Laparoscopic approach for xanthogranulomatous pyelonephritis and pyonephrosis.

INTRODUCTION: Xanthogranulomatous pyelonephritis (XGPN) is a rare form of chronic renal inflammation, caused by long-term obstruction of the urinary tract. Pyonephrosis is a severe suppurative complication of acute obstructive pyelonephritis. Although minimally invasive approaches have many advantages, the safe dissection of the kidney may not be always achievable. MATERIALS AND METHODS: We reviewed 27 cases diagnosed with either XGPN or pyonephrosis, who underwent laparoscopic total nephrectomy between October 2016 and March 2022 in our department. All interventions were performed using the Karl Storz 3D laparoscopic system. The surgical approach was standard transperitoneal nephrectomy for the majority of XGPN, while pyonephrosis cases were carried out in a retroperitoneally. All procedures were performed or supervised by the same surgeon. RESULTS: The mean operative time was 269.85 minutes (range 145-360). The mean hemoglobin drop after surgery was 1.41 g/dl (range 0.3-2.3 g/dl). Difficult dissection was encountered in 13 cases (48.14%). Nine out of 13 interventions were carried out in a complete intracorporeal fashion, while conversion to open surgery was needed in 4 cases. Vascular complications involving the major blood vessels comprised of one case of inferior vena cava (IVC) tear. Digestive tract-related complications comprised two fistulas of the descending colon and one peritoneal breach. Multiorgan resection was performed in 6 cases. CONCLUSION: Total nephrectomy in cases of XGPN and pyonephrosis is a challenging procedure. The laparoscopic approach is feasible, as most complications are resolved intracorporeally. However, it may remain reserved for large-volume centers with experienced surgeons.

Ralstonia mannitolilytica in cystic fibrosis: A new predictor of worse outcomes.

BACKGROUND: Patients with Cystic Fibrosis are subject to repeated respiratory tract infections, with recent increasing isolation of unusual pathogens. Ralstonia species have lately been isolated at our institution, an organism historically frequently misidentified as Burkholderia or Pseudomonas. The prevalence of Ralstonia spp. in cystic fibrosis populations has yet to be determined, along with its clinical implications. CASE PRESENTATIONS: Seven patients out of the 301 followed at our cystic fibrosis clinic have had Ralstonia strains identified in their respiratory tract. Most strains identified were multi-drug resistant. After aquisition of Ralstonia spp., the patients' clinical course was characterized by more frequent and more severe respiratory infections along with prolonged hospitalizations, greater decline of lung function, and greater mortality. The mortality rate in this group of patients was 86%. No other factor that could explain such a dramatic evolution was identified upon review of patient data. Some of the strains involved were recognized as clones on Pulse Field Electrophoresis Gel, raising the question of person-to-person transmission. CONCLUSION: New pathogens are identified with the evolution of the microbiota in cystic fibrosis respiratory tracts. In our cohort of patients, acquisition of Ralstonia spp. was associated with dramatic outcomes in terms of disease acceleration and raised mortality rates. It is of critical importance to continue to better define the prevalence and clinical impact of Ralstonia in cystic fibrosis populations.

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.

BACKGROUND: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. METHODS: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. RESULTS: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). CONCLUSION: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.

Pulmonary veno-occlusive disease: a rare cause of pulmonary hypertension in systemic sclerosis. Case presentation and review of the literature .

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension (PAH). Because of the similar clinical picture of dyspnea on exertion and signs of right heart failure, PVOD is difficult to distinguish from idiopathic PAH. However, the distinction is mandatory because PVOD has a worse prognosis and, more importantly, the administration of PAH specific therapy (vasodilators) can precipitate severe acute pulmonary oedema. We present a challenging case of PAH in a patient with systemic sclerosis in whom a marked decrease in functional capacity after the initiation of bosentan therapy led to the diagnosis of PVOD. Management of PVOD patients is challenging and referral for lung transplantation should be done at the moment of diagnosis.

GSTM1, GSTT1 and GSTP1 Genetic Variants in Multiple Urologic Cancers.

