Robot-assisted radical cystectomy with totally intracorporeal urinary diversion: surgical and early functional outcomes through the learning curve in a single high-volume center.

The aim of the study is to report surgical and early functional outcomes of first 100 patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD) in a single center. The main surgeon (A.P.) attended a modular training program at a referring center mentored by a worldwide-recognized robotic surgeon (P.W.). The program consisted of: (a) 10 h of theoretical lessons; (b) video session (c) step-by-step in vivo modular training. Each procedure was performed as taught, without any technique variation. Demographics, intra-operative data and post-operative complications, along with early functional outcomes, were recorded for each patient. We retrospectively evaluated the first consecutive 100 patients submitted to RARC with totally ICUD from July 2015 to December 2018. Median age at surgery was 69 years (IQR 60-74). 52 (52%), 32 (32%), and 17 (17%) patients received orthotopic neobladder, ileal conduit and uretero-cutaneostomy, respectively. Median operative time was 410 min. A median number of lymph nodes retrieved were 27 and median estimated blood loss was 240 mL with median hospitalization time of 7 days. All procedures were completed successfully without open conversion. A statistically significant improvement was found in the late (30-90 post-operative days) post-operative complications (p = 0.02) and operative time for urinary derivation. At multivariate logistic regression model ASA score ≥ 3 (OR = 4.2, p = 0.002) and number of lymph nodes retrieved (OR = 1.16, p = 0.02) were found to be predictors of 90-day complications. An adequate modular training is paramount to obtain successful results and reduce the learning curve of RARC, as demonstrated by our experience.

Retroperitoneal approach for robot-assisted partial nephrectomy: technique and early outcomes

ABSTRACT Objectives The aim of our study is to present early outcomes of our series of retroperitoneal-RAPN (Robot Assisted Partial Nephrectomy). Materials and methods From September 2010 until December 2015, we performed 81 RAPN procedures (44 at left kidney and 37 at right). Average size was 3cm (1-9). Average PADUA score 7.1 (5-10). Average surgical time (overall and only robot time), ischemia time, blood loss, pathological stage, complications and hospital stay have been recorded. Results All of the cases were completed successfully without any operative complication or surgical conversion. Average surgical time was 177 minutes (75-340). Operative time was 145 minutes (80-300), overall blood loss was 142cc (60-310cc). In 30 cases the pedicle was late clamped with an average ischemia time of 4 minutes (2-7). None of the patient had positive surgical margins at definitive histology (49pT1a, 12pT1b, 3pT2a, 2pT3a). Hospital stay was 3 days (2-7). Conclusions The retroperitoneal robotic partial nephrectomy approach is safe and allows treatment of even quite complex tumors. It also combines the already well known advantages guaranteed by the da Vinci® robotic surgical system, with the advantages of the retroperitoneoscopic approach.

Retroperitoneal approach for robot-assisted partial nephrectomy: technique and early outcomes.

OBJECTIVES: The aim of our study is to present early outcomes of our series of retroperitoneal-RAPN (Robot Assisted Partial Nephrectomy). MATERIALS AND METHODS: From September 2010 until December 2015, we performed 81 RAPN procedures (44 at left kidney and 37 at right). Average size was 3cm (1-9). Average PADUA score 7.1 (5-10). Average surgical time (overall and only robot time), ischemia time, blood loss, pathological stage, complications and hospital stay have been recorded. RESULTS: All of the cases were completed successfully without any operative complication or surgical conversion. Average surgical time was 177 minutes (75-340). Operative time was 145 minutes (80-300), overall blood loss was 142cc (60-310cc). In 30 cases the pedicle was late clamped with an average ischemia time of 4 minutes (2-7). None of the patient had positive surgical margins at definitive histology (49pT1a, 12pT1b, 3pT2a, 2pT3a). Hospital stay was 3 days (2-7). CONCLUSIONS: The retroperitoneal robotic partial nephrectomy approach is safe and allows treatment of even quite complex tumors. It also combines the already well known advantages guaranteed by the da Vinci® robotic surgical system, with the advantages of the retroperitoneoscopic approach.

Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort.

INTRODUCTION: Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. MATERIALS AND METHODS: A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. RESULTS AND LIMITATIONS: 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). CONCLUSIONS: In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way.

Benign fibrous histiocytoma of the small intestine in a cow.

