Electrochemotherapy as palliative treatment in patients with recurrent and/or metastatic head and neck tumours: features analysis for an early determination of the partial responsive patients.

OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies. PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR. RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%. CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study.

BACKGROUND: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions. METHODS: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed. RESULTS: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047). CONCLUSION: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.

Assessment of the Clinical Impact of a Liver-Specific, BCAA-Enriched Diet in Major Liver Surgery.

BACKGROUND: The relationship between nutrition and liver disease is relevant for the outcome after surgery. Patients with liver cirrhosis characteristically show protein-energy malnutrition with decreased levels of branched-chain amino acids (BCAA) and increased levels of aromatic amino acids. MATERIALS AND METHODS: We conducted a prospective controlled clinical trial including 57 patients after liver transplantation or major liver resection surgery in order to test the effect of early postoperative nutrition on the outcome and nutrition profile of these patients. The test group received a dietetic program composed of ingredients naturally rich in BCAA (BCAA group), and the control group received standard hospital meals. Patient survival, liver function tests, subjective well-being, and a nutritional status including amino acid profiles were analyzed immediately and 14 days after major liver surgery (secondary end points). General health and well-being were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (primary end point). RESULTS: In-depth analysis of amino acid profiles was performed for patients undergoing liver resection (n = 21) and liver transplantation (n = 36). Interestingly, amino acid profiles did not correlate with body mass index or the Model for End-Stage Liver Disease score. Patients scheduled for liver transplantation showed significantly lower levels of BCAA pretransplant compared to patients undergoing liver resection. Patients in the liver resection subgroup were more likely to benefit from the BCAA cuisine in terms of significantly higher food intake and subjective rating. The clinical liver function tests, however, did not show statistical difference between the BCAA group and the control group in the examination period of 14 days. CONCLUSION: Our specifically designed BCAA-enriched diet resulted in greater patient satisfaction and compliance with nutrition. A larger trial or longer-term follow-up may be required to identify an effect on survival, recovery, surgical complications, protein profiles, and amino acid profiles.

Early Post-Operative Pancreatitis and Systemic Inflammatory Response Assessed by Serum Lipase and IL-6 Predict Pancreatic Fistula.

BACKGROUND: Post-operative pancreatic fistula (POPF) remains a critical complication after pancreatic resection. This prospective pilot study evaluates perioperative markers of pancreatitis and systemic inflammation to predict clinically relevant grade B/C-POPF (CR-POPF). METHODS: All patients undergoing pancreatic resection from December 2017 to April 2019 were prospectively enrolled. Surgical procedures and outcomes were correlated with perioperative blood markers. ROC analysis was performed to assess their predictive value for CR-POPF. Cut-offs were calculated with the Youden index. RESULTS: In total, 70 patients were analysed (43 pancreatoduodenectomies and 27 distal pancreatectomies). In-hospital/90-d mortality and morbidity were 5.7/7.1% (n = 4/n = 5) and 75.7% (n = 53). Major complications (Clavien-Dindo ≥ 3a) occurred in 28 (40.0%) patients, CR-POPF in 20 (28.6%) patients. Serum lipase (cut-off > 51U/L) and IL-6 (> 56.5 ng/l) on POD3 were significant predictors for CR-POPF (AUC = 0.799, 95%-CI 0.686-0.912 and AUC = 0.784, 95%-CI 0.668-0.900; combined AUC = 0.858, 95%-CI 0.758-0.958; all p < 0.001). Patients with both or one factor(s) above cut-off more frequently developed CR-POPF than cases without (100 vs. 50% vs. 7.5%, p < 0.001). This also applied for overall and severe complications (p = 0.013 and p = 0.009). CONCLUSIONS: Post-operative pancreatitis and inflammatory response are major determinants for development of POPF. A combination of serum lipase and IL-6 on POD3 is a highly significant early predictor of CR-POPF and overall complications, potentially guiding patient management. CLINICAL TRIAL REGISTRATION: The study protocol was registered at clinicaltrials.gov (NCT04294797).

Magnesium alginate in children with uncontrolled asthma.

