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Introduction: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes., Patients and Methods: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant., Results: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer)., Conclusion: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to compare the outcomes of open simple nephrectomy and laparoscopic simple nephrectomy in patients with xanthogranulomatous pyelonephritis (XGP) in a single-institutional retrospective study and to identify predictive factors of surgical approaches and complications., Materials and Methods: We retrospectively analyzed the data of 67 consecutive patients with a histopathological diagnosis of XGP who underwent either open simple nephrectomy (ON) or laparoscopic simple nephrectomy (LN) from January 2014 to April 2020. The primary endpoint was the evaluation of perioperative outcomes and complications. Secondary endpoints were to define factors influencing the surgical approach and the likelihood of postoperative complications., Results: Overall, 44 out of 67 patients (65.67%) underwent ON, while 23 (34.33%) underwent LN. Patients in the ON group experienced more postoperative pain according to the visual analogic scale (p = 0.032). Moreover, time to deambulation and time to return to full daily activities, assessed according to the 12-Item Short Form Survey physical and mental component summary scores questionnaires, were significantly shorter in the LN group (p = 0.021, p < 0.001, and p < 0.001, respectively). Of note, there were no significant differences in intraoperative and postoperative complication rates among the groups (p = 0.258 and p = 0.317, respectively). No conversion to open surgery was described. Logistic regression analysis demonstrated that urgency (p = 0.025) was the only predictor associated with a higher risk of intraoperative complications. However, no independent factors associated with postoperative complications or with the surgical approach of choice were found., Conclusions: Based on our results, laparoscopic treatment of XGP represents a feasible alternative to ON, resulting in less postoperative pain and faster recovery. In skilled hands, LN should be considered as the treatment of choice for XGP., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Introduction: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette-Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC., Objective: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC., Methods: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT., Results and Limitations: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 -35.8). Median age was 70.4 years (IQR: 62.1 -78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% -60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients., Conclusions: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile., Competing Interests: Daniel A. González-Padilla has received payment for trial collaboration from Combat Medical. Félix Guerrero Ramos is a consultant and speaker for Combat Medical. Wei Shen Tan is a consultant to Combat Medical. Joan Palou Redorta is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. Wei Phin Tan, Ana Plata Bello, Carlos Garcia Alvarez, Cajetan Nzeh, Jose Manuel de la Morena, Ignacio Gonzalez Valcarcel de Torres, Kees Hendricksen, Francisco Javier Díaz Goizueta, Fernandez J. Del Alamo, Francesco Chiancone, Paolo Fedelini, Massimiliano Poggio, Francesco Porpiglia, Victoria C. Gonzalo Rodríguez, Javier Montero Torres, Daniel Wilby, Richard Robinson, Alejandro Sousa-Escandón, Juan León Mata, Jose L. Pontones Moreno, Francisco Delgado Molina, Miguel A. Adriazola Semino, Andrew Townsley Stemberger and Jesús Calleja-Escudero declare no conflicts of interest., (© 2022 – The authors. Published by IOS Press.)

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU)., Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC)., Design Setting and Participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021., Outcome Measurements and Statistical Analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta., Results and Limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta., Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field., Patient Summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not., (© 2022 The Author(s).)

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum-Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.

Background: The gold standard treatment for solitary medium-sized (1-2 cm) renal stones is not defined by recent guidelines, since management modalities including shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) are recommended. Improved ability to predict patient outcomes would aid in patients' counseling and decision-making., Objective: To develop a nomogram predicting treatment failure, based on preoperative clinical variables, to be used in the preplanning setting., Design, Setting, and Participants: We recruited 2605 patients from 14 centers and carried out a multicenter retrospective analysis of 699 SWL, 1290 RIRS, and 616 PN L procedures performed as first-line treatment for 1-2-cm kidney stones. The variables evaluated included age, gender, previous renal surgery, body mass index, stone size, location, stone density, skin-to-stone distance, presence of urinary tract infections (UTIs), and hydronephrosis., Outcome Measurements and Statistical Analysis: Multivariate logistic regression was fitted to predict treatment failure, defined as the presence of residual fragments >4 mm. A nomogram was developed based on the coefficients of the logit function., Results and Limitations: A total of 2431 (93.3%) patients were stone free; 174 (6.7%) treatment failures were recorded and considered the event to be predicted. On univariate analysis, type of procedure, preoperative hydronephrosis, stone density, stone location, and laterality turned out to be statistically significant. Skin-to-stone distance, UTIs, and previous renal surgery were predictors of failure on multivariate analysis. Each variable was given a score based on statistical relevance. The main limitation of the current study is its retrospective nature., Conclusions: This nomogram provides a prediction of treatment failure and need of reintervention for medium-sized kidney stones. External validation is needed to determine its reproducibility and validity., Patient Summary: We developed a preoperative model of treatment outcomes for 1-2-cm kidney stones. Its application may assist urologists to counsel patients with regard to stone management modality., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Spontaneous rupture of kidney may involve collecting system or parenchyma. Parenchymal rupture usually occurs in patients with renal cell carcinoma, angiomyolipoma, renal cysts, arteriovenous malformation or vascular diseases such as periarteritis nodosa. Collecting system rupture is usually a rare complication of obstructive urolithiasis. We describe the unusual cases of spontaneous kidney rupture in patients with acute urinary obstruction., Case Presentation: The case report describes the left parenchymal kidney explosion related to ipsilateral ureteral obstruction caused by a single ureteral stone. The patient reached our emergency department with acute left flank pain and massive haematuria. At the moment of admission, the patient was in stage III hypovolemic shock and had a lower haematocrit (haemoglobin = 4.9 g/dL). Despite blood transfusions, emergency surgical exploration, extrafascial nephrectomy and intensive support care, the patient died twelve hours after surgery., Conclusions: Parenchymal renal rupture can be a life-threatening emergency. Despite its rarity, in the differential diagnosis of acute abdomen, parenchymal renal rupture should always be considered in patients with abdominal pain and an anamnesis or history of urinary stones, pointing out the need of early diagnosis also in benign urological conditions.

