Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Emerging and re-emerging infectious disease in otorhinolaryngology.

SUMMARY: Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.

Papillary squamous cell carcinoma of the palatine tonsil: a rare cancer of the head and neck.

Papillary squamous neoplasms of the upper respiratory tract are rare variants of squamous cell carcinomas. They are characterised by an exophytic, papillary growth and generally have favourable prognosis. The tumour has been described in the upper aerodigestive tract. In this context, most common sites of involvement are the larynx and hypopharynx, and rarely the oral cavity and oropharynx. The limited studies and small number of published cases of papillary squamous cell carcinoma of the palatine tonsil led us to make a complete analysis of this tumour by analysing the clinical, histological, radiological, virological and therapeutic aspects that are not always present in the literature. A case of papillary squamous cell carcinoma of the palatine tonsil is reported. The lesion (T2N0M0) was located into the left palatine tonsil that hung towards the oral cavity. Both HPV 16 DNA and E6/E7 mRNA were detected in the lesion. The clinicopathological profile of the neoplasm is presented and a comprehensive review of recent literature was made by analysing all aspects of interest of this neoplasm.

Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies.

Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement.

Audiological findings in a case of cerebellar angioreticuloma.

The aetiology of neurosensorial damage with unilateral hearing loss and/or tinnitus and dizziness can often be difficult to determine because they may be caused wide variety of pathologic processes and a variety of diagnostic tests are needed in initial evaluation. In this paper, the authors describe, the techniques and indications of neuroimaging for evaluation of auditory symptoms. Auditory brainstem response (ABR) testing is still the choice when condition is suspected. We present a study of one patient with unilateral tinnitus, with no significant hearing loss and normal ABR: the patient underwent MRI of the district brain and the internal auditory channel (AIC) that showed the presence of a rare intracranial neoplasm, namely cerebellar angioreticuloma.

Post-laryngectomy voice rehabilitation with voice prosthesis: 15 years experience of the ENT Clinic of University of Catania. Retrospective data analysis and literature review.

This study reports our 15-year experience, in Sicily, with the use of voice prostheses, analysing the different variables that have influenced the success or failure of speech rehabilitation. The retrospective clinical analysis was carried out by reviewing the clinical histories of 95 patients with laryngeal cancer, in whom a voice prosthesis had been placed by trachea-oesophageal puncture between 1998 and 2013. Age, type of tumour, type of surgery, use of prior radiation therapy, type of puncture, prosthesis used and its duration, number of replacements, complications and causes for prosthetic success or failure were analysed. The results showed a mean of Harrison-Robillard-Schultz (HRS) TEP rating scale of 11.8 in primary TEP and 12.6 in secondary TEP (P =0.613). PORT did not affect overall rehabilitation success. In these patients, the mean HRS rating scale was 11.2, with long-term success of 85% (P =0.582). In patients over 70 years old, long-term success was 82.5%, with 78% in primary and 86% in secondary TEP, the mean HRS was 11.2 in primary and 12 in secondary TEP (P =0.648). In total, long-term success was 87.5%, with 84% in primary and 91% in secondary TEP. The results obtained by retrospective analysis of 15 years of prosthetic rehabilitation in the Sicilian territory highlighted standard rehabilitation, in terms of intra and postoperative complications, fistula related pathology and overall success.

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.

Use of sedative and analgesic drugs in the first week of ICU stay in high-level-of-care.

AIM: The aim of this study was to update the current practice of pharmacological sedation and analgesia in Italian intensive care units. DESIGN: observational, prospective, cohort study involving consecutive patients admitted during 5 months in 1999. PATIENTS were evaluated for the first 7 days of high-level-of care. SETTING: 45 adult general intensive care units. PATIENTS: 388 fulfilling enrollment criteria: admission diagnosis out of non-traumatic cerebral hemorrage, stroke, respiratory failure in chronic obstructive pulmonary disease (COPD), acute lung injury/distress syndrome (ALI/ARDS), polytrauma, head trauma, cardiac failure and major abdominal surgery; unit stay longer than 47 hours and high-level-of care treatment. RESULTS: Sedation pattern was different among diagnosis-groups. No therapy was registered in 18.8% of overall days in polytrauma vs 67.6% of cardiac patients. Opioids supply ranged from 10.1% of overall days of acute on COPD patients vs 51.4% of polytrauma patients. Propofol was the more prescribed drug, followed by opioids and benzodiazepines. Propofol was at the top in cerebrovascular disease, ALI/ARDS and COPD; opioids in abdominal surgery and trauma, benzodiazepines in cardiac failure. The average number of prescribed drugs per day was 1.5 ranging from 1.2 on COPD to 1.7 in head trauma. CONCLUSION: Diagnosis influences the pattern of sedation-analgesia during high-level-of-care period. Sedation prevalence is reasonably prescribed in trauma groups while it remains low in ALI/ARDS, post-operative, cerebrovascular, COPD and hearth failure. Particularly opioid use remains limited in post-operative patients. This surveys shows a poorly standardised sedation approach to the different phases of the therapy: induction, short and long-term sedation phase.