Gastroesophageal reflux disease (GERD) may be frequently associated with asthma in children and may affect asthma control. Proton pump inhibitors (PPI) are commonly prescribed in asthmatic children, despite uncertain efficacy on respiratory symptoms and risk of relevant adverse effects.

Outcomes of pancreas retransplantation in patients with pancreas graft failure.

BACKGROUND: Pancreas retransplantation is still a controversial option after loss of a pancreatic graft. This article describes the experience of pancreas retransplantation at a high-volume centre. METHODS: This was a retrospective observational study of all pancreas retransplantations performed in a single centre between 1997 and 2013. Pancreatic graft loss was defined by the return to insulin dependence. Risk factors for graft loss as well as patient and graft survival were analysed using logistic and time-to-event regression models. RESULTS: Of 409 pancreas transplantations undertaken, 52 (12·7 per cent) were identified as pancreas retransplantations. After a median follow-up of 65·0 (range 0·8-174·3) months, 1- and 5-year graft survival rates were 79 and 69 per cent respectively, and 1- and 5-year patient survival rates were 96 and 89 per cent. During the entire follow-up, 22 grafts (42 per cent) were lost. Patient survival was not associated with any of the donor- or recipient-related factors investigated. Five-year graft survival was better after simultaneous kidney-pancreas retransplantation than pancreas retransplantation alone: 80 per cent (16 of 20) versus 63 per cent (20 of 32) (P = 0·226). Acute rejection (odds ratio 4·49, 95 per cent c.i. 1·59 to 12·68; P = 0·005) and early surgical complications (OR 3·29, 1·09 to 9·99, P = 0·035) were identified as factors with an independent negative effect on graft survival. CONCLUSION: Pancreas retransplantation may be considered for patients whose previous graft has failed.

Integrating interventional oncology in the treatment of liver tumors.

BACKGROUND: Percutaneous ablation techniques offer a vast armamentarium for local, minimally invasive treatment of liver tumors, nowadays representing an established therapeutic option, which is integrated in treatment algorithms, especially for non-resectable liver tumors. The results of ablative treatment compare very well to surgical treatment in liver lesions, and confirm that these techniques are a valuable option for bridging for transplantation. Different techniques have been established to perform tumor ablation, and the feasibility varies according to the procedure and technical skills of the operator, depending on the size and location of the liver lesion. In recent years, stereotactic multi-needle techniques using 3D trajectory planning, general anesthesia, and tube disconnection during needle placement have had a strong impact on the application range of ablation for liver tumors. CONCLUSION: It is well known that creating a sufficient ablation margin and overlapping ablation zones is one key issue to enable ablation of large liver lesions with tumor-free margins (A0 ablation in analogy to R0 resection). Image fusion during treatment and follow-up assure highly accurate staging procedures and interventional planning. NOVEL ASPECTS: Review on the standards in ablation techniques for the treatment of liver tumors. Update on different ablation techniques, indications, and contraindications for percutaneous liver tumor treatment. Summary of recently published reports on liver tumor ablation.

Transoral robotic surgery of parapharyngeal space tumours: a series of four cases.

Tumours arising from the parapharyngeal space (PPS) represent less than 1% of all head and neck tumours. Salivary gland tumours account for 40-50% of PPS lesions and are located in the pre-styloid parapharyngeal space. Pleomorphic adenomas represent 80-90% of salivary tumours in the PPS. Recently, transoral robotic surgery (TORS) has become common in head and neck surgery as a minimally invasive procedure. Four cases of benign PPS tumour treated with TORS are presented here. Preoperative diagnosis was conducted by fine needle aspiration biopsy and magnetic resonance imaging, and the results were used to plan the correct surgical approach. One case required a change of approach to conventional transoral blunt dissection. Patients required pain control and reported dysphagia symptoms for a period of weeks, but no nasogastric tube was needed at any time. This case series indicates that TORS is a safe surgical procedure for the excision of benign tumours of the PPS in selected cases.

Local vs general anaesthesia in the development of neurosensory disturbances after mandibular third molars extraction: A retrospective study of 534 cases.

