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Diagnostic endoscopy of the upper gastrointestinal tract is a safe procedure, which, however, is not without complications. We report the rare occurrence of retroperitoneal, mediastinal and subcutaneous emphysema following routine endoscopy, with no obvious evidence of a site of perforation. Possible etiological aspects are discussed. This complication appeared to be a benign clinical condition that was resolved with conservative, nonsurgical treatment.

Objective To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST). Material and Methods Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events. Results Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63–1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events. Conclusions Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy., Highlights • The prognostic impact of pCR after primary systemic therapy on DFS and OS has been shown in meta-analyses of randomized phase III trials. • The association of treatment response with loco-regional recurrence has been studied only in retrospective reports. • RNI should be strongly considered in patients with clinically involved lymph nodes regardless of the response to primary systemic therapy, especially in the presence of further risk factors. • In patients with cN2 at diagnosis and ypN0 at surgery after PST, loco-regional RT should be evaluated for each patient in the multidisciplinary team.

Purpose: To perform a systematic review of the current level of evidence on post-operative management following brain metastasectomy (namely: adjuvant stereotactic radiosurgery, whole brain radiotherapy or observation), and to propose a GRADE-based dedicated recommendation to inform Radiation Oncologists’ clinical practice. Methods: A panel of expert Radiation Oncologists from the Italian Association of Radiotherapy and Clinical Oncology had defined the search question per the PICO methodology. Electronic databases were independently screened; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was adopted. The individual and pooled hazard ratios with 95% confidence intervals (CI), as well as the pooled risk ratio (RR) were calculated using a fixed- or random-effects model. Results: Eight full-texts were retrieved: six retrospective studies and two randomized clinical trials. Outcomes of benefit and damage were analyzed for SRS + observation (PICO A) and SRS + WBRT. SRS allowed for increased rates of local control when compared to both observation and WBRT, while evidence was less conclusive for distant brain control, leptomeningeal disease control and overall survival. In the SRS, the incidence of severe radionecrosis was higher as compared to WBRT, despite neurocognitive deterioration rates were lower. Overall, SRS seems to favorably compare with observation and whole brain RT, despite the level of evidence for the recommendation was low and very low, respectively. Conclusion: Despite low level of evidence, the panel concluded that the risk/benefit ratio probably favors adjuvant SRS as compared to the observation and whole brain RT as adjuvant treatments following brain metastasectomy (5 votes/5 participants, 100% attendance).

Background: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated. Methods: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity. Results: Locoregional control was improved by EBRT while no considerable toxicity impact was reported. Conclusion: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.

Introduction: Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. Aims: A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC Materials and methods: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3–G4 toxicity, late pulmonary toxicity G3–G4, and acute esophageal toxicity G3–G4. Results: The probability of OS and G3–G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. Conclusions: The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.

Purpose To evaluate efficacy and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy and identify differences in clinical outcomes and severe toxicity rate. Methods PICOS/PRISMA methods were used to identify studies on PubMed, EMBASE and Cochrane Library, 2005–2019. Results Six randomized clinical trials (554 patients) were identified. Weekly cisplatin was not associated with significant overall survival (HR 1.13, 95 % CI 0.84–1.51) and progression-free survival (HR 1.23, 95 %CI 0.91–1.65) improvement compared with three-weekly regimen. Severe acute toxicity (RR 0.95), treatment compliance to chemotherapy (RR 1.67) and radiotherapy (RR 0.61) were similar between regimens. Conclusion Weekly cisplatin is not associated with better clinical outcomes compared to three-weekly cisplatin. Three-weekly cisplatin chemoradiotherapy should be considered the standard approach in the management of locally advanced head and neck cancer. Methodologically robust RCTs designs are needed to improve the quality of evidence. Differences on long-term toxicity and cost-effectiveness remain to be tested.

Background: The availability of a number of agents that are efficacious in patients with metastatic prostate cancer (mPC) has led to them being used sequentially, and this has prolonged patient survival. However, in order to maximize their efficacy, clinicians need to be able to obtain a reliable picture of disease evolution by means of monitoring procedures. Methods: As the intensive monitoring protocols used in pivotal trials cannot be adopted in everyday clinical practice and there is no agreement among the available guidelines, a multidisciplinary panel of Italian experts met to develop recommendations for monitoring mPC patients using a modified Delphi method. Results: The consensus project considered methods of clinically, radiographically, and biochemically monitoring patients with metastatic hormone-sensitive and metastatic castration-resistant prostate cancer undergoing chemotherapy and/or hormonal treatment. The panelists also considered the methods and timing of monitoring castration levels, bone health, and the metabolic syndrome during androgen deprivation therapy. Conclusions: The recommendations, which were drawn up by experts following a formal and validated consensus procedure, will help clinicians face the everyday challenges of monitoring metastatic prostate cancer patients.

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.

Aim To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC). Material and Methods Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made. Results Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72–77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC. Conclusions TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery.

Background: The aim of this study was to record the opinions of Italian oncologists about the use of oral vinorelbine administered metronomically in patients with advanced breast cancer. Methods: A series of meetings were held throughout Italy, and participants were asked how much they agreed with each of the several statements. Results: The majority of oncologists agreed that the concept of the minimum biologically effective dose should be used for drugs administered metronomically. Over 50% agreed that metronomic vinorelbine is an option in first-line chemotherapy for patients with advanced breast cancer, including those with a terminal illness and the elderly, as well as in young and fit patients. Just over one-third of experts agreed that a combination of two chemotherapy agents instead of one is not desirable in metastatic breast cancer because of increased toxicity. Most experts agreed that the main aim of a first-line therapy is to control the disease over time and to preserve quality of life. Conclusion: Metronomically administered oral vinorelbine, either as monotherapy or in combination with other drugs, is effective in the long-term treatment of patients with advanced breast cancer. The clinical profiles of patients should be carefully considered to determine the appropriate treatment strategy.