Endovascular treatment of iliocaval occlusion caused by retroperitoneal fibrosis: late results in two cases.

We report two cases of iliocaval occlusion caused by retroperitoneal fibrosis; one presented acute symptoms and one chronic. Both were treated by use of transluminal angioplasty and stenting with excellent clinical, hemodynamic, and imaging results at 36 and 51 months. These cases confirm the benefit of endovascular techniques in the treatment of nonmalignant obstructive disease of large veins, and specifically in the case of retroperitoneal fibrosis.

Day surgery for mucosal-hemorrhoidal prolapse using a circular stapler and modified regional anesthesia.

PURPOSE: In 1993, prolapse reduction using the circular stapler for the treatment of hemorrhoidal disease was proposed. The procedure is characterized by minimal postoperative pain. In this study we evaluated the above technique using regional anesthesia to identify the advantages and feasibility of stapled hemorrhoidectomy, with special focus on the efficacy of same-day discharge. METHODS: From December 1997 to November 1999, we performed 70 consecutive reduction corrections of mucosal hemorrhoidal prolapse using the circular stapler with regional anesthesia (a technical modification of Marti's posterior perineal block). Our series included 41 males and 29 females with a mean age of 43.4 (range, 25-74) years. Three patients were affected by second-degree hemorrhoids and 67 by third-degree hemorrhoids. RESULTS: Sixty-two patients were discharged three hours after the operation in good general condition and without pain, whereas eight patients were discharged the day after for early complications, consisting of two cases of early bleeding, three cases of urinary retention, and three cases of persistent severe pain requiring prolonged medical treatment. CONCLUSION: Our study shows that, in selected cases, it is possible to perform day surgery for patients with hemorrhoidal disease using a circular stapler device when combined with regional anesthesia.

Surgical venous thrombectomy.

Rehabilitation of the technique of venous thrombectomy is justified, but, in order for this technique to be effective, it must only be performed in selected cases. In the authors' view it is of the utmost value in young patients when the venous thrombosis occurs accidentally, after traumatism or surgery and when a diagnostic is made without delay.

Bilateral dissection of the internal carotid artery at the base of the skull due to blunt trauma: incidence and severity.

Between January 1, 1992 and December 31, 1996, a total of 1095 head trauma vicims were admitted in our intensive care unit. If CT scans demonstrated ischemic brain lesions, arteriography to visualize supraaortic vessels was performed. Carotid artery dissection was observed in ten patients (0.91%) and was bilateral in eight patients (0.73%). In the bilateral carotid artery dissection (BCAD) group, there were five women and three men, with a mean age of 35.2 years (range: 17 to 54 years). Injuries resulted from traffic accidents in seven patients and a fall in one patient. Upon admission, six patients presented with alteration of consciousness and three with hemiplegia or hemiparesia, associated with aphasia in two cases. In two other cases, hemiplegia occurred 24 hr and 13 days after the accident. All patients had brain infarction, which was unilateral in five cases and bilateral in three cases. The severity of lesions was graded on the basis of arteriographic findings as follows: Type I, wall involvement without significant stenosis or dilation; Type II, arterial dissection with stenosis >70% (Type IIA) or dilatation >50% (Type IIB) and the normal diameter of the proximal or distal internal carotid artery; and Type III, thrombosis of the internal carotid artery. Lesions were asymmetrical in six patients, including two with Type II and III lesions and four with Type I and II lesions, and symmetrical in two patients, including one with bilateral Type III lesions and one with bilateral Type II lesions. Surgery was performed in two patients with Type II lesions, including one case associated with contralateral carotid thrombosis. The intrapetrous carotid artery was exposed by an ear-nose-throat (ENT) surgeon and repaired by interposition grafting. Follow-up in these two surgical cases was 28 and 31 months. In the remaining six cases, medical treatment was performed. Outcome in nonsurgical cases was variable: death in two cases at 31 and 43 days after the accident, severe permanent hemiplegia in two cases, and minimal or no sequels in two cases. Following blunt trauma, arteriography of supraaortic vessels should be performed to detect BCAD in any patient with immediate or delayed neurologic symptoms that cannot be explained by CT-scan findings. To better understand the natural course of these lesions and define the indications for surgery, we propose a three-grade classification according to arteriographic findings. If surgery is undertaken, vein grafting should be performed following resection of the carotid artery lesions.

