Search

Background: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. Objectives: This study aimed to evaluate health‐related quality of life (HRQoL) in melanoma patients pre−/post‐ECT and its effect on treatment outcome. Methods: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15 000 IU/m2; 1000 IU mL/cm3) followed by 100‐microsecond, 1000‐V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression‐free survival (LPFS), toxicity (CTCAE v5.0), and patient‐reported HRQoL at baseline, one, two, four, and 10 months (EuroQol [EQ‐5D‐3L], including 5‐item utility score [EQ‐5D] and visual analogue scale for self‐reported health state [EQ‐VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. Results: Median tumour size was 2 cm. Complete response rate, G3 toxicity, and one‐year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%, respectively. At baseline, age‐paired HRQoL did not differ from the general European population. Following ECT, both EQ‐5D and EQ‐VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ‐5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within 4 months), and self‐care and usual activities (throughout the follow‐up) domains. Concomitant checkpoint inhibition correlated with better EQ‐5D and EQ‐VAS trajectories. Baseline EQ‐5D was the exclusive independent predictor for complete response (RR 14.76, P = 0.001). Conclusions: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self‐care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information, which can help identify patients most likely to respond. [ABSTRACT FROM AUTHOR]

Background: This study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM)., Methods: We audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006-2020) within the International Network for Sharing Practices of ECT (InspECT)., Results: 452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1-8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years., Conclusions: Among patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support., Competing Interests: Declaration of competing interest LGC, JO, MM, JAC, EK, MB, RC, AM, HS, and GS received travel grants unrelated to this work from Igea Clinical Biophysics S.p.A. (Carpi, Italy). FT, JB, SC, GC, VF, DP, KB, KB, SS, MB, FF, PC, LS, CC, TF, KE, LB, and SV have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck. A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe. Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65 %, with a 33 % complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent. This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent., Competing Interests: Declaration of competing interest Francesca de Terlizzi is an IGEA employer. No other authors have conflicts of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Severe and/or symptomatic hypocalcemia due to hypoparathyroidism is the main contraindication for discharge in patients who have undergone thyroid surgery. Hypomagnesemia may contribute to the onset of hypoparathyroidism and is frequently observed after thyroid surgery in hypocalcemic patients. The impact of prophylactic and postoperative Magnesium supplementation on postoperative hypocalcemia and hypomagnesemia was prospectively evaluated by comparing patients undergoing prophylactic supplementation to a control group of patients who had only received magnesium after evidence of postoperative hypomagnesemia., Methods: One hundred and twenty patients who underwent a total thyroidectomy participated in the study. Seventy-three patients were included in the study group, 47 in the control group. Prior to surgery, patients in the study group were given magnesium orally for 5 days; postoperatively, calcium and magnesium was administered to all patients who displayed hypocalcemia and hypomagnesemia., Results: Postoperative biochemical hypocalcemia (serum calcium <8.5 mg/dL, regardless of its clinical severity) was found in 60 patients (50%) on D1 and in 58 patients (48.4%) on D2. Among hypocalcemic patients, hypomagnesemia was recorded in 29 at D1 (48%), and in 46 at D2 (79%). A significant positive correlation was found between magnesium, calcium, and parathyroid hormone in the first two postoperative days, while a significant inverse correlation occurred for these same parameters and length of hospital stay (P<0.001). One hundred and five patients (87.5%) were discharged as expected on the second postoperative day (65 in the study group, 40 in the control group, P=0.724), whereas 15 patients (12.5%) required prolonged hospitalization (eight in the study group, seven in the control group, P=0.721). The Study group only showed significantly higher magnesium levels on the first postoperative day (P=0.03)., Conclusions: Although magnesium and calcium levels showed the same trend after thyroidectomy, neither Magnesium prophylaxis nor Magnesium treatment influenced the clinical course of postoperative hypocalcemia.

