Adjuvant Single-Dose Upper Urinary Tract Instillation of Mitomycin C After Therapeutic Ureteroscopy for Upper Tract Urothelial Carcinoma: A Single-Centre Prospective Non-Randomized Trial.

Purpose: To address the safety and feasibility of adjuvant single-dose upper urinary tract instillation of mitomycin (ASDM) immediately after therapeutic ureteroscopy for upper tract urothelial carcinoma (UTUC) and to compare urothelial (ipsilateral or bladder) recurrence rates in the ASDM group and controls. Materials and Methods: Between April 2015 and August 2018, 52 patients affected by UTUC were treated by endoscopic ablation, of whom 26 were selected for ASDM. Clinical and perioperative data and 30-day complications were recorded. Urothelial recurrence-free survival (URFS) was evaluated with second-look ureteroscopy (URS) and CT scan/URS every 6 months. Results: ASDM was administered through a Single-J (19/25, 76%) or a Double-J (6/25, 24%) in 25/26 (96%) patients. Median follow-up was 18 months (IQR 10-29). The urothelial recurrence rate was 23.5% and 55.5% in the ASDM group and controls, respectively (p = 0.086). Mean URFS was 28.8 months in the ASDM group vs 18.8 months in controls (log-rank p = 0.067). On multivariate Cox regression, ASDM was associated with a 7.7-fold lower risk of urothelial recurrence (HR = 0.13; 95% CI 0.03-0.65; p = 0.01). Clavien grade ≤II complications occurred in 32% (8/25) and 30.7% (8/26) of the ASDM and control group, respectively (p = 0.9). Two Clavien III complications occurred in the ASDM group: bladder hematuria after concomitant transurethral resection of bladder and obstructive kidney failure in a single-kidney patient. Conclusions: ASDM was well tolerated after therapeutic URS. It appears to reduce the risk of urothelial recurrence in patients affected by low-grade UTUC without bladder tumor. Therefore, its use should be evaluated.

Comparison of biopsy devices in upper tract urothelial carcinoma.

INTRODUCTION: A correct characterization of upper tract urothelial carcinoma (UTUC) lesions is fundamental to appropriately select patients suitable for endoscopic management. We analyzed the diagnostic yield of three different biopsy tools for the histology evaluation of the UTUC. Furthermore, the concordance between biopsy grading and final UTUC pathology results at specimen (i.e., after ureterectomy or radical nephroureterectomy-RNU) was evaluated. MATERIALS AND METHODS: Three different devices were evaluated: 3F biopsy forceps, 6F BIGopsy® Backloading biopsy forceps and the 2.2F Nitinol Basket. Data were collected between January 2015 and October 2017 and retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify the variables related to diagnosis. RESULTS: A total of 302 biopsies were taken: lesions could be characterized in 236 (78.2%) specimens by the pathologist. Positive biopsies for UTUC were found in 140 specimens. In 66 biopsies (21.8%), the quality of the tissue sampled was inadequate for a histological characterization; of these, 55 (83.3%) were taken using 3F forceps and 11 (16.7%) using BIGopsy forceps. No inadequate specimen arose using the 2.2F Nitinol Basket. Among 28 patients who underwent distal ureterectomy or RNU, the tumor was upgraded to high grade in 9 (32%), while in 19 (68%) the grading was confirmed. CONCLUSION: In comparison to 3F forceps, the BIGopsy forceps showed to be more accurate in obtaining sufficient specimen for pathologic examination. In papillary lesions, the 2.2F Nitinol basket achieves a final histology characterization in 100% of the cases. For tumor < 2 cm, there is a high concordance between URS biopsy grade and final pathology (distal ureterectomy or RNU).

Diagnosis and kidney-sparing treatments for upper tract urothelial carcinoma: state of the art.