Pregnancy and delivery in Ehlers-Danlos syndrome type V.

Ehlers-Danlos syndrome (EDS) is a hereditary dysplasia of connective tissue with an abnormal collagen synthesis. It is characterized by hyperelasticity and fragility of the skin, joint hyperlaxity and fragility of the blood vessels. We describe the problems reported during pregnancy and delivery in women with EDS. Our patient had a type V syndrome. Accurate monitoring during the course of pregnancy is necessary. We believe cesarean section more appropriate than vaginal delivery in order to avoid the risks related to the rupture of the pelvic and perineal vessels which may be difficult to suture.

[Recurrence following surgery of the gastrocnemius veins]. / Récidives après chirurgie des veines jumelles.

Routine preoperative investigation of chronic venous insufficiency of the lower limbs with echo-Doppler has brought to light the presence of reflux into the gastrocnemius veins in almost 30% of the patients. Surgical treatment to stop this reflux consists in dividing the gastrocnemius vein flush to the popliteal vein. Early postoperative investigation of patients operated on in this way, who are symptomless and with no residual varices, has revealed the presence of persistent, symptomless, postoperative reflux into the gastrocnemius veins. One hundred and six patients were checked six months postoperatively by Duplex Doppler scanning. On the basis of the anatomical and functional findings, postoperative incompetence of the gastrocnemius veins could be classified into several types according to the cause: 1. Persistence of a complete and incompetent gastrocnemius vein, probably missed at operation: 16 patients (15%). 2. Neoangiogenesis: 11 patients (10%). 3. Persistence of an incompetent lower gastrocnemius perforating vein: 17 patients (16%). Thus, echography has revealed that in 44 lower limbs out of 106 (42%) in which the gastrocnemius veins were operated on, six months postoperatively evidence of reflux into the gastrocnemius venous network was present. All these patients were asymptomatic. In a sub-group of 48 lower limbs which had an interval Doppler check at 2 months: 6 already showed a reflux (12.5%), in 11 the gastrocnemius reflux appeared between the second and the sixth months (23%), 31 showed no reflux at 6 months (64.5%). From these findings, certain rules on the surgery of the gastrocnemius veins have been drawn up.

[Surgery of the perforating veins of the leg: open and endoscopic techniques]. / Chirurgie des veines perforantes jambières: les techniques à ciel ouvert et endoscopiques.

Surgical treatment of incompetent perforating veins of the leg is best carried out through a sub-aponeurotic approach after localisation by coloured Duplex-Scanning. Open techniques are long established. When there is only one perforator, a short 5 cm approach is centred over the previously localised perforator. In the presence of multiple perforators, an extensive approach is necessary. This usually means a single long incision, situated para-tibially in the Linton approach, postero-medially in the Dodd approach or posteriorly in the Felder approach. The advantage of the last two approaches is that they are situated at a distance from any eventual cutaneous lesion. The approach can also be through several separate oblique incisions (De Palma). More recently introduced, endoscopic techniques have the advantage of reducing the incidence of cutaneous complications such as necrosis or infections and of shortening the duration of hospitalisation. Some authors work with re-usable instruments. The perforators are divided after coagulation (Hauer, Sattler). Others use disposable instruments, insufflate the sub-aponeurotic space and clip the perforators to prevent bleeding (Gloviczki). These techniques are currently undergoing evaluation.