Introduction: The aim of this study was to compare laparoscopic and open partial nephrectomy (PN) for renal tumors of high surgical complexity (PADUA score ⩾10)., Methods: We retrospectively evaluated 93 consecutive patients who underwent PN at our department from January 2015 to September 2019. 21 patients underwent open partial nephrectomy (OPN) (Group A) and 72 underwent laparoscopic partial nephrectomy (LPN) (Group B). All OPNs were performed with a retroperitoneal approach, while all LPNs were performed with a transperitoneal approach by a single surgical team. Post-operative complications were classified according to the Clavien-Dindo system., Results: The two groups showed no difference in terms of patients' demographics as well as tumor characteristics in all variables. Group A was found to be similar to group B in terms of operation time ( p  = 0.781), conversion to radical nephrectomy ( p  = 0.3485), and positive surgical margins ( p  = 0.338) while estimated blood loss ( p  = 0.0205), intra-operative ( p  = 0.0104), and post-operative ( p  = 0.0081) transfusion rates, drainage time ( p  = 0.0012), pain score at post-operative day 1 (<0.0001) were significantly lower in Group B. The rate of enucleation and enucleoresection/polar resection was similar ( p  = 0.1821) among the groups. Logistic regression analysis indicated that preoperative factors were not independently associated with the surgical approach. There was a statistically significant difference in complication rate (<0.0001) between the two groups even if no significant difference in terms of grade ⩾3 post-operative complications ( p  = 0.3382) was detected., Discussion: LPN represents a feasible and safe approach for high complex renal tumors if performed in highly experienced laparoscopic centers. This procedure offers good intraoperative outcomes and a low rate of post-operative complications.

The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb <12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.

Background: Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes., Methods: Patients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B., Results: A total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis., Conclusions: Our findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ferro, de Cobelli, Musi, Lucarelli, Terracciano, Pacella, Muto, Porreca, Busetto, Del Giudice, Soria, Gontero, Cantiello, Damiano, Crocerossa, Farhan, Autorino, Vartolomei, Muto, Marchioni, Mari, Scafuri, Minervini, Longo, Chiancone, Perdona, De Placido, Verde, Catellani, Luzzago, Mistretta, Ditonno, Caputo, Battaglia, Zamboni, Antonelli, Greco, Russo, Hurle, Crisan, Manfredi, Porpiglia, Di Lorenzo, Crocetto and Buonerba.)

Aim: To investigate the prognostic role of neutrophil percentage-to-albumin ratio (NPAR) in muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC)., Patients & Methods: 213 patients were included., Inclusion Criteria: Nonmetastatic, MIBC (cT2-T4aN0M0), at least three cycles of NAC, undergone RC and with blood count within 30 days before NAC., Results: Five-years overall survival (OS) with NPAR >18 was 34.06% (95% CI: 18.3-50.5) and 65.37% (95% CI: 52.4-75.6) with NPAR <18. Five years cancer-specific survival (CSS) with NPAR >18 was 42.9% (95% CI: 23.9-60.7) and 74.5% (95% CI: 62.6-83.1) with NPAR <18 (p < 0.001). In multivariable analysis, NPAR increased OS of 1.3 points and CSS of 4.37 points., Conclusion: High NPAR prior to NAC seems to be a strong predictor of OS and CSS in MIBC patients treated with NAC and RC., Competing Interests: Financial & competing interests disclosure This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI, project number PN-III-P1-1.1-PD-2019-0085 within PNCDI III. Theauthors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 Matteo Ferro.)

Background: The aim of this study was to compare four renal access techniques in percutaneous nephrolithotomy (PCNL)., Methods: A total of 437 patients who underwent PCNL at our center from January 2015 to December 2019 were included in the analysis. Telescopic metallic coaxial dilation (TMD) was used in 146 patients, single step balloon dilation (BD) in 98 patients, one-shot dilation with 30F Amplatz (OS 30F) in 106 patients, and one-shot dilation with 16F Amplatz (OS 16F) in 87 patients. Primary endpoints were perioperative outcomes and complications of the procedures., Results: Similar baseline characteristics were observed in the four groups. Fluoroscopy time was significantly shorter in OS 30F and OS 16F groups (P<0.0001). The drop in hemoglobin level was not significantly different between TMD and BD groups, but it was significantly lower in OS 16F group versus the OS 30F group and lower in OS 30F group versus the BD Group (P<0.0001). Despite this, the rate of blood transfusion was similar across groups (P=0.837). Moreover, a smaller tract was associated with reduced postoperative morbidity including time to nephrostomy removal (P=0.001), hospital stay (P<0.0001), VAS scale (P<0.0001). There were no significant differences in postoperative complications (P=0.683), and Clavien-Dindo grade ≥3 complication rates (P=0.486) among the groups. Stone-free rates and number of auxiliary procedures required to achieve stone-free status were also similar among all groups (P=0.964 and 0.988, respectively). Multinomial logistic regression analysis showed that BMI (P=0.002), stone size (P=0.002) and previous PCNL (P=0.038) were predictive factors associated with the choice of OS 16 approach., Conclusions: Different dilation methods are equally effective and safe to use in a PCNL procedure for kidney stone treatment, allowing similar stone free rates and risk of complications. The OS dilation techniques seem to allow a shorter X-ray exposure time, which might be beneficial for both patients and operators. The use of a 16 F dilator can reduce the postoperative morbidity. Risk of sepsis should be always kept in mind.

Background: Primary malignant melanoma (PMM) of the bladder represents a very rare clinic-pathologic entity. Given the rarity of the disease, the best treatment option is not well recognized., Case Presentation: We describe a case of neoplasm of the bladder in a 74 years-old Caucasian man presenting with massive hematuria. Based on clinical, instrumental and histological findings a diagnosis of PMM was made. The patient underwent trans urethral resection of bladder tumor plus intravesical Bacillus Calmette-Guérin., Conclusions: To make a correct diagnosis, clinical history, endoscopic evaluation, histopathological examination and immunohistochemistry, are necessary. Multidisciplinary evaluation is required to discriminate primary from metastatic malignant melanoma.