INTRODUCTION: Glutathione S-transferases (GSTs) are phase 2 enzymes responsible for catalyzing the biotransformation of a wide variety of electrophilic compounds, having a crucial role in the detoxification of active metabolites of procarcinogens produced by phase 1 reactions, tying them to glutathione and promoting their excretion in the urine. OBJECTIVES: we evaluated GSTM1, GSTT1 and GSTP1 genotypes in patients diagnosed with multiple malignancies, of which at least one was found in the prostate, bladder or kidney. MATERIALS AND METHODS: GSTM1, GSTT1 and GSTP1 genotypes were genetically assessed in 34 patients with multiple urologic cancers and 23 patients with urologic cancer associated with another type of cancer. RESULTS: in the group of patients with multiple urologic cancers, GSTT1 null genotype was found in 26.4% of patients compared to 0% in controls, 82.35 % of patients and 47% of witnesses carried at least one GSTM1 or GSTT1 null genotype, and in the group with different cancers, GSTM1 null genotype was found in 52.1% of patients compared to 4.3% witnesses in the control group; GSTT1 null genotype was found in 34.7% of patients compared to 4.3% of witnesses, atleast one GSTM1 or GSTT1 null genotype was found in 73.9% of patients compared to 8.6% of controls. CONCLUSIONS: GSTT1 null genotype is a risk factor for patients with more primitive urologic malignancies (bladder, prostate and kidney); GSTM1 or GSTT1 null genotype is more frequent in patients with multiple urologic tumors; GSTM1 and GSTT1 null genotypes are risk factors in patients with different types of cancer, with at least one affecting the urinary system.

[Postoperative prognosis of chromophobic renal cell carcinoma: comparative analysis of the multinational CORONA database]. / Die postoperative Prognose des chromophoben Nierenzellkarzinoms : Eine vergleichende Analyse anhand der multinationalen CORONA-Datenbank.

BACKGROUND: The chromophobe subtype represents the third most common histological subtype of renal cell carcinoma (chRCC). Due to the rarity of this subtype only one publication regarding the specific analysis of clinical and histopathological criteria as well as survival analysis of more than 200 patients with chRCC is known to date. MATERIALS AND METHODS: A total of 6,234 RCC patients from 11 centres who were treated by (partial) nephrectomy are contained in the database of this multinational study. Of the patients 259 were diagnosed with chRCC (4.2 %) and thus formed the study group for this retrospective investigation. These subjects were compared to 4,994 patients with a clear cell subtype (80.1 %) with respect to clinical and histopathological criteria. The independent influence of the chromophobe subtype regarding tumor-specific survival and overall survival was determined using analysis by Cox proportional hazards regression models. The median follow-up was 59 months (interquartile range 29-106 months). RESULTS: The chRCC patients were significantly younger (60 vs. 63.2 years, p < 0.001), more often female (50 vs. 41 %, p = 0.005) and showed simultaneous distant metastases to a lesser extent (3.5 vs. 7.1 %, p = 0.023) compared to patients with a clear cell subtype. Despite a comparable median tumor size a ≥ pT3 tumor stage was diagnosed in only 24.7 % of the patients compared to of 30.5 % in patients with a clear cell subtype (p = 0.047). In addition to the clinical criteria of age, sex and distant metastases, the histological variables pTN stage, grade and tumor size showed a significant influence on tumor-specific and overall survival. However, in the multivariable Cox regression analysis no independent effect on tumor-specific mortality (HR 0.88, p = 0.515) and overall mortality (HR 1.00, p = 0.998) due to the histological subtype was found (c-index 0.86 and 0.77, respectively). CONCLUSIONS: Patients with chRCC and clear cell RCC differ significantly concerning the distribution of clinical and histopathological criteria. Patients with chRCC present with less advanced tumors which leads to better tumor-specific survival rates in general; however, this advantage could not be verified after adjustment for the established risk factors.

Multiple malignant tumors.

BACKGROUND: Due to the improvement in diagnosis and therapy for certain malignant tumors, we are now faced with patients who develop in time multiple malignancies. METHODS: We conducted a retrospective analysis of the patients diagnosed with at least two primary cancers that were admitted and treated in Cluj-Napoca Municipal Hospital. The study followed patients for a period of 7.5 years. RESULTS: We included in the present study 217 patients (4.33%) with two or more malignant primary tumors from 5003 cases diagnosed with a primary cancer. The most common sites for multiple malignant tumors were related to the breast, colorectum, urinary bladder, prostate and kidneys. CONCLUSIONS: We should always take into consideration the possibility of synchronous tumors and we have to keep in mind that a successful treatment of cancer might not prevent the onset of another primary mass.

Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma.