Background: Due to delayed diagnosis and a lower surgical indication rate, left-sided pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis in comparison to pancreatic head tumors. Multi-visceral resections (MVR) associated with distal pancreatectomy could be proposed for patients presenting with locally infiltrating disease., Methods: We retrospectively analyzed a multi-centric cohort of left-sided PDAC patients operated on from 2009 to 2020. Thirteen European high-volume HPB centers participated in this study. We analyzed patients who underwent distal pancreatectomy (DP) associated with MVR and compared them to standard DP patients., Results: Among 258 patients treated curatively for PDAC of the body and tail, 28 patients successfully underwent MVR. A longer operative time was observed in the MVR group (295 min +/- 74 vs. 250 min +/- 96, p= 0.248). The post-operative complication rate was comparable between the two groups (46.4% in the MVR group vs. 62.2% in the control group, p= 0.108). The incidence of positive margin (R1) was similar between the two groups (28.6% vs. 26.6%; p=0.827). After a median follow-up of 25 (9-111) months, overall survival was comparable between the two groups (p= 0.519)., Conclusions: Multi-visceral resection in left-sided pancreatic ductal adenocarcinoma is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ ( p = 0.0297) and HR+ ( p = 0.0094), while overall survival was affected by time to local progression in all groups ( p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions.

Although several studies have explored the molecular landscape of metastatic melanoma, the genetic determinants of therapy resistance are still largely unknown. Here, we aimed to determine the contribution of whole-exome sequencing and circulating free DNA (cfDNA) analysis in predicting response to therapy in a consecutive real-world cohort of 36 patients, undergoing fresh tissue biopsy and followed during treatment. Although the underpowered sample size limited statistical analysis, samples from non-responders had higher copy number variations and mutations in melanoma driver genes compared to responders in the BRAF V600+ subset. In the BRAF V600- subset, Tumor Mutational Burden (TMB) was twice that in responders vs. non-responders. Genomic layout revealed commonly known and novel potential intrinsic/acquired resistance driver gene variants. Among these, RAC1 , FBXW7 , GNAQ mutations, and BRAF / PTEN amplification/deletion were present in 42% and 67% of patients, respectively. Both Loss of Heterozygosity (LOH) load and tumor ploidy were inversely associated with TMB. In immunotherapy-treated patients, samples from responders showed higher TMB and lower LOH and were more frequently diploid compared to non-responders. Secondary germline testing and cfDNA analysis proved their efficacy in finding germline predisposing variants carriers (8.3%) and following dynamic changes during treatment as a surrogate of tissue biopsy, respectively.

Background/aim: Rectal cancer (RC) represents 30% of colon cancers. Despite the progress achieved in integrated chemoradiotherapy and surgical multidisciplinary treatments, the rate of local recurrence (LR) is 3.7-13%. Multivisceral resections allow many patients with pelvic recurrence to be treated in a curative manner. The purpose of this work is to assess the impact of surgery for rectal cancer patients with pelvic recurrence., Patients and Methods: In a retrospective study from 2013 to 2018, data was collected from patients who had undergone rectal resection for adenocarcinoma. We compared perioperative data, postoperative outcomes, oncological results, and survival rates., Results: 106 rectal cancer patients (40-87 years old) requiring surgery were included. The local recurrence rate was 15% (15 patients). LR patients requiring intervention were nine (56%) who underwent sphincter sparing surgeries, and 6 (44%) who underwent surgeries with sphincter resection. There was no statistically significant difference (p=0.416) in the 5-year overall survival rate of patients without recurrence compared to those with pelvic recurrence., Conclusion: Curative surgery for local recurrence from rectal cancer is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Metastatic uveal melanoma (MUM) is a highly aggressive, therapy-resistant disease. Driver mutations in Gα-proteins GNAQ and GNA11 activate MAP-kinase and YAP/TAZ pathways of oncogenic signalling. MAP-kinase and MEK-inhibitors do not significantly block MUM progression, likely due to persisting YAP/TAZ signalling. Statins inhibit YAP/TAZ activation by blocking the mevalonate pathway, geranyl-geranylation, and subcellular localisation of the Rho-GTPase. We investigated drugs that affect the YAP/TAZ pathway, valproic acid, verteporfin and statins, in combination with MEK-inhibitor trametinib., Methods: We established IC50 values of the individual drugs and monitored the effects of their combinations in terms of proliferation. We selected trametinib and cerivastatin for evaluation of cell cycle and apoptosis. Synergism was detected using isobologram and Chou-Talalay analyses. The most synergistic combination was tested in vivo., Results: Synergistic concentrations of trametinib and cerivastatin induced a massive arrest of proliferation and cell cycle and enhanced apoptosis, particularly in the monosomic, BAP1 -mutated UPMM3 cell line. The combined treatment reduced ERK and AKT phosphorylation, increased the inactive, cytoplasmatic form of YAP and significantly impaired the growth of UM cells with monosomy of chromosome 3 in NSG mice., Conclusion: Statins can potentiate the efficacy of MEK inhibitors in the therapy of UM.