Introduction: The aim of this study was to evaluate the role of TAP block in improvement of anesthesiological management and perioperative surgical outcomes of robot-assisted laparoscopic radical prostatectomy (RALP)., Methods: We consecutive enrolled 93 patients with prostate cancer whose underwent RALP at our department from January 2019 to December 2019. Group A included 45 patients who received bilateral TAP block, and Group B included 48 patients who did not received TAP block. TAP blocks were always performed by a single anesthesia team. An elastomeric pump device was used in all patients for post-operative pain management. TAP block was performed according to Rafi's technique, with Ropivacaine 0.375% and dexamethasone 4 mg. Mean values with standard deviations (±SD) were computed and reported for all items. Statistical significance was achieved if p -value was ⩽0.05 (two-sides)., Results: The two groups showed no difference in the most important demographics and baseline characteristics ( p  > 0.05). Group A showed a significant longer time of anaesthesia. Moreover, Ketorolac doses (started dose plus continuous post-operative infusion via elastomeric pump) used in Group A were significantly lower than Group B. Despite this, Group B showed statistical significant higher value of NRS PACU and at 12, 24, 48, 72 h than Group A but not at 96 h. Rescue analgesic medication use was significantly higher in the Group B than Group A. Moreover, patency of the intestinal tract and time to ambulation was significantly lower in the Group A., Discussion: The use of TAP block during a RALP is a safe procedure that can be applied more appropriately to achieve better pain control. A multimodal protocol that includes locoregional anesthesia, reduction of intra and postoperative use of strong opiates, correct placing of the patient and the use of low pneumoperitoneum pressures should be implemented in order to reach a faster and better post-operative full recovery of patients whose underwent RALP.

Introduction: Over the years, the robotic surgery is gaining increasing importance in the treatment of bladder cancer. Some doubts remain about the oncological safety of robotic approach and alerts have been raised about the occurrence of atypical recurrences, including peritoneal carcinomatosis and port-site metastasis., Case Presentation: The patient referred to our Emergency Department because of acute confusional state probably due to severe anemia and sepsis. A left nephroureterectomy, left hemicolectomy with end colostomy and the surgical excision of the huge mass was performed through a xipho-pubic incision associated to another left peri-stomal incision. The histological specimen analysis showed a high-grade sarcoma, not otherwise specified (sarcoma, NOS-type), measuring 29 cm × 8 cm × 5 cm in diameters. The left kidney and ureter were not infiltrated by the neoplasm while serosa membranes and muscular layers of left colon were infiltrated by the mass. The patient died because of a cardiac arrest 4 days after surgery., Discussion: RARC is a safe and feasible alternative to open radical cystectomy (ORC) with satisfactory operative time, little blood loss, and low transfusion rates. Despite this, RARC is associated with a low, but not neglectable, risk of atypical metastases like peritoneal implants and port-site metastasis. Although a small amount (7%) of RARC were performed in non-urothelial variants of bladder cancer, the sarcomatoid one can be related to a greater risk of atypical recurrence and special precaution should be taken to reduce potential causes of tumor seeding.

Objectives : To evaluate the impact of pre- and post-treatment systemic inflammatory markers on the response to Hyperthermic IntraVEsical Chemotherapy (HIVEC) treatment in a cohort of patients with high-grade non-muscle-invasive bladder cancer with bacillus Calmette-Guérin (BCG) failure or intolerance who were unsuitable or unwilling to undergo early radical cystectomy. As a secondary endpoint, we assessed the influence of some demographic, clinical and pathological factors on the response to chemo-hyperthermia. Patients and methods : Between March 2017 and December 2019, 72 consecutive patients were retrospectively analysed. Patients with diseases or conditions that could interfere with systemic inflammatory status or full blood count were excluded. The HIVEC protocol consisted of six weekly intravesical treatments with 40 mg Mitomycin-C diluted in 50 mL distilled water. The drug was heated to a temperature of 43°C. Association of categorical variables with response to HIVEC was evaluated using Yates' chi-squared test and differences in continuous variable were analysed using the Mann-Whitney test. Logistic regression analysis was performed to define independent predictors of response to HIVEC. Results : Patients who failed HIVEC were more likely to have multiple tumours ( P = 0.039) at transurethral resection of bladder and a recurrence rate of >1/year ( P = 0.046). Lower post-HIVEC inflammatory indices [C-reactive protein ( P = 0.021), erythrocyte sedimentation rate ( P = 0.027)] and lower pre- ( P = 0.014) and post-treatment ( P = 0.004) neutrophil-to-lymphocyte ratio (NLR) values were significantly associated with the response to the HIVEC regimen (no bladder cancer recurrence or progression). In the multivariate analysis, patients with a recurrence rate of >1/year were eight-times more likely to experience failure of HIVEC ( P = 0.007). Higher pre- ( P = 0.023) and post-treatment NLR values ( P = 0.046) were associated with a worse response to the HIVEC regimen. Conclusions : The recurrence rate and systemic inflammatory response markers could be useful tools to predict the likelihood of obtaining a response with the HIVEC regimen. These markers might help to guide patients about the behaviour of the tumour after BCG failure, predicting failure or success of a conservative treatment. Abbreviations: CHT: chemo-hyperthermia; CIS: carcinoma in situ ; CRP: C-reactive protein; EAU: European Association of Urology; ESR: erythrocyte sedimentation rate; HG: high grade; HIVEC: Hyperthermic IntraVEsical Chemotherapy; ICD: immunogenic cell death; IL: interleukin; MMC: Mitomycin-C; NK: natural killer; NLR: neutrophil-to-lymphocyte ratio; NMIBC: non-muscle-invasive bladder cancer; PLR: platelet-to-lymphocyte ratio; RC: radical cystectomy; SIR: systemic inflammatory response; TURB: transurethral resection of bladder., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Human schistosomiasis is a snail-borne disease caused by parasitic blood-dwelling flukes. A long-term infection can lead to the risk of liver damage, kidney failure, infertility, or bladder cancer. The most common sign is hematuria with the blood first seen in the terminal urine, but in severe cases the whole urine sample can be dark colored. We analyze the case of a healthy African child living in Italy since birth, harboring a hidden debilitating disease that was picked up during ultrasonography., Case Report: A 11-year-old African child was admitted to our emergency department with macroscopic hematuria, dysuria, and frequency for 2 months. Ultrasonography revealed a solid mass involving bladder's right wall. Non-contrast and contrast-enhanced scans of computerized tomography showed a mass of 45 mm x 15 mm on the right bladder wall. A bipolar transurethral resection of bladder was performed. The pathological examination showed findings consistent with Schistosoma haematobium., Discussion: The clinical manifestations of schistosomiasis depend on the inflammatory response to the parasitic infection. In particular, it can manifest in the bladder as painless dysuria, urinary incontinence and urinary frequency, hematuria, or even urinary retention if the trigone is involved. Utilization of ultrasonography for diagnostic evaluation of schistosomiasis is mandatory. For treatment, the World Health Organization recommends praziquantel which has an efficacy of up to 90%.