A well circumscribed, firm nodule was found protruding from the duodenal wall of an adult cow at routine meat inspection. On the basis of morphological and immunophenotypic features, a diagnosis of benign fibrous histiocytoma (BFH) was established. Malignant fibrous histiocytoma has been reported previously in the cow, albeit rarely, but to the best of our knowledge this is the first recorded case of bovine intestinal BFH.

Hepatic biliary adenofibroma: a hitherto unrecognized tumor in equines. Report of a case.

Hepatic biliary cystadenoma is a well-delineated neoplasm in some domestic animals, especially in cats, but it has not been reported in equines. We report on a case of hepatic biliary tumor, incidentally found in a 10-year-old horse, with gross and microscopic features similar to those observed in biliary adenofibroma of humans. The tumor presented as a solid mass measuring 16 cm in diameter and histologically was composed of complex tubulocystic biliary components embedded in an abundant fibrotic stroma. We regarded this tumor as a morphological variant of biliary cystadenoma of domestic animals. Differential diagnoses from other hepatic biliary tumor-like and tumor lesions are provided.

Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis.

We have studied the effects of treatment with recombinant human (rh)IL-6 on clinical, histological and immunological parameters of protracted relapsing (PR) experimental allergic encephalomyelitis (EAE) in DA rats. rhIL-6 (50 microg/rat subcutaneously/day) was given under three different regimens, as early prophylaxis, from 1 day prior to 14 days after immunization, in late prophylaxis, from day +7 until day 21 post-immunization (p.i.) and therapeutically to rats with clinical signs of EAE from day 14 to day 28 p.i. Although rhIL-6 failed to modulate the course of PR-EAE when administered as the early prophylactic regimen, it exerted clear-cut favourable effects on the course of the disease if was administered either as later prophylactic or as therapeutic treatment. Under these conditions, rhIL-6 accelerated recovery from EAE attacks and reduced/milded subsequent EAE episodes as compared to either PBS- or heat-inactivated rhIL-6-treated control rats. In agreement with this clinical effect, relative to PBS-treated rats, the animals injected with rhIL-6 exhibited lower numbers of MHC class II(+) and CD4(+) cells in their spinal cords. rhIL-6-treatment also profoundly modulated the endogenous cytokine network, the treated rats displaying increased numbers of spleen cells expressing mRNA transcripts of the anti-inflammatory cytokines IL-10 and TGF-beta along with simultaneously reduced numbers of mRNAs for TNF-alpha. In addition, upon ex vivo exposure to either myelin basic protein peptide 63-88 (MBP63-88) or to phytoaemagglutinin A, the numbers of IFN-gamma secreting splenocytes was also significantly reduced (ELISPOT analysis) in rhIL-6-treated rats as compared to PBS-treated controls.

Murine concanavalin A-induced hepatitis is prevented by interleukin 12 (IL-12) antibody and exacerbated by exogenous IL-12 through an interferon-gamma-dependent mechanism.

Concanavalin A (ConA)-induced hepatitis is a cell-mediated immunoinflammatory condition similar to human autoimmune hepatitis. We investigated the role of interleukin 12 (IL-12) in hepatitis induced in NMRI and C57/BL6 mice by a single injection of ConA. Recombinant murine IL-12 administered 24 hours and 1 hour prior to ConA exacerbated both transaminase activities in plasma and histologic signs of hepatitis. These markers of liver injury were significantly reduced by prophylactic, but not therapeutic treatment with anti-IL-12 monoclonal antibody (mAb). The disease-modulatory effects of IL-12 and anti-IL-12 mAb were associated with profound and reverse modifications of a ConA-induced increase in the circulating levels of IL-4, IL-6, interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). Relative to control animals receiving ConA alone, the plasma levels of these cytokines were all augmented in IL-12/ConA-treated mice and diminished in anti-IL-12 mAb/ConA-treated mice. Anti-IFN-gamma mAb also impeded the appearance of IL-12/ConA-induced hepatitis. Thus, IL-12-induced production of IFN-gamma might play a role in mediating the hepatitis-inducing effect of ConA. However, IL-12p40-deficient C57/BL6 mice were as susceptible as wild-type controls to the hepatitis-inducing effect of ConA.

Immunization with both T cell-dependent and T cell-independent vaccines augments HIV viral load secondarily to stimulation of tumor necrosis factor alpha.

Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4 cell counts, and might influence disease progression. Because these deleterious effects are postulated to be secondary to a direct activation of T lymphocytes induced by the immunogen, we compared immunologic and virologic effects of a T cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO) (T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and 28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and 6 months after vaccination were not significantly different. HIV viral load increased in both groups of children despite the fact that type 1 cytokine production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of T cell activation (as measured by cytokine production) was observed in PNEUMO-vaccinated children. Because polysaccharides of the bacterial cell wall stimulate TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate HIV replication directly on activation of NF-kappa b after binding the long terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and observed a significant increase in both groups of vaccines. These data suggest that an increase in HIV viral load can be observed in vaccinated HIV-infected children even independent of direct antigen-induced activation of T lymphocytes, and that augmented production of TNF-alpha might play a role in this phenomenon.

Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.

Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.

Long-term resistance to HIV infection in vertical HIV infection: cytokine production, HIV isolation, and HIV phenotype define long-term resistant hosts.

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

Ultrasonographic surveillance after surgery for euthyroid goitre in patients treated or not with thyroxine.

OBJECTIVE: To assess the efficacy of postoperative treatment with I-thyroxine in patients operated on for euthyroid goitre after precise definition of extent of goitre disease preoperatively and postoperatively by ultrasound. DESIGN: Retrospective study in a selected population. SETTING: University hospital, Italy. SUBJECTS: 53 patients operated on from 1984 to 1994 for euthyroid goitre. INTERVENTIONS: 13 patients who had contralateral disease had lobectomy and contralateral enucleation and were treated postoperatively with suppressive doses of thyroxine. 22 patients underwent lobectomy with no medication. 18 patients underwent subtotal thyroidectomy followed by thyroxine in substitution doses. All patients had regular clinical assessments and ultrasound examination for evidence of recurrent disease. RESULTS: There were no significant differences in the incidence of relapses between those who had lobectomy and those who had lobectomy plus enucleation (p > 0.05). CONCLUSIONS: We found no significant evidence that postoperative suppressive treatment had any effect on recurrence of goitre. Subtotal thyroidectomy gave the lowest recurrence rate (p = 0.14).

Myocardial revascularization in patients with ischemic cardiomyopathy: functional observations.

OBJECTIVE: A prospective angiographic study was undertaken to investigate, with an objective analysis, the global and regional wall response to myocardial revascularization. METHODS: Thirty-one patients (30 men and 1 woman, mean age, 61 years) with a left ventricular ejection fraction of less than 0.30 were admitted to our institution between 1992 and 1995 for two- or three-vessel coronary artery disease requiring myocardial revascularization. All patients underwent isolated coronary artery bypass grafting and were studied 3 months later with angiography. Preoperative and postoperative wall motion were analyzed using special software that computed a segmental left ventricular ejection fraction, generating a segmental score. Computerized analysis allowed us to distinguish patients with diffuse hypokinesis and a symmetric contraction pattern from patients with akinesis involving at least two segments and an asymmetric contraction pattern. RESULTS: There were no operative deaths and no patient required intraaortic balloon counterpulsation. One patient had postoperative enzymatic evidence of myocardial infarction. Postoperative angiography showed a graft patency rate of 84%. Global analysis showed a small but significant rise in the left ventricular ejection fraction (0.25 +/- 0.51 to 0.31 +/- 0.70, p < 0.001) and a fall in the left ventricular end-diastolic pressure (23.7 +/- 10 to 16.5 +/- 9 mm Hg, p < 0.01). Mean scores always have been lower after the operation than before it, with the best results obtained for the apex and the worst for the anterobasal segment. The group with a symmetric contraction pattern showed a trend toward a better hemodynamic response than the group with an asymmetric contraction pattern. Regression analysis revealed two important predictors of segmental functional improvement: (1) the absence of an echocardiographic scar, and (2) the presence of a collateral circulation. CONCLUSIONS: Coronary artery bypass grafting produced a small but substantial improvement in patients with ischemic cardiomyopathy. The greater benefit occurred in patients with a symmetric contraction pattern. The absence of an echocardiographic scar and the presence of a collateral circulation predicted segmental functional improvement.

Virologic and immunologic markers of disease progression in pediatric HIV infection.

Correlates of progression of human immunodeficiency virus (HIV) infection to AIDS include the reduction in CD4+ T cells and the emergence of syncytium-inducing (SI) HIV variants. It has been suggested that progressive defects in interleukin 2 (IL-2), IL-12, and IFN- gamma production (type 1 cytokines), and increased production of IL-4 (and of IL-4-driven hyper-IgE), IL-6, and IL-10 (type 2 cytokines), could provide another correlate of disease progression. To determine the possible association among these markers, viral phenotype, cytokine production, IgE serum concentration, and rate of CD4 depletion were analyzed in a cohort of vertically HIV-infected children. We report that significantly higher production of type 2 cytokines and augmented IgE concentration are observed in children in whom HIV SI is isolated. In addition, we observed that the isolation of HIV SI and the production of high quantities of type 2 cytokines are correlated with increased loss of CD4 T cells in the 12 months preceding the determinations. These data suggest that the virologic and immunologic parameters characteristic of advanced HIV infection may be associated in pediatric HIV infection, and indicate a virologic-immunologic pathogenesis leading to the appearance of AIDS.