PURPOSE: The 7th edition of TNM for renal cell carcinoma introduced a subdivision of pT2 tumors at a 10 cm cutoff. In the present multicenter study the influence of tumor size as well as further clinical and histopathological parameters on cancer specific survival in patients with pT2 tumors was evaluated. MATERIALS AND METHODS: A total of 670 consecutive patients with pT2 tumors (10.4%) of 6,442 surgically treated patients with all tumor stages were pooled (mean followup 71.4 months). Tumors were reclassified according to the current TNM classification, and subdivided in stages pT2a and pT2b. Cancer specific survival was analyzed using the Kaplan-Meier method, and univariable and multivariable analyses were used to assess the influence of several parameters on survival. RESULTS: Tumor size continuously applied and subdivided at 10 cm or alternative cutoffs did not significantly influence cancer specific survival. In addition to N/M stage, Fuhrman grade and collecting system invasion also had an independent influence on survival. Integration of a dichotomous variable subsuming Fuhrman grade and collecting system invasion (grade 3/4 and/or collecting system invasion present vs grade 1/2 and collecting system invasion absent) into multivariate models including established prognostic parameters resulted in improvement of predictive abilities by 11% (HR 2.3, p <0.001) for all pT2 cases and 151% (HR 3.1, p <0.001) for stage pT2N0M0 cases. CONCLUSIONS: Tumor size did not have a significant influence on cancer specific survival in pT2 tumors, neither continuously applied nor based on various cutoff values. To enhance prognostic discrimination, multifactorial staging systems including pathological features should be implemented. The prognostic relevance of the variable subsuming Fuhrman grade and collecting system invasion should be considered for future evaluation.

Vascular anatomical variants in renal surgery: classic and robotic approach.

INTRODUCTION AND OBJECTIVES: Conservative renal surgery is based on the nephron-sparing principle. Renal arterial vascularization is of terminal type and the occlusion of an artery generates the necrosis of the corresponding region. The aim of this research is to analyze the anatomic particularities of the renal vascular system as they are highlighted in the course of standard and robotic surgeries. PATIENTS AND METHODS: Between May 2006 and November 2010 we have performed 35 partial nephrectomies out of which 30 cases (85.7%) were performed by standard surgical approach and the other five (14%) were robot-assisted. In the same interval, we have done 103 pyeloplasties to obstruct the pyeloureteral junction: 65 (63%) were carried through by standard surgical approach, 32 (31%) by laparoscopic approach and six cases (6%) were robot-assisted. RESULTS AND DISCUSSION: In 20 (54.3%) of cases, nine (25.7%) had two renal arteries (both superior and inferior), five (14.2%) had early ramifications of the renal artery outside the renal sinus, four (11.4%) patients showed two renal veins, one patient lacked the prepyelic venous plane, and in one patient we have found duplicate abdominal vena cava. Out of all the pyeloplasty cases, 31 (30%) showed an obstruction of the renal collecting system by crossing with a segmental artery or with a vein. CONCLUSIONS: Efficient renal surgery implies good knowledge of anatomical particularities of the renal vascular. The minimally invasive approach by robotic laparoscopy remains an essential coordinate in renal surgery and allows an efficient preparing of the vascular capital.

Computerized method for nonrigid MR-to-PET breast-image registration.

We have developed and tested a new simple computerized finite element method (FEM) approach to MR-to-PET nonrigid breast-image registration. The method requires five-nine fiducial skin markers (FSMs) visible in MRI and PET that need to be located in the same spots on the breast and two on the flanks during both scans. Patients need to be similarly positioned prone during MRI and PET scans. This is accomplished by means of a low gamma-ray attenuation breast coil replica used as the breast support during the PET scan. We demonstrate that, under such conditions, the observed FSM displacement vectors between MR and PET images, distributed piecewise linearly over the breast volume, produce a deformed FEM mesh that reasonably approximates nonrigid deformation of the breast tissue between the MRI and PET scans. This method, which does not require a biomechanical breast tissue model, is robust and fast. Contrary to other approaches utilizing voxel intensity-based similarity measures or surface matching, our method works for matching MR with pure molecular images (i.e. PET or SPECT only). Our method does not require a good initialization and would not be trapped by local minima during registration process. All processing including FSMs detection and matching, and mesh generation can be fully automated. We tested our method on MR and PET breast images acquired for 15 subjects. The procedure yielded good quality images with an average target registration error below 4mm (i.e. well below PET spatial resolution of 6-7 mm). Based on the results obtained for 15 subjects studied to date, we conclude that this is a very fast and a well-performing method for MR-to-PET breast-image nonrigid registration. Therefore, it is a promising approach in clinical practice. This method can be easily applied to nonrigid registration of MRI or CT of any type of soft-tissue images to their molecular counterparts such as obtained using PET and SPECT.

[Atypical progressive multifocal leukoencephalopathy (PML) in a patient with pulmonary sarcoidosis]. / Leucoencéphalopathie multifocale progressive atypique chez un patient atteint de sarcoïdose médiastinopulmonaire.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of central nervous system due to the JC virus. PML generally occurs in immunocompromised hosts and has a fatal outcome. OBSERVATION: We report a case of an atypical PML in a patient with pulmonary sarcoidosis: MRI showed multifocal and punctate contrast enhancements. The diagnostic was made by brain biopsy. CONCLUSION: The pathophysiology of this association is probably related to the immunodepression induced by sarcoidosis.

