Water vapor therapy (Rezum) for lower urinary tract symptoms related to benign prostatic hyperplasia: early results from the first Italian multicentric study.

PURPOSE: Rezum is the latest developed minimally invasive treatment for benign prostatic hyperplasia (BPH). We aimed to carefully assess the functional outcomes of patients treated with Rezum for BPH. METHODS: We prospectively followed 135 consecutive patients treated by Rezum at 5 institutions from June 2019 to August 2020. The International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF), the Overactive Bladder Questionnaire-Short Form (OAB-q SF) score, the International Index of Erectile Function (IIEF-5) and questions 9 and 10 to assess ejaculatory dysfunction were recorded. Election criteria were age > 18, no prior prostate interventions, IPSS ≥ 13, post-void residual ≤ 250 mL, prostate volume between 30 and 120 cc. RESULTS: The median operative time was 10.5 (IQR 8.7-15) min. All patients were dismissed few hours after surgery with indwelling urinary catheter that was removed after a median of 7 (IQR 7-10) days. A significantly decrease of IPSS from baseline at first (p = 0.001) and third (p < 0.0001) month after surgery was reported. No difference was reported in terms of ICIQ-UI SF score postoperatively. A mild reduction of the OAB-q SF score was reported at 1 month from surgery (p = 0.06) that turned significant at 3 months postoperatively (p < 0.0001). A slight but statistically significant increase of the IIEF-5 score was reported from baseline at 6 months (p = 0.04). Postoperatively, patients reported a significantly decrease of ejaculatory dysfunction after alpha-blocker interruption. CONCLUSION: Rezum treatment is a feasible minimally invasive option for patients with BPH symptoms and showed optimal early functional outcomes.

Phase II trial of a biweekly regimen of fluorouracil and leucovorin plus irinotecan in patients with previously untreated advanced gastric cancer.

To investigate the therapeutic value and safety of the biweekly regimen of 5-fluorouracil (5-FU) and leucovorin (LV) plus irinotecan (CPT-11) in patients with previously untreated advanced gastric cancer (AGC). A total of 50 patients (M/F 35/15; median age = 65) with AGC, none of whom had received chemotherapy for advanced disease, were accrued in this trial. Fifteen patients (30%) were 70 years old or older. At the time of their accrual, cytotoxic chemotherapy, consisting of LV 100 mg/m(2) (2-hour i.v. infusion) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22-hour continuous infusion) on therapeutic days 1 and 2 plus CPT-11 180 mg/m(2) (1-hour infusion) on day 1, was initiated. Treatment courses were repeated every 2 weeks until evidence of progressive disease, unacceptable toxicity or withdrawal of consent. All patients were assessable for toxicity and 48 of 50 for response evaluation, having completed at least four courses of chemotherapy. Complete response was achieved in 2 patients (4%, intent to treat) and partial response in 16 (32%) (overall response rate, 36%; 95% confidence interval [CI]: 22%-50%). Twenty-four patients (48%) had stable disease and 6 patients (16%) progressed. The median time to progression was 8 months (95% CI: 6-10 months) and median overall survival 14 months (95% CI: 6-22 months). Between the subgroups of patients <70 years old and 70 or older, there were no significant differences in efficacy. One toxic death occurred. Treatment tolerance was generally mild to moderate and easy to treat. The main grade 3/4 toxicities were neutropenia (32%), diarrhea (16%), and anemia (8%). Grade 3-4 neutropenia was the only treatment-related serious adverse event significantly more common in patients older than those aged <70 (53.3% vs 22.8%, respectively; P = 0.03). Our data suggest that the biweekly regimen of LV and 5-FU plus CPT-11 in untreated patients with AGC is active and has an acceptable safety profile. Further evaluation of this regimen seems to be warranted in a phase III trial.

[Clinical guidelines for the management of gastrointestinal stromal tumors]. / Raccomandazioni cliniche per la diagnosi, la terapia ed il follow-up dei tumori stromali gastrointestinali.

Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.

Our experience with nifedipine and prednisolone as expulsive therapy for ureteral stones.