BACKGROUND: The choice of the anaesthetic modality is one of the primary steps during planning of third molar surgery. The aim of the present study was to compare the risk of developing neurological injures of the inferior alveolar nerve (IAN) and lingual nerve (LN) in patients treated for wisdom teeth removal under general anaesthesia (GA) with a group treated under local anaesthesia (LA). MATERIAL AND METHODS: This is an observational retrospective, unicentric study; between September 2013 and September 2014, 534 patients underwent third molar surgery, 194 (36,3%) under GA and 340 (63,7%) under LA by the same oral surgeon. Difference in the incidence of IAN and LN injures between groups have been statistically analyzed with Fisher exact test and estimated odd ratio for development of such complications has been calculated. RESULTS: In GA patients the incidence of IAN and LN injures was 4.6% and 2.1%, respectively while in the LA group it was and 0.3% and 0%, respectively. A significant difference in IAN and LN involvement between groups was observed (IAN lesion: Fisher exact test, p<0.001; LN lesions: Fisher exact test, p<0.05). The estimated odd ratio for development of IAN injures after GA was 16.49 (95% CI: 2.07-131.19) and was not calculable for LN injures because no cases were observed in the LA group. CONCLUSIONS: Since GA is a perioperative variable that seems to significantly increase the risk of developing IAN and LN lesions, when treating patients that request GA, they must be adequately informed that an higher incidence of post-surgical sensory disturbances is expected.

Sodium hyaluronate improves quality of life and nasal endoscopy features in preschool children with upper respiratory tract infections.

The aim of this prospective, randomised study was to evaluate the effects of nasal douches with sodium hyaluronate on clinical and endoscopic variables, on parental perception of their child’s health-related quality of life (HR-QoL), and on parental workdays lost in preschool recurrent upper respiratory tract infections (URTIs). Children aged 2-6 years with recurrent or persistent URTIs underwent at baseline the evaluation of upper respiratory tract symptoms in the previous two weeks, and nasal endoscopy. Parents of enrolled children were assessed for self-perception of their children’s HR-QoL using a standardised questionnaire. The same variables were reassessed after a 2-week treatment with either 9 mg sodium hyaluronate plus saline solution or saline alone by nasal douches. Forty of the 48 children enrolled completed the study (22 assigned to the combined treatment). Compared to baseline, the combined treatment resulted in a significant reduction of the prevalence of children with missed daycare days (45% vs 14%, p=0.04) and of parents with workdays lost (36% vs 5%, p=0.02), and in a significant improvement of HR-QoL score (3.7 vs 2.8, p=0.004). At endoscopy, the secretion and mucosal oedema score significantly improved after the combined treatment (6 vs 2, p < 0.001), and there was a trend towards a reduction of the adenoid hypertrophy score (p=0.06). No clinical, HR-QOL or endoscopy changes were found in the saline group. In preschool children with recurrent or persistent URTIs, sodium hyaluronate by nasal douche significantly improves endoscopic features. Additional benefits include the children’s HR-QoL and daycare attendance, and parental work.

Prevalence, diagnosis and management of ectopic thyroid glands.

Ectopic thyroid tissue (ETT) is an uncommon entity that may be found anywhere along the line of the obliterated thyroglossal duct, usually from the tongue to the diaphragm. We performed a retrospective analysis of patients undergoing surgical treatment for thyroid disease between January 2000 and December 2013, seeking for ETT All patients with prior neck surgery or trauma were excluded. The clinic-pathologic features, prevalence and diagnosis of the lesions were collected and analyzed. Out of 3092 included patients, 28 ETT were identified (0.9%). The anatomical site of ETT was as follows: lateral cervical in 6 (21.4%), along the thyroglossal duct in 6 (21.4%), mediastinal in 5 (17.9%), lingual in 5 (17.9%), sublingual in 3 (10.7%), and submandibular in 3 (10.7%). Histopathology revealed 27 benign lesions and 1 (3.6%) papillary carcinoma. ETT is found in less than 1% of patients receiving thyroid surgery. Diagnosis of ETT requires clinical imaging. Surgery is a prudent choice due to the potential of malignant evolution of ETT.