The success of mass vaccination programs against SARS-CoV-2 hinges on the public's acceptance of the vaccines. During a vaccine roll-out, individuals have limited information about the potential side-effects and benefits. Given the public health concern of the COVID pandemic, providing appropriate information fast matters for the success of the campaign. In this paper, time-trends in vaccine hesitancy were examined using a sample of 35,390 respondents from the Eurofound's Living, Working and COVID-19 (LWC) data collected between 12 February and 28 March 2021 across 28 European countries. The data cover the initial stage of the vaccine roll-out. We exploit the fact that during this period, news about rare cases of blood clots with low blood platelets were potentially linked to the Oxford/AstraZeneca vaccine (or Vaxzeveria). Multivariate regression models were used to analyze i) vaccine hesitancy trends, and whether any trend-change was associated with the link between the AstraZeneca vaccine ii) and blood clots (AstraZeneca controversy), and iii) the suspension among several European countries. Our estimates show that vaccine hesitancy increased over the early stage of the vaccine roll-out (0·002, 95% CI: [0·002 to 0·003]), a positive shift took place in the likelihood of hesitancy following the controversy (0·230, 95% CI: [0·157 to 0·302]), with the trend subsequently turning negative (-0·007, 95% CI: [-0·010 to -0·005]). Countries deciding to suspend the AstraZeneca vaccine experienced an increase in vaccine hesitancy after the suspensions (0·068, 95% CI: [0·04 to 0·095]). Trust in institutions is negatively associated with vaccine hesitancy. The results suggest that SARS-CoV-2 vaccine hesitancy increased steadily since the beginning of the vaccine roll-out and the AstraZeneca controversy and its suspension, made modest (though significant) contributions to increased hesitancy., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC., Materials and Methods: Patients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures., Results: The analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%)., Conclusion: In the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration., Competing Interests: FT is an IGEA employer. The remaining 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 © 2022 Bertino, Groselj, Campana, Kunte, Schepler, Gehl, Muir, Clover, Quaglino, Kis, Mascherini, Bisase, Pecorari, Bechara, Matteucci, Odili, Russano, Orlando, Pritchard-Jones, Moir, Mowatt, Silvestri, Seccia, Saxinger, de Terlizzi and Sersa.)