[Second recurrence of cardiac myxoma 7 years after the initial operation]. / A doua recidiva a unui mixom cardiac aparuta la 7 ani de la prima operatie.

We report a rare case of a 23-year-old woman in who recurrent multiple cardiac myxomas were resected first time 4 years after the initial operation and second time three years after the second operation. In February 2000, she was diagnosed with right ventricular myxoma. The initial cardiac tumor was successfully resected through a right atrium approach and the tricuspid valve was changed with a biological prosthesis; the patient has been followed-up by ultrasound echocardiography every 6-month after discharge. Four years after, the echocardiography revealed one masse in the left atrium, which was resected using a trans-septal approach. Due to malfunction of the tricuspid prosthesis, this was changed with a biological one. After another three years, the echocardiography revealed once again two masses, this time in the right atrium and left ventricle. The third surgery was performed and all 2 myxomas were successfully resected through a combined right atrial and left ventricle approach. One year after the third operation, she has been doing well without any sign of recurrence of myxoma. A long-term follow-up is mandatory in patients after the resection of a cardiac myxoma.

Infertility in a new 46, XX male with positive SRY confirmed by fluorescence in situ hybridization: a case report.

The 46, XX male syndrome (de la Chapelle syndrome or 46, XX testicular disorder of sex development) is a rare form of sex reversal with complex mechanisms leading to a large spectrum of clinical manifestations ranging from ambiguous genitalia in the newborn to normal male phenotype. Therefore, diagnosis is established either pre- or early postnatal, or in adult life due to male infertility. In some cases, subtle clinical signs during childhood and puberty may be overlooked. A 28-year-old married man presented with azoospermia without erectile dysfunction. Between 9-14 years he was examined for the small testes and under-masculinized external genitalia but the diagnosis was not further clarified. At presentation, hormonal laboratory evaluation revealed hypergonadotropic hypogonadism. Chromosome analysis showed a 46, XX karyotype and translocation of SRY (testis-determining factor) from chromosome Y to chromosome X was identified by fluorescence in situ hybridization (FISH). Despite early subtle clinical signs of abnormal sexual development in this new 46, XX male syndrome, medical investigations were triggered by infertility.

Understanding the genetic causes of inter-patient variability. Clinical relevance with focus on cardiovascular drugs.

There is a large inter-patient variability concerning the response to drug therapy and a great interest for determining the causes of this variability. This review takes into discussion some aspects of cardiovascular drugs metabolism and transport, pointing out the effects of genetic variation. Isoenyzmes belonging to the Cytochrome P450 super family have an important role in cardiovascular drug metabolism, namely CYP 1A2; CYP 3A; CYP 2C19; CYP2C9; CYP 2D6, involved in the oxidative phase and also N-acetyltransferase 2, involved in the conjungative phase of the metabolism. P-glycoprotein is implied in cardiovascular drug transport. Polymorphisms of those enzymes and transport protein result in different phenotypes, that is the case of CYP isoenyzmes with abolished, low or increased activity and in the case of N-acetyltransferase 2, slow, intermediate and rapid acetylator phenotypes. There is hope that, in the future, a more individualized treatment of a certain disease, with minimum adverse effects and a maximum therapeutic effect, will be available, by means of genetic testing.

Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis.

Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Na(v)) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na(v) channels), paranodal (paranodin/Caspr) and juxtaparanodal (K(v) channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Na(v) channels is heterogeneous, with a diffuse immunoreactivity but also few broad Na(v) channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na(v) channels, paranodin/Caspr, K(v) channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Na(v) channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Na(v) channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells.

Myocardial infarction in young patients.

Myocardial infarction (MI) is relatively rare in young patients. Atherosclerosis is responsible for most cases, but in one fifth of reported events other causes of MI are involved. Regarding individual susceptibility, it seems that cigarette smoking is the most common modifiable risk factor; family history and lipid abnormalities can also play an important role. In the absence of obvious risk factors a careful search for other contributing factors (such as vasospasm, vasculitis, cardiac masses or hypercoagulable states) is warranted.

Signet-ring prostatic carcinoma. Case presentation and review of the literature.

The authors present the case of a 71 years old man with the histopathological diagnosis of a signet-ring prostatic carcinoma, examined in usual and special stains as PAS and mucicarmin. The literature, the clinical aspect, the microscopic features, and the pathogenesis concerning this subject are reviewed.