritoneoscopic cryoablation (RCA), combine the benefits of minimal invasiveness of the laparoscopy with the advantage of preserving renal function of the nephron sparing surgery. The aim of our study was to assess the initial results with RCA of small renal tumors. Since Jan 2007, twelve consecutive patients, with small renal tumors (mean tumor size 3.89 cm) underwent RCA at our institution. The patients were assessed using: clinical exam, lab exam, ultrasound, contrast enhanced CT scan. For cryoablation, we used the Galil Medical SeedNet with 17 Gauge cryoprobes, under combined retro-peritoneoscopic and ultrasound guidance. Protocol follow-up design includes clinical exam, lab exam and contrast enhanced CT scan at 3,6 and 12 months and annually thereafter. Mean surgical time was 145.42 min. and mean blood loss was 179.17 ml. Two patients presented: bleeding at the extraction of the cryoprobes and urinary fistula which healed with surgical treatment. Histological examination of the core biopsy revealed clear cell carcinoma in 8 patients, papillary carcinoma in 3 patients and angiomyolipoma in 1 patient. Cryosurgical ablation of small renal tumors using multiple ultrathin 17 Gauge cryoprobes is a feasible treatment option. Retro-peritoneoscopic approach allows optimal access to the kidney and endoscopic real-time ultrasound control of the freezing process.

Technical difficulties in retro-peritoneoscopic radical nephrectomy. Is tumor location important?

UNLABELLED: Tumor location on the posterior aspect of the kidney or close to the renal hilum could increase the difficulty of the retro-peritoneoscopic radical nephrectomy. The aim of our study was to assess how tumor location influences the difficulty of the retro-peritoneoscopic radical nephrectomy. PATIENTS AND METHOD: We performed a nonrandomized prospective study in 116 patients with localized renal cell carcinoma who underwent RRN, between Jan. 2000 and Jan. 2005. Twenty-nine patients with a tumor located close to the renal hilum or on the posterior aspect of the kidney (Gr.A) were compared with 87 patients with a tumor at a distance from the renal hilum (Gr.B) in terms of operative time, intraoperative blood loss, and difficulty of the dissection. The difficulty of the dissection was subjectively estimated by the main surgeon using a three degree scale (G1-easy, G2-medium, and G3-difficult). All the operations were finalized by retro-peritoneoscopy and G4-very difficult degree--was not recorded. In the Gr. A, the operative time was longer (117.28 min vs. 94.63 min, p < 0.001) and blood loss was higher (291.86 ml vs. 199.54 ml, p < 0.001). The dissection of the renal pedicle was also more difficult in the Gr. A either for artery dissection (G3 27.59% vs. 11.49%, p = 0.0202) or for vein dissection (G3 20.69% vs. 8.05%, p = 0.0321), while peri-fascial dissection was less frequently difficult (G3 10.34% vs. 28.74%, p = 0.0237). Tumor location close to the renal hilum or on the posterior aspect of the kidney increases the difficulty of renal pedicle dissection.

Five years of single-center experience with paired kidney exchange transplantation.

INTRODUCTION: Due to the organ shortage, living donor transplantation has become a method to bridge the gap. Paired kidney exchange program (PKEP) is a viable method especially when there are incompatible related living donors. Even if there are still some unanswered questions, this program is current in some centers, and there appears to be a tendency to extend it in Europe. The aim of our study was to assess our results with PKEP after 5 years. METHODS: Between January 2001 and December 2005, we performed 56 living donor kidney transplantations using this method. We performed 26 kidney exchange procedures: 23 with two pairs, two with three pairs, and one with four pairs. Extensive preoperative work was necessarily to obtain equivalent pairs from the anatomic, functional, and immunological points of view. The same team performed all transplants. The mean recipient age was 35.59 years (range 29 to 44). Mean waiting time for a renal transplant was 33.27 months (range 11 to 87). RESULTS: At a median follow-up of 41 months (range 7 to 59), the rates of acute rejection and graft survival-19.64% and 98.21%-were similar to direct living donation-14.66% and 97.92%, respectively (P = .35 and .88, respectively). CONCLUSION: The paired kidney exchange program is a viable procedure medically and economically, which can be promoted in centers with a low deceased donor transplantation rate and a high number of incompatible related donors.

[Hypospadias surgery--etiology of complications]. / Etiologia complicatiilor în chirurgia hipospadiasului.