This study assesses how the implementation and lifting of non-pharmaceutical policy interventions (NPIs), deployed by most governments, to curb the COVID-19 pandemic, were associated with individuals' mental well-being (MWB) across 28 European countries. This is done both for the general population and across key-groups. We analyze longitudinal data for 15,147 respondents from three waves of the Eurofound-"Living, Working and COVID-19" survey, covering the period April 2020-March 2021. MWB is measured by the WHO-5 index. Our evidence suggests that restriction on international travel, private gatherings, and contact tracing (workplace closures) were negatively (positively) associated with MWB by about, respectively, -0.63 [95% CI: -0.79 to -0.47], -0.24 [95% CI: -0.38 to -0.10], and -0.22 [95% CI: -0.36 to -0.08] (0.29 [95% CI: 0.11 to 0.48]) points. These results correspond to -3.9%, -1.5%, and -1.4% (+1.8%) changes compared to pre-pandemic levels. However, these findings mask important group-differences. Women compared to men fared worse under stay-at-home requirements, internal movement restrictions, private gatherings restrictions, public events cancellation, school closures, and workplace closures. Those residing with children below 12, compared to those who do not, fared worse under public events cancellation, school closures and workplace closures. Conversely, those living with children 12-17, compared to those who do not, fared better under internal movement restrictions and public events cancelling. Western-Europeans vis-à-vis Eastern-Europeans fared better under NPIs limiting their mobility and easing their debts, whereas they fared worse under health-related NPIs. This study provides timely evidence of the rise in inequalities during the COVID-19 pandemic and offers strategies for mitigating them., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Electrochemotherapy (ECT) is an effective local treatment for cutaneous tumors. The aim of this study was to compare the effectiveness of ECT in ulcerated vs. non-ulcerated tumors and investigate the effect on tumor-associated symptoms., Methods: Twenty cancer centers in the International Network for Sharing Practices on Electrochemotherapy (InspECT) prospectively collected data. ECT was performed following ESOPE protocol. Response was evaluated by lesion size development. Pain, symptoms, performance status (ECOG-Index) and health status (EQ-5D questionnaire) were evaluated., Results: 716 patients with ulcerated (n = 302) and non-ulcerated (n = 414) cutaneous tumors and metastases were included (minimum follow-up of 45 days). Non-ulcerated lesions responded to ECT better than ulcerated lesions (complete response 65 % vs. 51 %, p = 0.0061). Only 38 % (115/302) with ulcerated lesions before ECT presented with ulcerated lesions at final follow-up. Patients with ulcerated lesions reported higher pain and more severe symptoms compared to non-ulcerated lesions, which significantly and continuously improved following ECT. In non-ulcerated lesions however, pain spiked during the treatment. No serious adverse events were reported., Conclusions: ECT is a safe and effective local treatment for cutaneous tumors. While ECT improves symptoms especially in patients with ulcerated lesions, data suggest the implementation of a perioperative pain management in non-ulcerated lesions during ECT., (© 2022 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Hintergrund: Elektrochemotherapie (ECT) ist eine wirksame lokale Behandlung von Hauttumoren. Ziel dieser Studie war es, die Wirksamkeit der ECT bei ulzerierten gegenüber nichtulzerierten Tumoren zu vergleichen und den Effekt auf tumorassoziierte Symptome zu untersuchen., Methodik: 20 Krebszentren des International Network for Sharing Practices on Electrochemotherapy (InspECT) sammelten prospektiv Daten. Die ECT wurde nach dem ESOPE-Protokoll durchgeführt. Das Therapieansprechen wurde anhand der Entwicklung der Läsionsgröße bewertet. Zusätzlich wurden Schmerzen, Symptome, Leistungsstatus (ECOG-Index) und Gesundheitszustand (EQ-5D-Fragebogen) untersucht., Ergebnisse: 716 Patienten mit ulzerierten (n = 302) und nichtulzerierten (n = 414) Hauttumoren und Metastasen wurden eingeschlossen (Mindest-Nachsorge 45 Tage). Nicht-ulzerierte Läsionen sprachen besser auf die ECT an als ulzerierte Läsionen (vollständiges Ansprechen: 65 % gegenüber 51 %, p = 0,0061). Nur 38 % (115/302) der Patienten mit ulzerierten Läsionen vor der ECT wiesen bei der letzten Nachuntersuchung ulzerierte Läsionen auf. Patienten mit ulzerierten Läsionen berichteten über stärkere Schmerzen und schwerere Symptome im Vergleich zu Patienten mit nichtulzerierten Läsionen, die sich nach der ECT signifikant und kontinuierlich besserten. Bei Patienten mit nichtulzerierten Läsionen hingegen nahmen die Schmerzen während der Behandlung vorübergehend zu. Es wurden keine schwerwiegenden Nebenwirkungen beobachtet., Schlussfolgerungen: Die ECT ist eine sichere und wirksame lokale Behandlung von Hauttumoren. Während die ECT die Symptome insbesondere bei Patienten mit ulzerierten Läsionen verbessert, sollte auf Basis der Daten die Implementation eines perioperativen Schmerzmanagements besonders bei nichtulzerierten Läsionen während der ECT erwogen werden., (© 2022 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Vaccine hesitancy can hinder the successful roll-out of vaccines. This paper examines COVID-19 vaccine hesitancy in the European Union, drawing from a large-scale cross-national survey covering all 27 EU Member States, carried out between February and March 2021 (n = 29,755). We study the determinants of vaccine hesitancy, focusing on the role of social media use. In multivariate regression models, we find statistically significant (p < 0.05) impacts on vaccine hesitancy of heavy use of social media and using social media as a main source of news. However, the effect of social media and the drivers of vaccine hesitancy vary depending on the reason for hesitancy. Most notably, hesitancy due to health concerns is mainly driven by physical health status and less by social media use, while views that COVID-19 risks are exaggerated (or that COVID-19 does not exist) are more common among men, people in good health, and those using social media as their main source of news., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC-IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% ( p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively ( p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively ( p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.