Respiration in NREM and REM sleep after upper airway surgery for obstructive sleep apnoea.

To verify whether upper airway surgery in obstructive sleep apnoea syndrome affects differently respiration in NREM and REM sleep, 22 patients were studied by polysomnography before and three months after surgical treatment. On the average, treatment improved respiration during both sleep states, but no significant interaction was found between sleep state and effect of surgical treatment. According to the response to treatment, three groups of patients were identified: the first group (N = 6), with an improvement in apnoea-hypopnoea index (AHI), percentage of sleep time spent in apnoea and hypopnoea (time in AH) and mean oxyhaemoglobin saturation (SaO2) in both NREM and REM sleep; the second group (N = 5), with an improvement in AHI only in NREM sleep, associated with improvement in mean SaO2 in both sleep states; the third group (N = 11), without any improvement in AHI and time in AH, either associated (N = 5) or not (N = 6) with an improvement in mean SaO2 in both sleep states. An increase in the percentage of hypopnoeas out of the total AHI after treatment could partly account for the apparent discrepancy between AHI and mean SaO2 behaviour in the subjects of the second group, but not in the patients of the third group who improved their mean SaO2. Mixed apnoeas occurred before surgery in six subjects; they remained numerous after surgery only in two subjects who did not show any SaO2 improvement. In conclusion, the degree of improvement in respiration after upper airway surgery was similar in every patient in NREM and REM sleep.

[The surgical treatment of obstructive sleep apnea syndrome]. / La terapia chirurgica nella sindrome dell'apnea ostruttiva nel sonno (OSAS).

Studies concerning the anatomical abnormalities of upper airways in patients affected by Obstructive Sleep Apnea Syndrome (OSAS) allowed the corrective surgical treatments in this syndrome. To provide an improvement or a definitive recovery of OSAS, various surgical treatments, i.e. functional nasal surgery, palatal surgery [Partial resection of palate (RPP), Uvulopalatopharingoplasty (UPPP), Palatopharingoplasty (PPP), modified Palatopharingoplasty (modified PPP)], mandibular and base tongue surgery, have been performed in order to obtain an enlargement of upper airways. It has been reported that in RPP, UPPP, PPP and modified PPP partial or total uvula and soft palate resection is conduct; in our research we performed modified PPP. 44 OSAS patients, severe or moderately severe form (polisomnographic diagnosis), underwent surgical treatment: 5 patients underwent functional nasal surgery; 9 patients underwent modified PPP; 29 patients underwent nasal and palatal surgery; only 1 patient underwent base tongue surgery. 32 patients underwent polisomnographic records after surgery (two months later) and we evaluated Apnea Index (I.A.) and a SaO2 low (nadir) with statistic tests. The results have been positive. Therefore, we have now 7 normal, 2 mild form, 7 moderate form, 3 moderately severe form and 13 severe form OSAS patients. If, on the one hand, all these surgical treatments can be considered a good way of therapy, on the other, only tracheostomy represents today the unfailing surgical therapy.

Recurrence of goitre after operation in euthyroid patients.

OBJECTIVE: To try and resolve some of the problems associated with the treatment of goitre in euthyroid patients. DESIGN: Retrospective open study SETTING: University hospital SUBJECTS: 106 out of a total of 161 euthyroid patients operated on for goitre from 1974-1988. Those who underwent total thyroidectomy (n = 14), in whom the histological diagnosis was thyroiditis (n = 10), or who were lost to follow up (n = 31) were excluded from the study. MAIN OUTCOME MEASURES: Recurrence of goitre, and correlation with type of operation, age, and histological type. RESULTS: 62 Patients underwent unilateral, and 44 bilateral resections. There were 24 recurrences (23%), 13 of which were subclinical; 19 occurred after unilateral, and 5 after bilateral, resections (p = 0.02). There were no significant associations between recurrence and age or histological type. CONCLUSION: Subtotal thyroidectomy is the treatment of choice for goitre in euthyroid patients.