OBJECTIVES: We evaluated the effect of nifedipine associated with prednisolone in ureteral stone passage. MATERIAL AND METHODS: In our department we enrolled 50 patients with radiopaque ureteral stones. Stone size was 15 mm or less. The patients were divided into two groups: group I included 25 patients who received 30 mg oral treatment of slow-release nifedipine (for a maximum of 20 days) and 25 mg of prednisolone (for a maximum of 10 days) daily. Group II was made up of 25 patients who received 25 mg of prednisolone daily. On request, both groups could use non-steroidal anti-inflammatory drugs. RESULTS: The mean expulsion time was 6 days in group I and 10 days in group II. The average stone size was 12 mm in group I and 12.8 mm in group II. Six patients suspended therapy in group I (5 erythema, 1 stomachache), and seven in group II (3 because of intolerable pain, 4 stomachache). The expulsion success rates were 68% in group I and 81% in group II. CONCLUSIONS: For ureteral stones that do not cause an emergency situation, such as obstructive uropathy, infection or intolerable pain, we suggest expulsive medical treatment with nifedipine and prednisolone, if there are no contraindications to drug use.

Role of Ca 15-3 in patients with biochemically suspected prostate cancer and multiple negative ultrasound-guided prostate biopsies.

Ca 15-3 is an aspecific tumor marker characteristic of cancer proliferation. Elevated serum levels seem to be closely correlated with cancer progression in non-urological tumors. This study assessed the role of Ca 15-3 as an aspecific tumor marker in patients with borderline prostate-specific antigen (PSA) biochemically suspected of prostate cancer (PCa) and with multiple negative prostate biopsies. The study is based on prospective analysis of 103 patients: (a) 33 patients (group A) presented lower urinary tract symptoms secondary to BPH with normal serum PSA values, DRE and TRUS negative for suspected PCa; (b) 31 patients (group B) with histologically diagnosed PCa; (c) 39 patients (group C) with borderline serum PSA values, DRE and TRUS normal, two ultrasound (US)-guided random prostate biopsies negative for PCa. Ca 15-3 was determined in the entire study series by the IRMA method, using as range the values proposed for the investigated non-urological tumors (38 UI/l).Ca 15-3 was within normal range in all group A patients (control), while the values were elevated in 27/31 of group B patients (PCa) and in 11/39 of group C (PCa suspected) patients. A third biopsy was performed in all 39 group C patients with borderline PSA and it was PCa-positive in 13 patients (33.3%, subgroup C3). In this series Ca 15-3 was increased in 9 of 13 patients (subgroup C3alpha), while the remaining four patients (subgroup C3beta) presented values within the normal range. On 26 group C patients who were negative for PCa to third biopsy (subgroup C4), 24 patients had Ca 15-3 levels within normal range (subgroup C4alpha) with histologic findings of BPH in 23 cases and granulomatous chronic prostatitis in one case, while two patients (subgroup C4beta) had elevated Ca 15-3 concentrations associated with lymphoplasmacytic chronic prostatitis. We hypothesize that Ca 15-3, as a specific tumor marker, could be an interesting and inexpensive second step diagnostic tool for PCa in patients with borderline PSA and multiple negative prostate biopsies, as it could indicate whether a repeated biopsy should be performed in a short time, having excluded other concomitant tumors. However, further prospective studies will be necessary to confirm this hypothesis.

[Percutaneous lithotripsy: how to make it safer. Personal experience]. / Litolapassi percutanea: come renderla più sicura. Nostra esperienza.

BACKGROUND: Percutaneous surgery (PCN) is now a routinary method for the treatment of the majority of renal stones, since it has become safer than in the past, because, thanks to new endourologic instruments and to ultrasounds, it has been possible to reduce the mistakes of the renal puncture. Furthermore, the use of balloons catheters for the dilatation of the nephrostomic channel allows the reduction of operating time and hemorrhage risk. In this paper, the authors expose their experience in PCN operations carried out with the help of X-ray and ultrasonography, during the indirect laying of the stones, and the use of a balloon catheter for the creation of a working channel. METHODS: The Authors report their experience with the use of ultrasounds and concomitant X-rays for renal puncture, and of balloon catheter as track dilator, during 68 consecutive PCN carried out for renal lithiasis, 55 primary and 13 secondary to ESWL treatments; every stone has been cracked by a "Swiss-lithoclast" balistic lithotripter. For every patient, time of operation, complications and hospitalization-days were registered. RESULTS: Only three patients (4.4%) had haemorrhages and in one case of A-V fistula nephrectomy was necessary. The patients stayed in hospital approx. four days; the nephrostomic drainage was generally removed 3 days after the operation. CONCLUSIONS: The very low incidence of complications and the very short time of hospitalization suggest that ultrasounds and balloon-catheters may be useful to this surgery and may make it safer than in the past. Moreover, ultrasonography reduces the rate of X-rays exposition for operators and patients; the cost of the balloon is easily balanced by the reduction of operating times and hospitalization-days.