Background: With extending life expectancy, more people are diagnosed with cutaneous malignancies at advanced ages and are offered nonsurgical treatment. We assessed outcomes of the oldest-old adults after electrochemotherapy (ECT)., Methods: The International Network for Sharing Practices of ECT (InspECT) registry was queried for adults aged ≥90 years (ys) with skin cancers/cutaneous metastases of any histotype who underwent bleomycin-ECT (2006-2019). These were subanalysed with patients aged <90 ys after matching 1:2 for tumor location, number, size, histotype, and previous treatments. We assessed ECT modalities, toxicity (CTCAE), response (RECIST), and patient perception (EQ-5D)., Results: Sixty-one patients represented the study cohort (median 92 ys, range 92-104), 122 the control group (median 77 ys, range 23-89). Among the oldest-old, 44 patients (72%) had primary/recurrent skin cancers, 17 (28%) cutaneous metastases. Median tumour size was 15 mm (range, 5-450). The oldest-old adults underwent ECT mainly under local/regional anaesthesia (59% vs 39% p = .012). We observed no differences regarding dose and route of chemotherapy (intravenous vs intratumoral, p = .308), electrode geometry (linear vs hexagonal, p = .172) and procedural duration (18 vs 21 min, p = .378). Complete response (57.4 [95%-CI 44.1%-70.0%] vs 64.7% [95%-CI 55.6%-73.2%], p = .222) and 1-year local control (76.7% vs 81.7, p = .092) rates were comparable. Pain and skin hyperpigmentation were mild in both groups. Skin ulceration persisted longer in the oldest-old patients (4.4 vs 2.4 months, p = .008)., Conclusions: The oldest-old adults with cutaneous malignancies undergo ECT most commonly under local/regional anaesthesia with safety profiles and clinical effectiveness similar to their younger counterparts, except in case of ulcerated tumors., Competing Interests: Declaration of competing interest GS, MM, JO, JG, GB, BB, PC, EK, VL, TM, AO, RPJ, PQ, JPC, PM, and LGC received travel grants from IGEA S.p.A. (Carpi, Italy) to attend the annual InspECT meeting. FdT is IGEA S.p.A. employee. IGEA S.p.A. hosts the InspECT database, which is administered by an independent board; IGEA did not take part in study design, data collection and interpretation, and manuscript preparation. GAGM, CDP, RS, RC, and SV have no competing interests to declare., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Unpaid work carried out inside the home has increased in the pandemic, and evidence points to women's share in care responsibilities and domestic tasks remaining higher than those of men in the pandemic, continuing the gender divides of past decades., (© The Author(s) 2021.)