PURPOSE: Bacillus Calmette-Guérin and intravesical chemotherapy represent viable adjuvant options for intermediate risk nonmuscle invasive bladder cancer. Although bacillus Calmette-Guérin is perceived as less tolerable than intravesical chemotherapy, to our knowledge no comparative studies have addressed quality of life issues. We compared the quality of life of patients with nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine or 1/3 dose bacillus Calmette-Guérin. MATERIALS AND METHODS: Our multicenter, prospective, randomized, phase II study included 120 patients with intermediate risk nonmuscle invasive bladder cancer. Of these patients 88 remained assessable at 1-year followup. Only 1 patient was withdrawn because of adverse events. Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks (maintenance monthly for 1 year) while 59 received 1/3 dose bacillus Calmette-Guérin Connaught weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6 and 12 months). Quality of life was measured by the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0) and QLQ-BLS24 (Quality of Life Superficial Bladder Cancer-Specific 24) questionnaires. Group differences were calculated using ANOVA (ANOVA/MANOVA). RESULTS: Treatment was well tolerated in both groups, although local and systemic side effects were more frequently reported in the bacillus Calmette-Guérin arm. Multivariate analyses showed no significant differences between the 2 groups in all quality of life dimensions. No significant changes over time in quality of life domains were detected for patients on bacillus Calmette-Guérin and gemcitabine except for physical functioning, which decreased significantly in both groups (p = 0.002). No significant differences were detected in terms of recurrence and progression between the 2 groups at 1-year followup. CONCLUSIONS: While a higher rate of side effects, albeit mild to moderate, was detected with 1/3 dose bacillus Calmette-Guérin compared to gemcitabine, our study failed to show significant differences between the 2 drugs in terms of quality of life.

To assess the existence of a vesical hypothalamic reflex by evaluating the changes of plasmatic ADH levels during acute bladder filling in healthy adult volunteers.Twenty normal male subjects aged between 19 and 40 years (average age 31.6 years) were evaluated. All subjects signed informed consent. The subjects had no pathologic blood and urine examination, no cardiovascular, hepatic, renal disease, they were no smokers and they did not take drugs which may interfere with plasmatic ADH levels. A blood sampling at rest condition (time 0) and successively during cystometry in the presence of first sensation, normal and strong desire was carried out. Plasmatic ADH was measured on extracted samples by radioimmunoassay. A one-factor repeated measures analysis of variance was employed to verify the effect of time on ADH levels. The Greenhouse-Geisser and Huynh-Feldt adjustments were adopted to protect against the case of violation of homogeneity of covariance.Statistical analysis did not show significant differences of plasmatic ADH levels between rest condition and bladder filling.We exclude the existence of a vesical hypothalamic reflex and we suppose that extravesical factors may interfere with the plasmatic ADH production during the night.

This study aims to define the usefulness of antibiotic prophylaxis of urinary tract infection (UTI) in postmenopausal female undergoing invasive urodynamics (IU). Two hundred sixty-two postmenopausal females underwent IU. Before urodynamics, all females were double blindly randomized in two age stratified groups. Group 1 (130 patients) received oral antibiotic prophylaxis with a single 400-mg dose of norfloxacin. Group 2 (132 patients) received norfloxacin placebo. Statistical analysis was performed by a chi (2) test to evaluate differences between groups for UTI incidence rate. Fifty-four patients of 262 (20.6%) resulted affected by UTI [24 of 130 subjects who received antibiotic prophylaxis (18.4%) and 30 of 132 subjects who received placebo (22.7%)]. There was no statically significant difference (P = 0.242) regarding UTI incidence rate between patients who received and those who did not received antibiotic prophylaxis. UTI incidence rate in postmenopausal women undergoing urodynamics is not affected by administration of antibiotic prophylaxis at the desired level of efficacy.

Elderly patients with nonoperable transitional cell carcinoma of the bladder need a rather active, but less toxic treatment than full-dose polychemotherapy. This study was designed to determine whether the cisplatin-analogue carboplatin (which is less nephrotoxic and less neurotoxic than the parent compound) has sufficient activity against T 2 -T 4 neoplasms (both nonmetastatic and metastatic) to warrant further development in phase III trials. Carboplatin dose was adjusted according to creatinine clearance, with a maximum dose of 300 mg/m 2 . The patient selection for this screening for activity was adjusted by the use of the 'optimal' two-stage design. Seventeen patients were enrolled, with a median age of 78 years (range : 70-85), a median performance status of 80% (range : 70-90%) ; 13 patients were lymph node-negative (10 T 2 , 2 T 3 , 1 T 4 ) and 4 had locoregional or distant node metastases. Nine patients had a complete response (3 in the first, 9-patient, stage, and 6 in the second, 8-patient, stage), demonstrating that carboplatin had sufficient activity (at the 'desirable' target level of 35%) ; almost all responses were observed in T 2 patients. Six patients had stable disease, and 2 had disease progression during treatment. The toxicity was acceptable, with only 41% of patients having grade II-III hematologic toxicity. More than 30% of patients were estimated to be free from progressive disease (54% alive) at 24 months. In our opinion carboplatin is suitable to be tested - in a phase III testing versus full-dose radiation therapy - as adjuvant after initial transurethral resection of the prostate in elderly patients with T 2 transitional cell carcinoma of the bladder considered radically nonoperable for medical problems.