INTRODUCTION: Conservative management of upper tract urothelial cancer (UTUC) is becoming increasingly popular: the key to success is correct selection of patients with low-risk UTUC based on size (≤2 cm), focality (single lesion), stage (< T2), and grade (low grade). Despite the recent growing interest in the conservative approach to UTUC, the diagnostic process is still a challenge, and kidney-sparing surgery (KSS) is traditionally reserved for patients with contraindications to radical nephroureterectomy. In order to explore the "state of the art" in the diagnosis and conservative treatment of UTUC, a systematic review of the literature was performed. EVIDENCE ACQUISITION: A PubMed, Scopus, and Cochrane search for peer-reviewed studies was performed using the keywords "upper tract urothelial carcinoma" OR "UTUC" OR "upper urinary tract" AND "biopsy" OR "diagnosis" OR "endomicroscopy" OR "imaging" AND "URS" OR "ureteroscopy" OR "kidney-sparing surgery" OR "laser ablation" OR "ureterectomy". We considered as relevant comparative prospective studies (randomized, quasi-randomized, no randomized), retrospective studies, meta-analyses, systematic reviews, and case report series written in the English language. Letters to the editor and contributions written in languages other than English were not considered of value for this review. Eligible articles were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. EVIDENCE SYNTHESIS: Two hundred and sixty-three (263) records were identified using the above-mentioned keywords. Overall, 30 studies were considered relevant for the purpose of this systematic review and for the evidence evaluation process during qualitative synthesis. The outcomes evaluated in this review were the current diagnostic methods and the KSS approaches in UTUC. Furthermore, we included in the review the emerging technology for distinguishing between normal tissue, low-grade UTUC, and high-grade UTUC. CONCLUSIONS: Conclusive diagnosis is fundamental to the decision-making process in patients who could benefit from conservative treatment of UTUC. The most relevant diagnostic modalities are computed tomography urography, local urine cytology, and ureteroscopy with acquisition of an adequate biopsy sample for histology. KSS includes the endourological approach and segmental ureterectomy. Promising technology in the endourological management of UTUC helps in providing intraoperative information on UTUC grading and staging, with a high accuracy. Patients treated conservatively have to undergo stringent postoperative follow-up in order to detect and, if necessary, treat any recurrence promptly. Further larger and multicenter studies are needed to confirm these findings.

Correlation Between Confocal Laser Endomicroscopy (Cellvizio®) and Histological Grading of Upper Tract Urothelial Carcinoma: A Step Forward for a Better Selection of Patients Suitable for Conservative Management.

BACKGROUND: Despite the recent growing interest in the conservative management of upper tract urothelial carcinoma (UTUC), the diagnostic process is still a challenge for the risk of tumor undergrading. Real-time confocal laser endomicroscopy (CLE) provides in vivo microscopic images of tissues using a low-energy laser light source. OBJECTIVE: To describe our initial experience with CLE for the real-time characterization of UTUC. DESIGN, SETTING, AND PARTICIPANTS: Fourteen flexible ureteroscopies (f-URS) were performed at our center with CLE for UTUC. Lesions were preoperatively identified at computed tomography-intravenous urography. Cellvizio system was used during f-URS to perform CLE on the targeted lesions. Biopsies were then performed. INTERVENTION: f-URS with CLE. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Surgeon's CLE readings (low-grade/high-grade/carcinoma in situ [CIS]) were documented in the operation notes. A dedicated genitourinary pathologist-blinded to the surgeon reading-examined all specimens. A third person collected prospectively the CLE readings and the histopathological reports. Cohen's Kappa analysis was performed to test interobserver agreement. RESULTS AND LIMITATIONS: The mean diameter of tumors at computed tomography scan was 26mm (range, 5-50mm). In eight patients, CLE allowed to obtain images compatible with low-grade UTUC, in five patients with high-grade UTUC, and in one case with CIS. We found correspondence between the CLE images and the final histopathological results in seven out of seven cases of low-grade UTUC (100%), in five out of six cases of high-grade UTUC (83%), and in one out of one case of CIS (100%). Substantial agreement was found at interobserver agreement (k=0.64) between CLE and histological reading. No complications and/or limitations related to the use of CLE were recorded. CONCLUSIONS: CLE is a promising new technology in providing a reliable real-time histological characterization of UTUC lesions. Ideal targets might be UTUC patients potentially candidates for conservative management. PATIENT SUMMARY: We believe that a conservative treatment for low-grade upper tract urothelial carcinoma is an option that must be considered. The diagnostic process is still lacking of accurate tools. In this study, we find that confocal laser endomicroscopy, using the Cellvizio system, seems to help the clinician to have a real-time histological characterization of upper tract urothelial carcinoma lesions. This could better select patients for a conservative treatment.