Background and Objectives: The purpose of the investigation was to compare clinical results and diagnostic accuracy for conventional multiport laparoscopic lymph node biopsy (MPLB) and single-port laparoscopic lymph node biopsy (SPLB) operations at a single institution., Methods: A set of 20 SPLB patients operated on from October 2016 to May 2019 were compared to an historical series of 35 MPLB patients. Primary endpoints were the time of surgery, estimated blood loss, surgical conversion, length of stay and morbidity. The secondary endpoint was the diagnostic accuracy of the technique., Results: SPLB was completed laparoscopically in all cases. Two MPLB patients (5.7%) experienced a surgical conversion due to intraoperative difficulties. Duration of surgery was similar in SPLB and MPLB groups respectively (84 ± 31.7 min vs. 81.1 ± 22.2; P = .455). A shorter duration of hospital stay was shown for patients operated on by SPLB compared to the MPLB group (1.7 ± 0.9 days vs. 2.1 ± 1.2 days; P  =   .133). The postoperative course was uneventful in both groups. In 95% of the SPLB and 97.1% of the MPLB cases respectively, LLB achieved the necessary information for the diagnosis., Conclusion: SPLB has shown good procedural and postoperative outcomes as well as a high diagnostic yield, comparable to traditional MPLB. Therefore, our results show that this approach is safe and effective and can be an equally valid option to MPLB to obtain a diagnosis or to follow the progression of a lymphoproliferative disease. Further studies are necessary to support these results before its widespread adoption., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest., (© 2020 by JSLS, Journal of the Society of Laparoscopic & Robotic Surgeons.)

Background/aim: Leiomyosarcoma is an extremely rare, small bowel neoplasm (2% of all gastrointestinal tumours). Early diagnosis is challenging due to the slow growth of the cancer. The biological behaviour of this group of tumours is aggressive, and the first-line treatment is surgical resection., Patients and Methods: This is a report of 4 cases of small bowel leiomyosarcoma that were treated in the last ten years at Hospital San Martino: one involving the jejunum and three involving the ileum (age range=69-86 years). Three patients underwent surgical resection and one was treated with chemotherapy., Results: All patients who were eligible for surgery underwent radical resection with R0 margins. Mean overall survival was 33 months (range=8-84 months)., Conclusion: Specific guidelines for small bowel leiomyosarcoma do not currently exist and these rare cases should be discussed in a multidisciplinary context. The first treatment approach is surgery, and in some cases, multivisceral resection may be needed to obtain free margins, even in recurrent cases., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction : In recent years, the introduction of targeted therapy and immunotherapy into clinical practice has radically changed the management of advanced melanoma. More recently, these treatments also became the standard of care in the adjuvant setting. However, high-risk resectable stage III melanoma (i.e. with clinically detected regional lymph node involvement and/or satellites/in transit metastases) still has a high risk of relapse, even after adjuvant treatment, suggesting that the activity of immunotherapy and targeted therapy may play a relevant role in a neoadjuvant setting. Area covered : In this review, we discuss the results of the main clinical trials conducted in the neoadjuvant setting for patients with resectable stage III and stage IV melanoma, with a focus on the hot topics and a look at the future perspectives of the field. Expert opinion : The long-term effects of immunotherapy and the high response rate of targeted therapy provided the strong rationale to start neoadjuvant clinical trials for patients with resectable stage III and oligometastatic stage IV melanoma. Neoadjuvant therapy may play an important role not only for its possible impact on overall survival, but also as a predictive biological marker to allow for a more accurate personalization of adjuvant treatments.