Ventilation and pulmonary mechanics during high-frequency oscillation of immature lungs at birth.

Ventilation was initiated and maintained by high-frequency oscillation (HFO) in nine immature lambs not expected to survive for more than a few minutes out of the uterus. They were delivered to HFO (18 to 20 Hz) and ventilated only with air at the setting that yielded optimal blood gases and pH. Once removed from HFO, cardiorespiratory arrest occurred within minutes despite the return of previously inhibited natural inspiratory efforts. At autopsy, the lungs were liquid-filled (i.e., fetal). Thus, HFO had maintained viability without promoting either lung stability or fetal pulmonary fluid (FPF) absorption. Additional experiments on excised immature lungs showed that aeration is determined by distending pressure, which is regulated by the flow through the oscillator circuit and monitored most accurately as transpulmonary pressure (TPP). Once air-entry has begun, alveolar recruitment and negative compliance establish the limits of tolerable lung expansion via TPP. Within these limits, the immature lung can be ventilated effectively with air. However, since these lungs do not produce intrapulmonary foam, lung stability and FPF absorption are not effected. Complications of HFO (including pneumothorax, decreased arterial pressure and heart rate, and metabolic acidemia) can be related to overdistention of the lungs.

The progressive onset of spontaneous and induced fetal breathing.

Intratracheal pressure (ITPmax) and respiratory drive (dITP/dt) from the occluded, liquid-filled trachea of term fetal lambs in utero were measured for each breath at the onset of fetal breathing (1) during spontaneous breathing, (2) during sciatic nerve stimulation, (3) during induced hypercapnia, and (4) following naloxone administration. These responses were characterized by linear increase of ITPmax and dITP/dt following which these parameters became stable. The rate of rise of ITPmax and dITP/dt was lowest and similar during spontaneous breathing and sciatic stimulation, but increased incrementally with hypercapnia and naloxone. Mechanical factors could not account for these responses in the liquid-filled lung, nor did appreciable chemical changes occur during this period. These results suggest that progressive breathing responses at the onset of fetal breathing may stem from gradual recruitment of central respiratory neurons, and that the rate of rise of such recruitment depends on facilitation by natural arousal, somatosensory stimulation and hypercapnia as well as on release from natural endorphin inhibition.

Cutaneous stimulation and generation of breathing in the fetus.

The generation of spontaneous regular breathing by cutaneous stimulation and by direct electrical stimulation of the sciatic nerve was examined in six previously apneic mature fetal lambs in utero. The fetuses were stable throughout the course of the experiments: PaO2 less than or equal to 27 mm Hg, PaCO2 less than 44 mm Hg, pH 7.29-7.34, blood pressure and heart rate steady and normal. It is shown that electrical stimulation of the fetal skin (66 cps, 4.0 msec, 6 V, 0.77 ma) can be as effective as direct stimulation of the sciatic nerve (66 cps, 4.0 msec, 1.5 V, 0.08 ma) when the higher voltage and current are used. Mechanical cutaneous stimulation also produced spontaneous breathing which, however, was short lived compared with that produced by electrical stimuli. The results are consonant with our concept of activation and recruitment of quiescent respiratory center neurones by somatic sensory stimulation, and they give fundamental support to the clinical observation of others that cutaneous stimulation is effective for the treatment of apnea of prematurity. Speculation Somatic sensory stimuli from the skin may be important determinants of the onset of breathing in the fetus and newborn.

Fetal breathing: induction in utero and effects of vagotomy and barbiturates.

Breathing movements were induced in the mature fetal lamb in utero by (1) both electrical stimulation and manipulation of the sciatic nerve, (2) stimulation of cutaneous receptors, and (3) KCI injection into the peripheral circulation. The breathing patterns that were produced included the "respiratory reflex", sustained regular breathing lasting up to three hours, and short bursts of irregular breathing. The latter resembled the spontaneous irregular breathing of the fetus in situ as reported by others. It is suggested that the intensity of peripheral somatic stimulation is an important determinant of the resultant breathing activity, ie, low intensity produces irregular breathing and high intensity, sustained regular breathing. The breathing responses were not affected by bilateral cervical vagotomy, but were inhibited completely by maternal administration of pentobarbital and of quantities of thiopental and methohexital equal to or less than the doses used clinically.