Focal cryoablation: a treatment option for unilateral low-risk prostate cancer.

OBJECTIVES: To assess oncological (biochemical and histological recurrence) and functional (urinary and potency) outcomes in patients with unilateral low-risk organ-confined prostate cancer (PCa) treated with focal cryoablation (FC). PATIENTS AND METHODS: From January 2009 to March 2012, patients with localized PCa who refused active surveillance were assigned to a FC protocol. This was a prospective, single-arm cohort study. Inclusion criteria were: unilateral disease, clinical stage T1c to T2a, prostate-specific antigen (PSA) concentration <10 ng/mL, low volume index lesion and Gleason score ≤6 (3+3). Hemi-ablation was carried out using the Precise(TM) cryoablation system (Galil Medical, Inc., Arden Hills, MN, USA). Oncological (PSA values) and functional (International Prostate Symptom Score and International Index of Erectile Function (IIEF)-5 score) outcomes were analysed at 3-, 6- and 12-month follow-up. The primary endpoint for oncological efficacy, no cancer in ipsilateral side, was based on the 12-month mandatory biopsy. RESULTS: A total of 48 consecutive patients with a mean age of 67 years were included. The median (interquartile range) follow-up was 13.2 (7.4-26.5) months. Follow-up prostate biopsies were negative for the treated lobe in 86% of patients. The mean PSA concentration dropped significantly at 3 months (by 55%) but did not correlate well with positive biopsy results. Urinary symptoms were unchanged. A slight decrease in the IIEF-5 score was present at 3 months, but did not differ significantly from baseline at 6-month follow-up. There were 15% grade 1 and 4% grade 2 complications (Clavien classification). CONCLUSIONS: Focal cryoablation is a low-morbidity option in selected patients with low-risk PCa. We showed PSA concentration to be an unreliable marker for monitoring FC and recommend a protocol of mandatory biopsies for follow-up. A multicentre randomized controlled trial is necessary to confirm the low-morbidity and the biopsy-proven PCa cure rates.

'Trifecta' after radical prostatectomy: is there a standard definition?

OBJECTIVES: To determine the extent of variability in the definitions of the 'trifecta' after radical prostatectomy (undetectable PSA, urinary continence and potency) to be found in the literature. To establish a consensus definition of the trifecta in an effort to standardize criteria and reporting. MATERIALS AND METHODS: A systematic review of published articles found in the PubMed database for the period from January 2003 to March 2012 was performed. The search queries included the keywords 'radical prostatectomy,' 'prostatectomy outcome,' and 'trifecta'. RESULTS: A total of 86 publications were identified of which 14 were used for analysis. Eight different definitions of biochemical recurrence were reported, the most common definition being PSA ≥0.2 ng/mL. The definition of potency was the most variable. Ten different definitions of potency were found, with the most common being 'having erections sufficient for intercourse with or without a phosphodiesterase-5 inhibitor'. Nine different definitions of continence were found. The most common definition of continence was 'wearing no pads'. Only six of the 14 articles used validated questionnaires in their outcome measures. CONCLUSIONS: The definitions of trifecta reported in the literature are highly variable. We propose the following consensus definition based on our analysis: (1) PSA >0.2 ng/mL with confirmatory value; (2) attainment of erections sufficient for intercourse with or without oral pharmacological agents; (3) wearing zero pads. This consensus definition should be considered when designing studies and reporting outcomes of radical prostatectomy.