Background/aim: Inflammatory bowel diseases (IBD) are a group of conditions characterized by chronic inflammation of all or part of the digestive tract and primarily includes Ulcerative Colitis (UC) and Crohn's Disease (CD). This review has as target to summarize the complicated correlation between IBD and infections, which can affect patients' quality of life and increase substantially morbidity and mortality rates., Results: Scientific evidence in recent years shows a growing recognition of the phenomenon although the association between these two aspects is not definitively clear. Despite the fact that our understanding of this linkage is still incomplete, it is easily deducible that infections can start whether it be the onset or the relapse of IBD. In addition to this, the course of the disease predisposes the patient to numerous infections caused by the drugs used to treat IBD and this also raises the risk of infection complications., Conclusions: Clinical trials have demonstrated that the combined use of immunomodulating agents may increase the risk of new infections. The infections might be intensified by an insufficient vaccination of adults with IBD. Physicians have to be aware of these risks and try to attenuate and treat them properly., Key Words: Infections, Inflammatory bowel disease, Risk factors.

Background: A positive correlation between calcium and magnesium serum levels is well known and depends upon various factors. This study aims at verifying the existence of this association in a retrospective series of patients who underwent thyroid surgery., Methods: Two hundred and eighty-five consecutive patients (202 female, 83 male, mean age 57 years) who underwent at least total thyroidectomy (TT) and had a complete clinical and biochemical pre- and postoperative evaluation were included in the study. Patients were evaluated with regard to: sex, age, indications for surgery, operative time, number of accidentally removed parathyroids, extent and time of surgery, thyroiditis, final histology, pre- and postoperative levels of calcium, magnesium, vitamin D, and creatinine, presence of symptoms of hypocalcemia. Statistical analysis was performed using the R software., Results: In the postoperative period, biochemical hypocalcemia (<8.5 mg/dL) was observed in 126 patients (44%) and severe hypocalcemia (<7.5 mg/dL, a level indicating the need for longer hospitalization) was seen in 40 (14%). When analyzing patients with and without postoperative hypocalcemia, the factors affecting postoperative biochemical hypocalcemia were: older age (P=0.019), longer operative time (P=0.039), and a highly significant correlation between postoperative calcium and magnesium levels (r=0.432; P<0.001)., Conclusions: The only factor among the ones we analyzed in this retrospective study that would appear to be linked to the onset of clinically relevant hypocalcemia is low magnesium levels in the postoperative period. A prospective randomized study with a group of patients undergoing magnesium replacement in the postoperative period can clarify the possible role of magnesium repletion on hypocalcemia.

Background: The incidence of trocar site hernia (TSH) in single-port laparoscopic cholecystectomy (SPC) is still a debated issue. Aim of this retrospective study was to compare the incidence of postoperative hernia and cosmetic results among patients undergoing SPC and multiport laparoscopic cholecystectomy (MPC) performed at a single institution. Methods: A series of 60 SPC and 60 MPC patients operated on between July 2016 and May 2018 were compared. Primary endpoint was to assess the incidence of TSH at long term. All the patients were admitted as outpatients for physical examination and scar measurement. Secondary endpoints were the cosmetic results assessed by a cosmesis score (CS) and the body image questionnaire (BIQ). Results: After a median 18-month follow-up (range: 6-29 months), a hernia in umbilical trocar site was detected in 4 (7.1%) SPC patients and 1 (2%) MPC patient, the difference not being statistically significant ( P  = .216). BIQ was almost equivalent in SPC and MPC groups (5.15 versus 5.27; P  = .518), respectively. Statistically significant differences in favor of SPC were found in CS (22.3 versus 19.72; P  = .001) and in total length of scars (1.2 cm versus 4 cm; P  < .001). Conclusions: SPC technique has proved to be safe and effective in experienced hands. Superior cosmesis of SPC over MPC is confirmed, but close attention to fascial closure is a vital component of SPC, and surgeons performing single-site surgery need to be aware of this increased potential for hernia formation.