Calibre Persistent Labial Artery: Clinical Features and Immunohistochemistry Diagnosis.

Calibre persistent labial artery (CPLA) usually presents as an asymptomatic papule on the lower lip and can be easily misdiagnosed as a mucocele, haemangioma, venous lake, varix or fibroma. When it is ulcerated, squamous cell carcinoma is the most usual differential diagnosis. Here, we report a case of a 25-year-old woman with no previous relevant medical history who presented with a complaint of an asymptomatic, non-ulcerated, progressively growing nodule (over the last 5 months) on the upper lip. In this case, the diagnosis was made clinically and confirmed by immunohistochemical analysis. We conclude that clinicians should be aware of CPLA and it should be included in the differential diagnosis of labial mucosal papules. Sometimes, the immunohistochemical analysis is necessary to make a correct diagnosis.

Treatment with tetrahydrobiopterin overcomes brain death-associated injury in a murine model of pancreas transplantation.

Brain death (BD) has been associated with an immunological priming of donor organs and is thought to exacerbate ischemia reperfusion injury (IRI). Recently, we showed that the essential nitric oxide synthase co-factor tetrahydrobiopterin (BH4) abrogates IRI following experimental pancreas transplantation. We therefore studied the effects of BD in a murine model of syngeneic pancreas transplantation and tested the therapeutic potential of BH4 treatment. Compared with sham-operated controls, donor BD resulted in intragraft inflammation reflected by induced IL-1ß, IL-6, VCAM-1, and P-selectin mRNA expression levels and impaired microcirculation after reperfusion (p < 0.05), whereas pretreatment of the BD donor with BH4 significantly improved microcirculation after reperfusion (p < 0.05). Moreover, BD had a devastating impact on cell viability, whereas BH4-treated grafts showed a significantly higher percentage of viable cells (p < 0.001). Early parenchymal damage in pancreatic grafts was significantly more pronounced in organs from BD donors than from sham or non-BD donors (p < 0.05), but BH4 pretreatment significantly ameliorated necrotic lesions in BD organs (p < 0.05). Pretreatment of the BD donor with BH4 resulted in significant recipient survival (p < 0.05). Our data provide novel insights into the impact of BD on pancreatic isografts, further demonstrating the potential of donor pretreatment strategies including BH4 for preventing BD-associated injury after transplantation.

Defect chemistry in ferroelectric perovskites: long standing issues and recent advances.

Accurate control of residual defect density is required for reliable investigation and use of ferroelectric materials. After reviewing the long term endeavor to decrease defect contributions in bulk materials, which reached mass production decades ago, recent challenges are underlined. These mostly result from the continuous trend towards integration which has reached the nanometre range. The contribution of solid state chemistry is of key relevance for improving the present processing routes and suggesting alternative ones, for example by controlling a large density of charged defects to reach unprecedented functionalities. Some of these breakthroughs are reviewed.

Systematic tuning of the conduction mechanisms in ferroelectric thin films.

We have investigated the macroscopic and microscopic properties of large sets of Ba0.7Sr0.3TiO3 thin films including several substitution rates of manganese. Thanks to a high degree of control of the processing parameters at each stage we have been able to find a link between the dc leakage current and the low and high frequency dielectric permittivity and losses. We supplemented these macroscopic observations with in depth investigations of the defect states through x-ray photoelectron spectroscopy. We found that both the leakage current and the extrinsic dielectric parameters arise from a large density of charged point defects related to oxygen vacancies. At the outer surfaces of the films, the density of such charged defects is so high that it can raise the Fermi level to close to the conduction band. Such degradation of the films' performance can be relieved by appropriate manganese substitution for the titanium host ions. Such doping is able to move back the Fermi level to close to the center of the bandgap thus changing the conduction process from interfacial Schottky to bulk Poole Frenkel and decreasing the extrinsic losses. This beneficial effect was already inferred in ceramics and thin films but we have established a clear link between the macroscopic parameters and the microscopic defect state. This model can be transferred to many high permittivity oxides.