INTRODUCTION & OBJECTIVE: Hypospadias surgery carries a hole list of precocious and late complications which may occur even years later after surgery such as a very late fistula or a recurrent chordee. The aim of this article was to investigate the reasons, why a significant number of patients with different types of hypospadias presents the same kind of postoperative complications. MATERIALS AND METHODS: Records of 51 boys who underwent surgery for different types of hypospadias were reviewed. Primary repair was performed in 41 patients. 12 (29.4%) of them had postoperative complications. 10 boys had previously between 1 to 7 repairs. The complications were those mentioned in the literature (fistulas, stenoses, megalo-urethra and relapse of the ventral curvature). The etiology of the complications was evaluated according to the type of hypospadias, the surgical technique used for the initial corrective surgery and postoperative care. RESULTS: The original malformation had been miss-classified in 10% of the cases; technical mistakes occurred in 70% of the cases; complications derived from the complexity of the repair procedure were documented in 10% of the cases, and in 10% of the cases the cause was complex: technical and postoperative care mistakes. CONCLUSIONS: Complications after hypospadias surgery appears due to five main reasons which usually coexist. In order to prevent complications, an accurate classification must be made, the surgical procedure has to be chosen accordingly, the surgical technique must be perfect and the postoperative care adequate.

[Laparoscopic radical cystectomy with enteric urinary diversion. Alternative to open cystectomy?]. / Cistectomia radicala laparoscopica cu derivatie urinara enterala. Alternativa la operatia clasica?

Radical cystectomy is the standard therapy for invasive bladder cancer, with best oncological results compared to any other therapeutic alternative. Even if laparoscopic radical cystectomy (LRC) is a well established surgical procedure, performing the urinary diversion completely intracorporeal, is still a challenge due to technical difficulties and associated complications. The aim of our study is to present the first series of LRC with ureterosigmoidostomy. Since May 2004 were performed 7 LRC (5 males and 2 females) (Gr. A). All cases were T2N0 clinical stage. These patients were compared with a retrospective group of 50 patients who underwent open procedure (Gr. B) in term of: operative time, blood loss, analgesic requirements, and hospital stay. LRC has a longer operative time but with statistically significant lower blood loss, less analgesia, and shorter hospital stay. The resection margins of the surgical specimens were tumor free at pathologic examination. Long-term follow-up is pending. On short-term, the results of laparoscopic radical cystectomy are encouraging. When significant experience in laparoscopic surgery is lacking, surgeons should exercise caution with completely intracorporeal urinary diversion.

EAU guidelines on renal transplantation.

OBJECTIVES: To produce a guidelines text, on behalf of the European Association of Urology, providing insights in the issues surrounding renal transplantation. METHOD: A group of international experts in renal transplantation carried out a non-structured literature review on available medical databases and urological literature. RESULT: A guideline text is presented providing an overview of key issues involved in the patients' management such as assessment of donors, pre-transplant evaluation, techniques, management, post-transplant care, etc. CONCLUSION: The current text represents a consensus statement developed by a group of international experts in renal transplantation.

Ten years of cyclosporine use in renal transplantation: a single-center experience with 479 renal transplants.

INTRODUCTION: From 1983 to 1996 therapy with cyclosporine in association with low-dose azathioprine and prednisone has been used for transplantation immunosuppression. The aim of our study was to present 10 years experience with cyclosporine. MATERIAL AND METHOD: Among 479 renal transplants performed since 1992, 61 were performed with cadaver donor grafts and 58 in pediatric recipients. From 1992 to 1998, the immunosuppressive protocol included CsA, azathioprine, and prednisone. Since 1998, mycophenolate mofetil (MMF) replaced azathioprine. In 2002, tacrolimus and rapamycin were introduced into our protocols. The patients were assessed in terms of serum creatinine, incidence of acute rejection, cyclosporine side effects, and graft and patient survivals. RESULTS: Five-year patient and graft survivals were higher among recipients receiving CsA-MMF-prednisone when compared with CsA-azathioprine-prednisone. The incidence of acute rejection episodes during the first year after transplantation was less frequent among recipients receiving MMF compared to those treated with azathioprine. The overall 5-year survivals for patients was 86.29% and for grafts 74.04%. CONCLUSION: Cyclosporine remains a useful immunosuppressive drug, which represents a major step toward efficient renal transplantation. The availability of multiple effective immunosuppressive agents allows individualized protocols to reduce toxic effects. The advent of new induction regimens offers more opportunities to prolong graft life.