Background: The treatment of acute diverticulitis is a matter of debate and has undergone significant changes. Currently the main focus of surgical treatment is a more conservative and less invasive management., Aims and Methods: To focus the role of surgery in the treatment of acute diverticulitis, the Authors have conducted a review of the literature of the last two decades and have revised critically their own experience., Results: The indications for elective surgery based on the number of episodes, the young age at diagnosis and the presence of risk factors such as immunosuppression, have to be overcome in favour of a more individual approach based on the severity of the disease. Similarly the presence of pneumoperitoneum is no longer a compelling indication for urgent surgery just as it was in the past. In the treatment of complicated diverticulitis with abscess (Hinchey I-II) is used more and more conservative treatments consisting of guided percutaneous drainage combined with antibiotics. Resection with primary anastomosis with or without diverting ileostomy is preferable to Hartmann's procedure in case of perforated diverticulitis with peritonitis (Hinchey III-IV), using the latter only in the case of comorbidities, severe sepsis, hemodynamic instability or longtime feculent peritonitis (Hinchey IV). Recently, laparoscopic peritoneal lavage was introduced in the treatment of diverticulitis., Conclusions: Thanks to the progress made in conservative and interventional treatment and laparoscopic surgery, an increasingly less invasive treatment is proposed in the management of acute diverticulitis., Key Words: Acute diverticulitis, Laparoscopic surgery, Surgical treatment.

THE CERVICAL BRANCHES OF THE VAGUS NERVE THAT ARE PERTINENT TO ENDOCRINE SURGERY ARE THE SUPERIOR AND THE INFERIOR LARYNGEAL NERVES: their anatomical course in the neck places them at risk during thyroid surgery. The external branch of the superior laryngeal nerve (EB) is at risk during thyroid surgery because of its close anatomical relationship with the superior thyroid vessels and the superior thyroid pole region. The rate of EB injury (which leads to the paralysis of the cricothyroid muscle) varies from 0 to 58%. The identification of the EB during surgery helps avoiding both an accidental transection and an excessive stretching. When the nerve is not identified, the ligation of superior thyroid artery branches close to the thyroid gland is suggested, as well as the abstention from an indiscriminate use of energy-based devices that might damage it. The inferior laryngeal nerve (RLN) runs in the tracheoesophageal groove toward the larynx, close to the posterior aspect of the thyroid. It is the main motor nerve of the intrinsic laryngeal muscles, and also provides sensory innervation to the larynx. Its injury finally causes the paralysis of the omolateral vocal cord and various sensory alterations: the symptoms range from mild to severe hoarseness, to acute airway obstruction, and swallowing impairment. Permanent lesions of the RNL occur from 0.3 to 7% of cases, according to different factors. The surgeon must be aware of the possible anatomical variations of the nerve, which should be actively searched for and identified. Visual control and gentle dissection of RLN are imperative. The use of intraoperative nerve monitoring has been safely applied but, at the moment, its impact in the incidence of RLN injuries has not been clarified. In conclusion, despite a thorough surgical technique and the use of intraoperative neuromonitoring, the incidence of neurological complications after thyroid surgery cannot be suppressed, but should be maintained in a low range.

In cystic fibrosis (CF) patients early antibiotic treatment of lung infection has been shown to lead to Pseudomonas aeruginosa eradication. The present study determined: 1) the time period from eradication to new P. aeruginosa acquisition; 2) P. aeruginosa re-growth and new acquisition; and 3) the impact of eradication therapy on lung function, antimicrobial resistance, emergence of other pathogens and treatment costs. Ciprofloxacin and colistin were used to eradicate P. aeruginosa in 47 CF patients. Bacterial pathogens, lung function decline, P. aeruginosa antimicrobial resistance and anti-pseudomonal serum antibodies were assessed quarterly and compared with an age-matched CF control group. Additionally, costs of antibiotic therapy in both groups were assessed. Early antibiotic therapy leads to a P. aeruginosa free-period of a median (range) of 18 (4-80) months. New acquisition with different P. aeruginosa genotypes occurs in 73% of episodes. It also delays the decline of lung function compared with chronically infected patients, prevents the occurrence of antibiotic resistant P. aeruginosa strains, does not lead to emergence of other pathogens, and significantly reduces treatment costs. The treatment substantially lowers P. aeruginosa prevalence in CF. In conclusion, early antibiotic therapy exerts beneficial effects on the patient's clinical status and is cost-effective compared with conventional antibiotic therapy for chronically infected cystic fibrosis patients.