Objectives: The aim of this study was to analyse the role of two alkaloid, Protopine and Nuciferine, in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® (Hyperthermic IntraVEsical Chemotherapy) instillations., Materials and Methods: From September 2017 to September 2019, 100 patients were prospectively randomized into two groups: Group A = Protopine and Nuciferine syrup, 10 ml, once a day, for 8 weeks; Group B = placebo (flavoured coloured water), 10 ml, once a day, for 8 weeks. The primary endpoint was the evaluation of the efficacy of the therapy with Protopine and Nuciferine in controlling of the irritative symptoms. The secondary endpoint was the evaluation of the influences of the treatment on the uroflowmetric parameters., Results: The patients of Group A showed a better International Prostatic Symptoms Score (IPSS) score, a better control of urgency symptoms (PPIUS) and tolerate well the pain (VAS score). The treatment doesn't modify Uroflow-Qmax and seems to improve the Uroflow-Voided Volume (ml) without influencing the Uroflow-Post Void Residual volume (PVR). Moreover, the treatment with Protopine and Nuciferine has been proven to be effective in the treatment of overactive bladder (OAB) symptoms. Patients' evaluation of the two different treatments assessed with Patient Global Impression of Improvement questionnaire (PGI-I), demonstrated improvements in the Group A, while the Group B showed a lower satisfaction., Conclusions: Protopine and Nuciferine can be interesting nutraceutical compounds useful to control irritative and pain related symptoms of intravesical chemo/immunotherapy.

There is limited scientific literature regarding the management outcomes for end-stage erectile dysfunction (ED) following radical cystoprostatectomy (RCP). This study aims to evaluate the surgical outcomes of penile prosthesis (PP) implantation. A retrospective analysis over 17 years (2004-2017) was performed from the clinical records of patients in four tertiary referral centres, whom previously had undergone RCP, followed by PP implantation for end-stage ED. Outcome measures include both intra and postoperative complications, operative duration, a 5-point Likert hematoma scale as well as length of hospital stay. Additionally, a matched-pair cohort analysis was performed, dividing patients in 2 groups according to the type of urinary diversion (neobladder versus ileal conduit/cutaneous ureterostomy). The median time elapsed between RCP and PP implantation was 38 months (IQR 20-56). The median follow-up was 18 months (IQR 12-156). A 3-piece inflatable PP was implanted in 43 patients (91.5%) whereas a semirigid device was implanted in the remainder. Reservoir position was extra-peritoneal (utilising a separate abdominal incision) in 24 patients (54.8%), while an ectopic high-submuscular placement was preferred in the remainder. PP infection and mechanical failure occurred in 1 (2.1%) and 3 cases (6.3%) respectively. The comparative analysis of surgical outcomes did not show any statistically significant difference between the two groups. Our evidence suggests that PP implantation in patients with refractory ED following RCP may represent a safe and effective procedure associated with a low incidence of complications. The main limitation of this study is represented by the non-randomised, retrospective nature as well as the lack of patients' functional outcomes and the limited follow-up.

Introduction: Chemohyperthermia is a feasible option in BCG (bacillus Calmette-Guérin) failure patients who desire bladder preservation. We aimed to assess outcomes and complications of chemohyperthermia using mitomycin C (MMC) or epirubicin (EPI)., Material and Methods: From March 2017 to February 2020, 103 BCG failure or intolerance patients with high-risk NMIBC (non-muscle invasive bladder cancer) underwent a hyperthermic intravesical chemotherapy (HIVEC) regimen. Five patients did not complete at least 5 instillations and were excluded from analysis. MMC was used in 72 out of 98 patients (Group A) while EPI was used in 26 patients (Group B). Response to HIVEC, predictive factors for treatment outcome and the disease-free survival (DFS) were defined as primary endpoints. The complications of chemohyperthermia were assessed as a secondary endpoint., Results: No significant differences were found in recurrence and progression after induction course between Groups A and B. Kaplan-Meier disease-free survival was 22.61 months in Group A and 21.93 in Group B. The log-rank test showed no statistically significant difference between the two curves (p = .627). In the multivariate analysis, patients with tumor size ≥3 cm (p = .029), recurrence rate >1/year (p = .034), concomitant carcinoma in situ (CIS) during transurethral resection of bladder (TURB) (p = .039) and BCG-unresponsive status (p = .048) were associated with a worse response to chemohyperthermia. The use of MMC or EPI did not influence the response to treatment (p = .157). A slightly significant higher rate of overall complications (p = .0488) was observed in Group B. A significantly higher rate of Grade 3 frequency/urgency (p = .0064) contributed to this difference. The use of EPI was the only independent factor associated with severe urinary frequency/urgency (p = .017). No patients experienced Grade 4/5 adverse events., Conclusions: HIVEC can be considered a feasible option in BCG failure/intolerant NMIBC patients, avoiding or postponing radical cystectomy in some particular subclasses of patients., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