Simplified technique for parastomal hernia repair after radical cystectomy and ileal conduit creation.

OBJECTIVE: To review the results of parastomal hernia repair with a simplified technique of translocation of the stoma with no need for a midline incision. METHODS: A total of 405 radical cystectomies with creation of an ileal conduit were reviewed at our institution. The primary goal of the review was to determine the incidence of parastomal hernias in a large series of cystectomies and their management at our institution. Surgical correction of parastomal hernia was indicated in case of pain, discomfort, risk of bowel obstruction, and/or distortion of the abdominal wall. The simplified technique includes an elliptical incision around the stoma and dissection of the hernia's sac down to the level of the fascia. The sac is incised and the peritoneum is entered. The ileal conduit is thereafter mobilized to guarantee sufficient length. This is crucial to be able to transpose the conduit 5-10 cm superiorly and to obtain a tension-free ileostomy. RESULTS: Sixty-three patients (16%) presented during the follow-up after ileal conduit a palpable defect or bulge adjacent to the stoma. The review highlighted 19 patients (4.69%) who developed a parastomal hernia and underwent surgical repair. Four cases (21%) recurred at a median follow-up of 55 months. Recurrence was not found to be related to gender, age, body mass index, protein level, radiotherapy, adjuvant chemotherapy, or previous abdominal surgery on univariate analysis. Postoperative complications included one wound infection (5.2%) and one stomal necrosis (5.2%). CONCLUSIONS: The technique herein proposed simplifies the management of parastomal hernia repair by avoiding a midline incision, which implies a reduction in surgical trauma with acceptable recurrence and postoperative complication rate.

[Limits of laparoscopic surgery in the treatment of renal tumors]. / Límites de la cirugía laparoscópica en el tratamiento del tumor renal.

Laparoscopic radical nephrectomy is considered to be the technique of choice in the mangement of stage T1 and T2 renal cancer, though increased mastery of this alternative type of surgery has served to expand its indications. In any case, these procedures have a series of limitations which are tied to the intrinsic characteristics of laparoscopic surgery, and which are associated with the patient and tumor characteristics, and the experience of the surgeon. The present study discusses the different indications and establishes the current limits of laparoscopic surgery applied to the management of renal tumors. Its role in cell-reducing therapy in metastatic disease, and the methods available for reducing tumor implantation in the surgical ports are also commented.

Límites de la cirugía laparoscópica en el tratamiento del tumor renal / Limits of laparoscopic surgery in the treatment of renal tumors

Actualmente se considera la nefrectomía radical laparoscópica como la técnica de elección en el tratamiento del cáncer renal en estadios T1 y T2, aunque el dominio de este tipo de alternativa quirúrgica han ido ampliando sus indicaciones. De todas formas existen límites a este tipo de técnicas que van ligadas a la propia idiosincrasia de la laparoscópica; límites que están en relación con las características del paciente, las características del tumor y la experiencia del cirujano. Se discuten las distintas indicaciones y se establecen los límites actuales de la cirugía laparoscópica en el tratamiento del tumor renal, así como su papel en la terapia citoreductora en enfermedad metastásica y los métodos para disminuir el implante tumoral en los puertos de entrada (AU)

Laparoscopic radical nephrectomy is considered to be the technique of choice in the mangement of stage T1 and T2 renal cancer, though increased mastery of this alternative type of surgery has served to expand its indications. In any case, these procedures have a series of limitations which are tied to the intrinsic characteristics of laparoscopic surgery, and which are associated with the patient and tumor characteristics, and the experience of the surgeon. The present study discusses the different indications and establishes the current limits of laparoscopic surgery applied to the management of renal tumors. Its role in cell-reducing therapy in metastatic disease, and the methods available for reducing tumor implantation in the surgical ports are also commented (AU)

A 25-Year Review of Cuba's Screening Program for Early Detection of Hearing Loss.