Somatic-respiratory reflex and onset of regular breathing movements in the lamb fetus in utero.

Breathing activity of six mature lamb fetuses (greater than 135 days of gestation) in utero was monitored from recordings of intraesophageal pressure, intratracheal pressure, and tracheal circumference from a mercury strain gauge before, during, and after stimulation of the central end of a cut sciatic nerve. Stimuli were either low (0.5-2.0 cps) or high (66 cps) frequency, 6-15-V square wave pulses of 0.6-1.25 msec duration. The fetuses remained in utero throughout the experiments in which ambient temperature, paO2, paCO2, arterial pH, mechanical stimulation, and spontaneous respiratory center activity could be ruled out as primary stimuli of the breathing movements observed. In one-third of the trials a "somatic-respiratory reflex" was elicited in which breathing coincided with the period of stimulation: in over 85% of these trials with low frequency stimulation, breathing movements were synchronous with the stimuli; in the rest the synchrony was broken during the period of stimulation. In two-thirds of the trials the "reflex" response was followed by spontaneous regular breathing movements ("onset of regular breathing") which continued for 1 min to 2 hr 30 min after the stimulation was stopped. Thiopental administration to the ewe (5 mg/kg) seemed to depress respiratory responsivity for about 60 min. Changes of tracheal circumference reflected both transmural pressure gradients and possibly also rhythmic vagal activity associated with breathing.

Lamb fetal pulmonary fluid. I. Validation and significance of method for determination of volume and volume change.

An indicator-dilution method is described for measuring fetal pulmonary fluid, FPF, volume (Ve), and volume change with time (Vs) in the lamb fetus in utero. The indicator, albumin, which is the predominant protein of normal FPF, was administered directly to FPF in the form of radio-iodinated human serum albumin (RISA). We have shown that (1) RISA is distributed homogeneously throughout the FPF compartment, (2) it is not altered within FPF, (3) it does not alter the functional characteristics of FPF, and (4) it remains within the FPF compartment throughout the period of measurement. Ve varies directly with the weight of the fetus so that Ve per kilogram was 31.6-35.6 ml/kg in four of five fetuses. The Ve per kilogram was lower in one fetus at the start of the experiment but increased rapidly to 29.0 ml/kg within 45 min. Thus the relaxation volume of the fetus in utero is in the range of functional residual capacity (FRC) and thoracic gas volume of the air-breathing neonate, which indicates that the pulmonary transformation at birth is, in essence, an isovolumic change in state wherein the fetal liquid-lung becomes the neonatal air-lung. The rate at which FPF is formed (Vs) is about 1.5 ml/hr-kg; however, the rate may change in so far as both rapid increases and rapid decreases of FPF volume were observed. When breathing movements were induced in the fetus by stimulation of the sciatic nerve, FPF volume decreased rapidly (Vs equals -3.0 ml/hr-kg), which indicates that negative intrathoracic pressures promote its resorption. When FPF volume fell transiently or was low initially, there was subsequent rapid restoration of volume to the range of anticipated FRC.

Lamb fetal pulmonary fluid. II. Fate of phosphatidylcholine.

Using the radio-iodinated human serum albumin ([131-I]-RISA) dilution method to measure lamb fetal pulmonary fluid (FPF) volume, we followed the disappearance of protein-complexed, 14-C-labeled phosphatidylcholine ([14-C]PC) during the first 90 min after its injection into FPF. The FPF samples were analyzed for total lipid 14-C activity and for distribution of 14-C in PC, other phospholipids (PL), fatty acids (FA), and neutral lipids (NL). For most sampling periods ascending aortic (AAo) and right atrial (RA) blood samples were obtained simultaneously with FPF and serum was analyzed for total lipid 14-C activity and for distribution of 14-C in total PL, FA, and NL. These studies indicate that (1) PC is cleared rapidly from FPF with an estimated half-time of 15-57 min; (2) FPF-PC may be metabolized to lyso-PC and FA within the fluid itself; and (3) FA derived from PFP-PC enter the pulmonary circulation, thus establishing a pulmonary arteriovenous FA gradient. The possible sites at which PC may be cleared from FPF are considered.