Blunt injury to the internal carotid artery at the base of the skull: six cases of venous graft restoration.

PURPOSE: Blunt injuries to the internal carotid artery (ICA) at the base of the skull are uncommon but potentially dangerous lesions whose management remains unclear. We report a new surgical approach of the intrapetrosal portion of the ICA that was used in six patients with the help of an ear, nose, and throat surgeon. METHODS: During a 70-month period, seven consecutive patients (four women, three men; mean age, 35.7 years; range, 21 to 59 years) were admitted, six after a motor vehicle accident and one after a cervical manipulation. All patients had a neurologic deficit. An arteriographic scan revealed four unilateral ICA lesions: two false aneurysms, one tight stenosis, and one dissection; two cases of bilateral ICA dissection were mentioned, and one case of ICA dissection was associated with a contralateral ICA thrombosis. RESULTS: One patient died before surgery, and six patients underwent a unilateral venous graft restoration, reaching the vertical portion of the intrapetrosal ICA in two patients and the horizontal portion in four. A shunt was used in one patient. Failure to recognize the end of the ICA lesion was responsible for one postoperative asymptomatic graft thrombosis (17%), but this difficulty was overcome by using intraoperative angioscopy in the other patients. No deaths and no new strokes were noted during postoperative and midterm follow-up (mean follow-up, 34 months). Five postoperative facial pareses occurred and were totally regressive within 3 to 6 months in four patients; one total deafness was recorded. CONCLUSION: Venous graft restoration of traumatic ICA lesions at the base of the skull can safely be performed with such an approach, thus producing highly satisfactory results. Before undergoing surgery, the patient must be aware of the risk of facial and auditive disorders, which are generally temporary.

Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone.

Seventy-eight premenopausal women affected by benign endometrial hyperplasia (60 simple and 18 complex) were treated from the 10th to the 25th day of the menstrual cycle with a vaginal cream containing 100 mg of natural micronized progesterone in polyethylene glycol base. The treatment lasted 3 months in 58 patients and 6 in the other 16 patients. Four patients were lost from the study. We observed a total of 67 complete regressions (90.5%) of which 58 (78.3%) occurred in the first 3 months and 9 (11.5%) after 6 months of treatment. Simple hyperplasia showed a significantly higher response to treatment in comparison with the complex type (P < 0.001). The most frequent endometrial pattern detected in the patients in whom hyperplasia regressed was of a secretive type. Recurrence of hyperplasia occurred in 1 out of 58 (1.72%) patients at the 3rd month and in 3 out of 49 (6.1%) patients at the 6th month after treatment. There were no significant differences between the two hystological groups in the percentage of recurrence. During treatment we observed a significant reduction of the amount, duration and frequency of the menstrual bleeding. Minimal side-effects were observed. In conclusion, for its effectiveness and safety, vaginal administration of natural micronized progesterone seems to be an interesting approach to benign endometrial hyperplasia, particularly indicated in women also affected by metabolic disorders.

[Continuous postmenopausal estrogen-progesterone therapy]. / EPRT continua in postmenopausa.

In this study menopausal symptoms, endometrial histology, uterine bleeding pattern, plasma lipid concentrations, bone mineral loss, body weight and blood pressure have been evaluated in postmenopausal women who received continuous conjugated equine estrogens and medrogestone over a 1 year treatment period. By the third month of therapy we detected a significant (p < 0.01) improvement in postmenopausal symptomatology. At the 6th and 12th month, endometrial biopsy specimens revealed atrophic endometrium in all women. Uterine bleeding episodes were observed especially during the first months of treatment. Amenorrhoea was found in all patients only after 8 months of therapy. By the 6th month of therapy, we observed a significant (p < 0.01) decrease of plasma cholesterol and low-density lipoprotein cholesterol levels. Instead, plasma high-density lipoprotein and triglycerides concentrations didn't show significant variation from baseline values. No significant changes in bone mineral density could be detected after 12 months of treatment. Body weight and blood pressure were not significantly altered from baseline. This study suggests that continuous conjugated equine estrogens plus medrogestone treatment appears to be an interesting and safe manner to administer postmenopausal hormone replacement therapy. This regimen could represent a good alternative to sequential estroprogestin therapy in women who do not tolerate withdrawal bleeding.