Introduction: Social distancing is considered the best strategy to prevent the spread of COVID-19 (COronaVIrus Disease 19). We aimed to analyse the effect of 'social distancing' on the emotional state, post-operative pain and functional outcomes of patients undergoing robot-assisted radical prostatectomy (RARP)., Material and Methods: We retrospectively reviewed data of male patients who underwent RARP within the study period (from March to April 2019 [Group A = 27 patients] and from March to April 2020 [Group B = 29 patients]). Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) results were collected on the first day of hospitalization. Post-operative pain was assessed using the numerical rating scale (NRS) and visual analogic scale (VAS) after surgery in the post-anesthesia care unit (PACU) and at 24 hours. Functional outcomes were evaluated at the one-month follow-up. Demographic, pathological and peri-operative data were collected for all patients., Results: There were no significant differences in demographics and pathological characteristics amongst the groups. We observed that patients in Group A had a statistically lower value on the PHQ-9 and GAD-7 questionnaires than patients of Group B. Moreover, Group A showed statistically significant better post-operative pain control in PACU and at 24 hours. At one-month follow-up, patients in Group B required more diapers for incontinence than Group A, showing poor early continence. Patients in Group A showed interest in sexual rehabilitation after 1.11 ±.320 months while patients in Group B after 2.59 ±.712 months (p <.001). Moreover, 17 out of 29 patients (58.62%) in Group B were referred to an andrologist, compared to 100% of patients from Group A (p = 0.0006)., Conclusions: Social distancing during the COVID-19 pandemic is associated with a poor pre-operative emotional state, as well as influencing post-operative pain, early urinary continence and desire for sexual rehabilitation., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

Introduction: To evaluate the efficacy of Bifiprost® + Serenoa Repens 320 mg versus Serenoa Repens 320 mg alone for the prevention of chronic bacterial prostatitis (CBP) due to enterobacteriaceae., Methods: Between September 2016 and September 2018, 120 patients with CBP at the National Institutes of Health (NIH type II) with recurrent infections due to enterobacteriaceae (Escherichia Coli and Enterococcus faecalis) were enrolled and randomized into 2 groups each to receive Bifiprost® + Serenoa Repens 320 mg (Group A) or Serenoa Repens 320 mg alone (Group B) daily for 24 weeks (after receiving a proper antibiotic treatment with subsequent culture negativization). The primary endpoint was the reduction in the episodes of prostatitis. The secondary endpoint evaluated was the score of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI). Evaluation was performed at baseline and at 12, 24, and 36 weeks., Results: The patients of the Group A experienced a significantly larger reduction in the prostatitis episodes than the Group B at 24 and 36 weeks, but they did not experience a significantly larger reduction at 12 weeks. After 12 weeks of treatment, the mean NIH-CPSI score was reduced in both groups compared with baselines, but no significant differences were seen between the Group A and Group B. On the contrary, we observed a significant difference in the mean NIH-CPSI score between the 2 groups at 24 and 36 weeks., Conclusion: The association of Bifiprost® and Serenoa Repens 320 mg improves the prevention of the episodes of CBP due to enterobacteriaceae and ameliorates prostatitis-related symptoms after 6 months of therapy. The long-term impact on the entero-urinary route was also seen 3 months after the end of the treatment., (© 2019 S. Karger AG, Basel.)

Introduction: Leiomyomas are benign mesenchymal tumours of smooth muscle origin. They are the most common uterine masses in women of reproductive age group and may be related to the hormonal status. Urethral leiomyomas are very rare. According to the literature, the mean diameter of the urethral leiomyomas is 3.7 cm., Case Report: We report a case of a very large leiomyoma of the urethra. A 40-year-old women woman was admitted to our department for a giant vaginal mass. She complained of haematuria, dysuria, recurrent urinary tract infections and dyspareunia. The physical evaluation demonstrated a 6 × 5.5 cm neoformation involving the distal tract of the urethra. The patient underwent an ultrasonography and then a magnetic resonance that suggested the diagnosis of leiomyoma. The neoformation was excised through a suburethral incision., Conclusions: The patient was discharged after 3 days and no intraoperative and postoperative complications occurred. The Foley catheter was removed after a week. The patient was continent to urine, and at 6 months follow-up, the patient was symptom free and no recurrences occurred.

Objective: To assess the efficacy and safety of an association of diallyl thiosulfinate with nuciferine and diosgenin in the treatment of a group of patients suffering from premature ejaculation (PE), primary or secondary to erectile dysfunction (ED)., Materials and Methods: From July 2015 to October 2016, 143 patients (mean age 25.3; range 18-39) affected by PE completed the study and were finally analyzed in this phase I study. All patients, after clinical assessment and laboratory evaluation were asked to take an association of diallyl thiosulfinate with nuciferine and diosgenin as oral tablet, once a day, on alternate days, for three months. At the baseline and after three months of treatment, each patient was asked to complete the following questionnaires: International Index of Erectile Function (IIEF-5), Premature Ejaculation Diagnostic Tool (PEDT), Male Sexual Health Questionnaire (MSHQ)., Results: A statistical significant improvement in terms of erectile function, comparing the IIEF-5 value at baseline and follow- up visit was found (respectively IIEF-5: 8.7 vs 14.01; p < 0.001). Moreover, at follow-up visit, 97/143 men (67.8%) referred a subjective improvement of the erection quality and a better control of the ejaculation (PROs). The IELT improved too between the baseline evaluation and the follow-up visit (p < 0.001)., Conclusion: In conclusion, our study, even if supported by preliminary results, showed how Diallyl Thiosulfinate, Nuciferine and Diosgenin is able to improve the control of ejaculation in patients suffering from PE, primary or secondary to ED without any significant adverse effects.