Management of malignant extrinsic compression of the ureter by simultaneous placement of two ipsilateral ureteral stents.

BACKGROUND AND PURPOSE: Extrinsic ureteral obstruction caused by various malignancies often necessitates urinary diversion. The use of single ureteral stents as a form of urinary diversion results in a high failure rate, while the use of two ipsilateral stents has shown promising results. We report our experience using the latter technique. PATIENTS AND METHODS: Between 1996 and 2001, four male and three female patients with a mean age of 65 years (range 37-95 years) who had extrinsic compression of the ureters underwent single stent management to relieve obstruction. Ureteral obstruction was secondary to prostate cancer (N = 3), cervical cancer (2), non-Hodgkin's lymphoma (1), and transitional-cell cancer of the bladder and ureter (1). After failure of such management, two 7F stents or a combination of 8F/6F double-J ureteral stents were placed. The stents were changed every 4 to 6 months. Follow-up included serial renal ultrasound scans and serum creatinine measurements. RESULTS: Ureteral stricture length ranged from 2 to 4 cm. Insertion of two double-J ureteral stents in a single ureter was successful in all cases. During the mean follow-up of 16 months (range 1-38 months), the ureteral stents were tolerated by all patients, without significant discomfort. Marked improvement of hydronephrosis and alleviation of flank pain was noted in all patients. Three patients have died at 1 to 3 months. Renal function improved, with a mean decline in the serum creatinine concentration from 3.2 mg/dL to 1.48 mg/dL in the five patients tested. CONCLUSION: Simultaneous placement of two double-J ureteral stents for the management of ureteral obstruction secondary to a malignancy is a safe and effective technique.

[Preliminary results in treating superficial bladder tumors by the local instillation of Calmette-Guérin bacilli]. / Rezultate preliminare în tratamentul tumorilor vezicale superficiale cu instilatii locale de bacili Calmette-Guérin.

Post-resection complementary immunotherapy was applied to 55 patients with superficial urinary bladder tumours (Ta, TI) with Calmette-Guérin bacilli (Pasteur strain) prepared by the "Cantacuzino" Institute. The treatment consisted initially in scarification and instillation in 19 patients, and in instillation alone inside the urinary bladder in 43 patients, according to Morales, and respectively Brosman protocols. In 7 patients only Morales immunotherapy was applied initially but after recidive and resection they too were treated according to the Brosman protocol. One should note that most of these tumours were of the recurring type, with multiple recidives in the antecedents in 60% of the patients, and that the surgical treatment, as well as instillation of cytostatic drugs had failed. In the present protocol transurethral resection was carried out in 93% of the cases. After immunotherapy the following aspects were noted: in 75.8% of the patients there were no recidives 25 months in the average after the start of the treatment. In the average 13 months elapsed between the start of the treatment and the occurrence of the first recidive, as compared with 7 months in the average for the controls. Most of the recidives in patients with instillations occurred in those in whom the tumour had gone beyond the basal membrane. In 2 patients with infiltrative recidives total cystectomy was carried out. With regard to degree of anaplasia following BCG instillation there was a down-grading in 43% of the cases. There was no fatality ascribable to BCG treatment in our series, and both general and local complications were insignificant considering the therapeutic benefit.

[Endoscopic resection in the treatment of infiltrative bladder tumors. The analysis of a nonselected group of 111 cases]. / Rezectia endoscopica în tratamentul tumorilor vezicale infiltrative. Analiza unui lot neselectionat de 111 cazuri.

A total of 111 nonselected cases are presented, of infiltrative urinary bladder tumours, in which endoscopic resections were performed. In most of the cases (83% of the patients) the tumours were of the transitional carcinoma type, the transurethral intervention having been planned in advance. In 35% of the cases resection was done by necessity, and in 3% of the patients resection was done as an emergency for hemostatic purposes. Haemorrhage was the most frequent of the surgical complications, and was reported in 5 patients. Renal failure was the most frequent of the medical complications. In 50 patients radiation therapy was carried out following surgery. The late results are as follows; 44% survivals at 2 years, 14% survival at 3 years, and 9% survivals at 9 years.