Introduction Early screening for hearing loss is currently recognized as an international healthcare standard. In Cuba, such a program was initiated in the capital, Havana, in 1983 and scaled up to national coverage in 1991. Objective Review the development of Cuba's national hearing screening program over the last 25 years (organizational structure, efficiency, coverage and impact on health), and the science and technology developed to sustain it. Intervention The program was organized in two steps: Step 1-clinical selection of children at different stages of development with multiple high-risk registers; Step 2-referral to territorial, hospitalbased centers for auditory brainstem evoked response (ABR) testing, diagnostic evaluation, and intervention. Prior to national scaling-up, the efficiency of this multiple targeted screening (MTS) protocol was evaluated in Havana. Technology and equipment were then developed, and personnel were trained to set up the national screening network. In 1996, the multiple auditory steady-state evoked response (MSSR) technique for objective audiogram estimation was introduced using AUDIX equipment, designed and produced in Cuba for this program. A semi-automated version for neonatal screening has been developed more recently. Several studies have been conducted to evaluate the program's efficiency, coverage, yield, and impact on health. Results During the first stage of implementation in Havana, the MTS protocol correctly identified 72.5% of children with congenital and preverbal hearing loss. Subsequent studies of different aspects of the program have shown that: 1) the mean age of hearing loss detection/intervention in one municipality was reduced from 4 years to 10 months; 2) hearing-impaired children who were screened showed improved language and cognitive development compared to those who were not screened; 3) the MSSR technique predicted type and severity of hearing loss more accurately than physiological techniques used previously and was also shown to be an effective screening method (92% to 96% sensitivity, 100% specificity); and 4) program coverage (25-86%), though reasonably high in some regions, is not complete and needs improvement, particularly in the country's remote and rural areas. Conclusions The MTS protocol can be considered a valid option for increasing the yield and effectiveness of a hearing screening program operating with limited resources. The MSSR technique provides valuable data for the diagnosis and treatment of children detected through a screening program and, with improvements, may also be useful as a screening method.

Test accuracy and prognostic validity of multiple auditory steady state responses for targeted hearing screening.

The test accuracy and prognostic validity of Multiple Auditory Steady State Responses (MSSR) and click Auditory Brainstem Responses (cABR) was compared within the context of a targeted screening protocol. A sample of 508 high-risk babies was first screened using cABR and MSSR (500 and 2000 Hz). All children (failed/ pass) were called back at three to four years of age to determine their hearing status (pure-tone audiometry). Although both methods showed an equally good test performance in the first screen (sensitivity: 100% and specificity: 92-95%), the MSSR may have some potential advantage to identify low-frequency hearing loss. Furthermore, the confirmatory audiometry with MSSR predicted the child hearing status more accurately than the cABR. In conclusion, the MSSR can provide valuable information for the diagnosis and management of infants earlier detected by a screening protocol and further developed might be also useful as a screening test.

Aneurisma de arteria mesentérica superior / Aneurysm of the superior mesenteric artery

No disponible

Criptococosis infantil: Presentación de 3 casos

Se describen 3 casos pediátricos de meningoencefalitis por Criptococcus neoformans serotipo A. El diagnóstico se realizó por examen directo del líquido cefalorraquídeo con tinta china. La cefalea, fiebre, fotofobia y signos meníngeos fueron las manifestaciones clínicas predominantes. Aunque se descartó la infección por VIH se demostró compromiso de la inmunidad celular en todos los pacientes. La evolución fue desfavorable en 1 caso, y coincide con un diagnóstico tardío de la enfermedad. El tratamiento con antifúngicos de acción sistémica (anfotericín B y/o fluconazol) fue efectivo en todos los casos.

3 pediatric cases of meningoencephalitis caused by Cryptococcus neoformans serotype A are described. The diagnosis was made by direct examination of the cerebrospinal fluid with India ink. Headache, fever, photophobia and meningeal signs were the predominant clinical manifestations. Although the HIV infection was discarded, cellular immunity compromise was observed in all patients. The evolution was unfavorable in one case and coincided with a late diagnosis of the disease. The treatment with antifungal agents of systemic action (amphotericin B and/or fluconazole) was effective in all cases.