Purpose: To describe and analyze our experience with Anderson-Hynes transperitoneal laparoscopic pyeloplasty (LP) in the treatment of recurrent ureteropelvic junction obstruction (UPJO)., Materials and Methods: 38 consecutive patients who underwent transperitoneal laparoscopic redo-pyeloplasty between January 2007 and January 2015 at our department were included in the analysis. 36 patients were previously treated with dismembered pyeloplasty and 2 patients underwent a retrograde endopyelotomy. All patients were symptomatic and all patients had a T1/2>20 minutes at pre-operative DTPA (diethylene-triamine-pentaacetate) renal scan. All data were collected in a prospectively maintained database and retrospectively analyzed. Intraoperative and postoperative complications have been reported according to the Satava and the Clavien-Dindo system. Treatment success was evaluated by a 12 month-postoperative renal scan. Total success was defined as T1/2≤10 minutes while relative success was defined as T1/2between 10 to 20 minutes. Post-operative hydronephrosis and flank pain were also evaluated., Results: Mean operating time was 103.16±30 minutes. The mean blood loss was 122.37±73.25mL. The mean postoperative hospital stay was 4.47±0.86 days. No intraoperative complications occurred. 6 out of 38 patients (15.8%) experienced postoperative complications. The success rate was 97.4% for flank pain and 97.4% for hydronephrosis. Post-operative renal scan showed radiological failure in one out of 38 (2.6%) patients, relative success in 2 out of 38 (5.3%) patients and total success in 35 out of 38 (92.1%) of patients., Conclusion: Laparoscopic redo-pyeloplasty is a feasible procedure for the treatment of recurrent ureteropelvic junction obstruction (UPJO), with a low rate of post-operative complications and a high success rate in high laparoscopic volume centers., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: In recent times there has been a trend in mininvasive renal tumour surgery. Very limited evidence can be found in literature of the outcomes of laparoscopic partial nephrectomy (LPN) for highly complex renal tumours. The aim of the present study was to assess the feasibility and safety of LPN for renal tumours of high surgical complexity in our single-institutional experience, comparing perioperative and functional data between clampless and clamped procedures., Materials and Methods: We enrolled 68 patient who underwent a clampless LPN (Group A) and 41 patients who underwent a clamped LPN (Group B) for a renal tumour with a R.E.N.A.L. NS ≥ 10. Intraoperative and post-operative complications have been classified and reported according to international criteria. Kidney function was evaluated by measuring serum creatinine concentration and eGFR., Results: Group A was found to be similar to Group B in all variables measured except for WIT (P = 0) and blood loss (P = 0.0188). In group A the mean creatinine levels were not significantly increased at the third post-operative (P = 0.0555) day and at the 6-month follow-up (P = 0.3047). Otherwise, in the group B the creatinine levels were significantly increased after surgery (P = 0.0263), but decreased over time, showing no significant differences at 6 month follow-up (P = 0.7985) compared to preoperative values. The same trend was seen for eGFR. Optimal Trifecta outcomes were achieved in both groups., Conclusions: Clampless LPN represents a feasible and safe procedure, even for tumours with high surgical complexity, in highly experienced laparoscopic centers. When compared to clamped LPN, it results in better preservation of immediate post-operative renal function.

Introduction: Distal extrusion of cylinders is a potential complication of the penile prosthesis implantation. Several methods have been proposed for repairing a distal penile erosion. We present our preliminary experience in "Distal corporoplasty" technique., Methods: We enrolled 18 consecutive patients whose underwent a distal corporoplasty with simultaneous reimplantation of an "AMS 700 inflatable penile prosthesis (LGX)" from January 2013 to November 2015 at our hospital. All procedures were performed by a single surgical team. Intraoperative and postoperative complications have been classified and reported according to Satava6 and Clavien-Dindo (CD) system.7 Mean values with standard deviations (±SD) were computed and reported for all items., Results: Mean age of the patients was 53.61 (±11.90) years. Mean body max index (BMI) was 24.22 (±2.51). Mean operative time was 85.2 (±13.1) minutes. Blood losses were minimal. No intraoperative complications are reported according to Satava classification. Four out of 18 patients (22.22%) experienced postoperative complications according to CD system. All patients had sexual intercourse for the first time postsurgery after a mean of 59.11 ± 2.08 days. Mean follow-up was 22.11 (±9.95)., Discussions: Distal extrusion of cylinders is a potential complication of the penile prosthesis implantation. Distal corporoplasty was first described by Mulcahy. He reported a series of 14 patients with a follow-up of about 2 years with optimal functional outcomes. Moreover, distal corporoplasty resulted in shorter operative time, better function, less pain, and fewer recurrences than Gortex windsock repair.10 In our experience, distal corporoplasty is a simple and safe procedure in the treatment of distal cylinders extrusion when the prosthetic material is not exposed to the exterior.

Spondylodiscitis is an inflammation of the intervertebral disc and the adjacent vertebral bodies. The spondylodiscitis can not only be a complication of medical interventions such as an operation near spinal column but also urogenital and vascular interventions and intravenous catheter use. A 71-year-old man was admitted to our emergency department with fever and severe abdominal pain. Antibiotic therapy had been performed with intravenous administration of 2 g of ceftriaxone and the patient underwent the placement of a percutaneous nephrostomy according to Seldinger technique. After 1 week, the patient experienced a severe pain at the lumbar tract of the vertebral column associated with a moderate abdominal pain and septic fever. A magnetic resonance imaging (MRI) of the lumbar spine showed widespread impregnation of the upper portion of L3 and the lower portion of L2 compressing the spinal roots as well as the ileopsoas muscle such as a spondylodiscitis. Liquor culture showed an increase of liquor immunoglobulin G, total liquor protein and was positive for Extended-spectrum beta-lactamases (ESBL) - producing Escherichia coli. After the antibiotic therapy, the spondylodiscitis resolves without important sequelae. In the present case report, we describe a very rare complication of percutaneous nephrostomy tube placement, despite of the prophylactic antibiotic therapy according to the most recent guidelines. Predisposing factors to spondylodiscitis include the very young and elderly, the immunosuppressed, diabetic individuals and a general debilitating disease such as renal failure. This case suggests the importance of remembering spondylodiscitis when septic fever and back pain occurs following the placement of a percutaneous nephrostomy in a septic patient.