Donor pretreatment with tetrahydrobiopterin saves pancreatic isografts from ischemia reperfusion injury in a mouse model.

Depletion of the nitric oxide synthase cofactor tetrahydrobiopterin (H4B) during ischemia and reperfusion is associated with severe graft pancreatitis. Since clinically feasible approaches to prevent ischemia reperfusion injury (IRI) by H4B-substitution are missing we investigated its therapeutic potential in a murine pancreas transplantation model using different treatment regimens. Grafts were subjected to 16 h cold ischemia time (CIT) and different treatment regimens: no treatment, 160 µM H4B to perfusion solution, H4B 50 mg/kg prior to reperfusion and H4B 50 mg/kg before recovery of organs. Nontransplanted animals served as controls. Recipient survival and endocrine graft function were assessed. Graft microcirculation was analyzed 2 h after reperfusion by intravital fluorescence microscopy. Parenchymal damage was assessed by histology and nitrotyrosine immunohistochemistry, H4B tissue levels by high pressure liquid chromatography (HPLC). Compared to nontransplanted controls prolonged CIT resulted in significant microcirculatory deterioration. Different efficacy according to route and timing of administration could be observed. Only donor pretreatment with H4B resulted in almost completely abrogated IRI-related damage showing graft microcirculation comparable to nontransplanted controls and restored intragraft H4B levels, resulting in significant reduction of parenchymal damage (p < 0.002) and improved survival and endocrine function (p = 0.0002 each). H4B donor pretreatment abrogates ischemia-induced parenchymal damage and represents a promising strategy to prevent IRI following pancreas transplantation.

[Measles and its secondary pulmonary complications: prevention is better than treatment]. / Il morbillo e le sue complicanze polmonari secondarie: prevenire è meglio che curare.

Recent measles outbreaks observed in North America and in several European countries, including Italy, raised the attention about the risks linked to this infection and the need of implementing and maintaining adequate preventive strategies. Measles may cause several respiratory complications such as chronic obstructive lung disease, pneumonia, with subsequent development of chronic suppurative lung disease, giant cells pneumonia or progressive respiratory insufficiency. The current preventive strategies aim to improve vaccination coverage rates with 2 doses of measles-mumps and rubella vaccine, and to catch up individuals who have not been previously vaccinated. The present review analyses pulmonary complications of measles and measles preventive strategies. Elimination of measles is a feasible goal. Since measles complications are preventable by vaccination, improvement in vaccination coverage is highly desirable.

Peripheral neurological damage following lower third molar removal. A preliminary clinical study.

AIM: Type of impaction and site of nerve are important risk factors of neurological damage following the lower third molar removal. The purpose of this study was to evaluate the peripheral damage of lingual and lower alveolar nerves in relation to tooth angulation and radiographic proximity to the alveolar canal. METHODS: Sixty-seven consecutive patients (41 women and 26 men, mean age 29.97+/-14.35 years) underwent lower wisdom teeth extraction and were clinically evaluated over a one year period, checking any evidence of peripheral damage of the lower alveolar or lingual nerves. Tooth angulation and presence or absence of spongy bone between the mandibular canal and the root apex were considered; so, the patients were assigned twice to two groups: G1A (third molar in axis); G2A (third molar angulated); G1B (third molar apex adjacent to the mandibular canal); G2B (spongy bone between root apex and canal). The extraction was carried out according to a standardised technique without raising and retracting of a lingual flap. The follow-up checks were at one week, 1, 3, 6, 12 months and until any problem was solved. Statistical analysis was carried out using chi2 test. RESULTS: A total of two cases of temporary damage to the lingual nerve (1 case in G1A and 1 in G2A; 2 cases in G2B) and 3 cases to the lower alveolar nerve (3 cases in G2A; 1 in G1B and 2 in G2B) were discovered. No statistical differences were found. Symptoms cleared up within a maximum period of 5 months. CONCLUSION: Tooth angulation and proximity to lower alveolar canal were not related to alveolar or lingual damage; the conservative surgical technique seems to be an important factor in preventing neurological complications.