Common complications related to transrectal ultrasound (TRUS) guided prostatic needle biopsy are hematuria, hematospermia, and hematochezia. To the best of our knowledge, we report the second case of a very large hematoma extending from the pelvis into the retroperitoneal space in literature.A 66-year-old man with a serum prostate-specific antigen (PSA) of 5.4 ng/ml was admitted to our department for a TRUS-guided prostatic needle biopsy. Laboratory values on the day before biopsy, including coagulation studies, were all normal. The patients did not take any anticoagulant drugs. No immediate complications were encountered. Nevertheless, 7 hours after the biopsy, the patient reached our emergency department with severe diffuse abdominal pain, hypotension, tachycardia, and confusional state. He underwent an ultrasonography and then a computed tomography (CT) scan that showed "a blood collection in the pelvis that extending to the lower pole of left kidney associated with a focus of active contrast extravasation, indicating active ongoing prostate bleeding." Consequently, he underwent a diagnostic angiography that showed no more contrast extravasation, without the need of embolization. Management of hematoma has been conservative and hematoma was completely reabsorbed 4 months later.

Angiomyolipoma (AML) is the most common benign tumour of the kidney and is composed of smooth muscle cells, blood vessels and fat elements. AMLs are usually casually discovered when the kidneys are imaged for other reasons. Their first presentation is often a spontaneous retroperitoneal haemorrhage or bleeding into the urinary collection system, which can be life-threatening. The bleeding tendency is related to the irregular, aneurysmal, tortuous blood vessels that compose the tumor. The greatest risks for bleeding are tumour size and grade of the vascular component of the tumour. Moreover, the risk of bleeding is proportional to the size of the lesion (it is higher in AMLs with a diameter more than 4 cm). Shock due to a grave haemorrhage from AML rupture is called Wunderlich syndrome that is clinically characterized by the Lenk's triad: acute flank pain, a flank mass and hypovolemic shock.Other symptoms and signs may be present: haematuria, palpable mass, flank pain, urinary tract infections, renal failure or hypertension. Small AMLs usually require no therapy, although follow-up is recommended in order to follow its growth. Larger or symptomatic lesions can be electively embolized and/or resected with a partial nephrectomy. AMLs that present with retroperitoneal haemorrhage frequently require emergency embolization. We describe a case of an actively bleeding small renal AML, with a rapid growth, without any evidence for big aneurysmal vessels, who underwent an emergency embolization at our hospital.

Nm23-H1 has been identified as a metastatic suppressor gene in murine melanoma cell lines. Several functions have been attributed to its activity in cancer, including a histidine kinase activity, DNA repair, and regulation of other proteins involved in metastatic formation. While in breast cancer, NM23-H1 overexpression indicates a benign status through impairing progression of disease, its function is opposite in other cancers; e.g., neuroblastoma. To further understand this dichotomy of function in cancer, we have analyzed its function in prostate cancer, in which the relationship between NM23-H1 expression and prognostic state is today controversial. In vitro, overexpression of NM23-H1 in PC3 cells inhibited their cell motility, while downregulation of NM23-H1 expression in these cells by RNA interference showed enhanced cell motility. Immunohistochemistry analysis performed on 346 prostate cancer tissue samples showed a relationship between high levels of NM23-H1 expression in the nuclei of these tumorigenic cells and elevated Gleason score, with high levels of NM23-H1 cytoplasmic staining related to metastatic stage. This retrospective survival study demonstrates that high levels of NM23-H1 expression in the cytoplasm determine recurrence of prostate-specific antigen levels only in those patients with metastatic disease. Our findings suggest a correlation between high levels of NM23-H1 protein in the cytoplasm of the cells and progression of prostate cancer to metastasis, thus definitively identifying NM23-H1 as a new negative prognostic marker in prostate cancer.

The Morris syndrome is a X-linked recessive condition due to a complete or partial insensitivity to androgens, resulting in a failure of normal masculinization of the external genitalia in chromosomally male individuals. This failure of virilization can be either complete or partial depending on the amount of residual androgen receptor function. The phenotype of individuals with partial androgen insensitivity syndrome may range from mildly virilized female external genitalia to mildly undervirilized male external genitalia. We describe a case of Partial Androgen Insensitivity Syndrome in a 21-year-old patient with a 46, XY karyotype, bilateral inguinal masses, clitoral enlargement and partial posterior labial fusion. Surgical care consisted of bilateral orchiectomy and plastic surgery of external genitalia. The patient underwent estrogen replacement therapy.

A loading dose of tryptophan induces a marked increase of tryptophan-pyrrolase (substrate induction) and a decrease of 3-OH-anthranilic-oxidase values in rat liver; in the kidneys of the same experimental animals the 3-OH-anthranilic-oxydase is instead unchanged. In other experimental conditions (surrenectomized or pyridoxine depleted rats, with or without tryptophan loading; with prednisolone loading) a more or less important substrate induction is always reported, whereas no variation occurs in the values of 3-OH-anthranilic-oxydase. These data are not sufficient to state whether there is a connection between the opposite responses of the two enzymatic activities obtained after tryptophan loading in rat liver homogenate. On the other hand, it should be kept in mind that they do not represent the overall effect induced by the aminoacid loading, but refer only to one moment of the action exerted by the loading itself. In order to acquire a thorough knowledge of the observations made so far and to formulate some assumptions which may be helpful for the interpretation of the relevant mechanisms, it is necessary to investigate the kinetics of both enzymes, and to study their regulatory mechanisms in particular after tryptophan loading.

The incorrect use of the terms vitamin overdosage and overload, hypervitaminosis and dysvitaminosis gives rise to errors in the classification and evaluation of their etiology and pathogenesis. Vitamin overdosage and overload are observed with every vitamin and produce high blood and tissue levels of the vitamin itself; however, the overdosage can be obtained only upon administration of high doses of a vitamin, while vitamin overload may originate from a variety of factors. Hypervitaminoses are known for vitamin A and D; they are accompanied by high blood levels, but are characterized by a specific symptomatology. The term dysvitaminosis comprises "every alteration of the physiological status of the vitamin, in terms of both its deficiency and its surplus". These considerations provide a unitary view of vitamin pathology and lead to the following proposal of an etiopathogenetic classification of dysvitaminoses: class A) dysvitaminoses due to overload, class B) dysvitaminoses due to deficiency. Each class in turn may be divided into congenital and acquired syndromes. In class A) the congenital syndromes are still not well known, the acquired syndromes comprise those with hypervitaminosis (hypervitaminosis A and D) and those without hypervitaminosis (for the other vitamins). In class B) the congenital syndromes comprise diseases produced by inborn enzymatic errors and by other etiologies, the acquired syndromes can be distinguished in physiological (age, pregnancy, etc.) and pathological (nutritional, iatrogenic, etc.) ones. On this basis hypervitaminoses A and D can be considered as non obligatory dysvitaminoses due to overload; their origin has a complex etiology, since the liposolubility of the vitamins and the prolonged use of high dosages are not the only factors responsible for the hypervitaminosis.

The problem of the relationship between the thiamine and autonomic system drugs was studied about 30 years ago. To the vitamin was attributed an excitatory effect upon the peripheric section of parasympathetic nervous system and a synergic action with acetylcholine. Both an acetylcholine-like substance and thiamine are liberated at the nerve terminals after a stimulation. A similar synergic action of thiamine with adrenaline was also demonstrated. The study of the relationship between these drugs and the vitamin B1 is also now interesting. We want to stimulate a new series of experiments on this subject with the reprint of this review.

The concept of "drug induced avitaminoses" originates from the observation that drugs may cause vitamin deficiencies. These avitaminoses belong to the "iatrogenic disvitaminoses" and can be subdivided into two groups since they may either represent unwanted side effects of a drug or may be utilized for therapeutical purpose. In the latter case they can be considered as "planned avitaminoses". All drugs are generally able to produce a deficiency of one or more vitamins and therefore have a "devitaminizing power". It would be desirable to quantify this property of drugs in terms of a "devitaminization index". Knowledge of this index, which should be acquired for new drugs during clinical research, is of primary importance since it allows to adapt the dosage and use of the drug to the vitaminic status of the patient and enables to foresee and prevent damages due to vitamin deficiency. Drug induced avitaminioses are produced more easily and are more severe if the devitaminizing power of the drug and its dosage are high, the therapy is long and the vitaminic status of the patient is optimal. Many subjects (old people, children, etc.) have an elevated risk of avitaminoses. Drug induced avitaminoses are produced by mechanisms acting both at the intestinal level (absorption, endogenous production, etc.) and at the tissue level (metabolism, utilization, etc.). Some of the mechanisms have not been completely clarified. These avitaminoses are numerous and frequent, but their prevention is relatively easy and always achievable. They constitute a new disease and cause an additional damage with respect to the primary illness. The social and economic aspects of this damage are evident considering that many pharmacological profilactic and therapeutic treatments of social illnesses, such as diabetes, tuberculosis, epilepsy, rheumatic diseases, etc. have a devitaminizing power. It is clear therefore that this pathology is particularly important in preventive medicine and that it must be known not only by practitioners and biologists but also outside the medical field.

The concept of risk in the field of avitaminoses is very important and useful for the practitioner, who should consider two aspects: a) risk factors, which could be individual (physiological, pathological and psychological) and extra-individual (alimentary, environmental, etc.); b) subjects with an elevated risk of avitaminosis (childhood, old age, pregnancy, etc.). In these subjects the risk can be a generical one, when there is an elevated requirement for all vitamins (nursing women, sportmen, etc.) or a specific one, when there is a high requirement only for a single vitamin (osteomalacia, some professional diseases, use of oral contraceptives) or a vew of them (alcoholism, diabetes, etc.). On the basis of this kind of knowledge it is easy for the practitioner to estimate which vitamins are necessary for each subject or for a group of subjects in physiological or in pathological conditions. For example, there is an elevated risk of apyridoxinosis in old age (acalciferolosis in aged women), of athiaminosis and apyridoxinosis in diabetes, of apyridoxinosis in oral contraceptives users, of axeroftolosis in hyperthyroidism, of athiaminosis, apyridoxinosis, aniacinosis and anascorbosis in alcoholics. In the second chapter the concept of the latency period in avitaminosis is illustrated. This period corresponds to the interval between the moment when deficiency stimulus starts operating and the moment when its effect, that is the picture of avitaminosis, appears. The latency time is not measurable, on account of the difficulties in establishing the onset of the deficiency stimulus; generally it is very long and is followed by the period of biochemical symptomatology and subsequently by the one of clinical symptomatology. Each of these three phases can be further divided in several steps, which have summarized in a Table. The last chapter is dedicated to the classification of avitaminoses. From the etiopathogenetic point of view avitaminoses can be due to: a) deficiency of introduction (alimentary level)); b) deficiency of absorption (enteric level); c) deficiency of utilization (tissue level). From the clinical point of view avitaminoses can be distinguished in deficiency with: a) a complete clinical symptomatology (scurvy, beriberi, pellagra, rickets, osteomalacia, xerophthalmia, hemeralopia); b) an incomplete clinical symptomatology (mono- or oligo-symptomatic or partial clinical picture); c) a biochemical symptomatology only (subclinic or clinically asymptomatic picture).