Real-world treatment in patients with HER2+ metastatic breast cancer : Treatment decisions in HER2+ mBC.

PURPOSE: The landscape of HER2+ metastatic breast cancer (mBC) treatment is changing due to the availability of new anti-HER2 drugs. The purpose of this study was to assess the current treatment patterns and sequences used in HER2+ mBC in the real-world setting. Secondary objectives were to describe the factors that influence the decision to prescribe a first and second-line antitumour treatment. METHODS: Retrospective chart review of 3068 cases in Spain, Italy, the Netherlands and the UK. RESULTS: First and second-line treatments and regimens are consistent with the clinical guidelines, especially for recently initiated treatments. Age and performance status (PS) of patients impact treatment patterns: younger patients received more innovative treatments than elderly patients. In addition, while most patients received a first antitumor treatment, the rate of patients who continue to subsequent lines of therapy is low (55% transitioning from 1st to 2nd line; 58% from 2nd to 3rd line). Age and PS are key factors in the decision to prescribe further antitumor treatment. CONCLUSION: Fewer HER2+ mBC patients than expected receive a second and third line therapy. Guidelines should make specific recommendations for older patients or those with a poor PS.

Italian version of ASES questionnaire for shoulder assessment: cross-cultural adaptation and validation.

The patient-oriented measures, represented by self-administered questionnaire, have become an important aspect of clinical outcome assessment. To be used with different language groups and in different countries, questionnaires must be translated and adapted to new cultural characteristics and then validated by a widely accepted process to evaluate reliability and validity, fundamental characteristic for each measure. The aim of the study is to perform the cross-cultural adaptation and to assess the Italian version instrument reliability and validity. The study design is a cross-cultural adaptation and cross-sectional study of a sample of patients affected by shoulder disorder with a subsample followed prospectively for retest reliability. The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form was culturally adapted for Italian-speaking people, following the simplified Guillemin criteria. Reliability and validity were assessed in a cross-sectional study of 50 consecutive patients affected by shoulder disorder. A sub-sample of 20 patients was followed prospectively for retest reliability. The results were compared with other validated patient-oriented measures. The ASES scales showed a high correlation with other patient-oriented measures, as hypothesized, and it also showed good values with regard to reproducibility, consistency and validity, to the original versions published in English. These findings suggest that the evaluation capacities of the Italian version of ASES are equivalent to those of English language version.

Treatment of acute grade III acromioclavicular dislocation: a lack of evidence.

BACKGROUND: Although nonoperative treatment is considered the standard of care for the treatment of grade I and II acromioclavicular joint injuries, the treatment of grade III injuries is controversial. There are as many methods of nonoperative treatment as there are for operative stabilization. That is why we conducted a literature research to find out the best evidence regarding the treatment of acute grade III acromioclavicular dislocation. METHOD: The research was limited to RCTs, systematic review and meta-analysis in the most representative databases. Even if research identifies more than 600 articles, only five were included in the study because there were RCTs, and systematic reviews, but no meta-analysis articles were found. Moreover, no meta-analysis was performed because of differences of data published in the three RCTs (different type of surgical treatments and different outcome measures). RESULTS: From the literature evaluation, clinical results seem to be comparable between the operative and the conservative treatments, but complications are more evident in the surgery group. Since there is not a preponderance of positive papers showing the benefits of a surgical technique over conservative therapy, the nonoperative treatment is still considered a valid procedure in the grade III acromioclavicular separation. CONCLUSION: More prospective randomized studies using validated outcome measures are needed to identify the suitable operation techniques for the acute injuries.

Range of motion correlates with patient perception of TKA outcome.

Despite the clinical success of total knee arthroplasty, little information can be found in the literature about the relationship between certain postoperative physical findings and the outcome. Specifically, is the range of motion related to patient perception of outcome? We performed a cohort prospective study on 48 patients assessed by patient-oriented evaluations (Short Form 36 Health Survey and Oxford Knee Questionnaire) and objective evaluations after total knee arthroplasty. Thirty-four patients were women and 14 were men. The mean age at followup was 71 years (range, 64-80 years) and the minimum followup was 20 months (mean, 28.5 months; range, 20-30 months). We found a positive correlation between range of motion and patient-oriented evaluations in some domains of the Short Form 36 and in the Oxford knee score.

The Italian version of the Oxford 12-item Knee Questionnaire-cross-cultural adaptation and validation.

Questionnaires must be translated and adapted to suit the cultural characteristics of different countries with different languages; they then need to be validated using a standard process. This was done for the Italian version of the Oxford Knee Questionnaire (OKQ), and its reliability and validity were assessed in a cross-sectional study of 50 consecutive patients referred for gonarthrosis and whose knees were replaced. A "subsample" of 20 patients was assessed prospectively to confirm the reliability of the Italian version, and these results were then compared with other clinical studies. The Italian OKQ scale correlated well with other clinical studies and also showed good results with regard to reproducibility, consistency, and validity when compared to the other published versions of the OKQ.

Patient-oriented assessment of back pain in pregnancy.

Back pain is a common symptom in women during the last period of pregnancy. Only a few studies using validated patient-oriented tools have been undertaken on this topic. We report on a multicenter study on back pain in women during the last period of pregnancy, which involved seven Italian institutions. Seventy-six women in their 8th and 9th months were studied using the Italian validated version of the Roland questionnaire -- a disease-specific patient-oriented tool for low back pain. Sixty-two percent of the women had gone through at least one previous pregnancy, and clinical data concerning both the period before all pregnancies and the period before the current pregnancy were acquired. The study found that 31% of the women had no back pain symptoms (Roland score 0), 40% scored from 1 to 4, 21% scored from 5 to 10, and 8% scored more than 10. With regard to the predictive factor, history of back pain and sciatica before the pregnancy were found to be associated with occurrence of back pain symptoms during pregnancy. Unexpectedly, our results showed that male sex of the fetus seems to be related to occurrence of back pain symptoms during pregnancy. However, back pain was not associated with having gone through previous pregnancies, nor was the Roland score related to the weight before pregnancy or to increment of weight during pregnancy. Evaluation of the patient's perspective made it possible to identify predictive factors for occurrence of back pain, thereby furnishing important information for the clinical approach to pregnancy.

Italian version of the Roland Disability Questionnaire, specific for low back pain: cross-cultural adaptation and validation.

Over the last 10 years, patient-oriented evaluations using questionnaires have become an important aspect of clinical spinal outcome studies. Any questionnaire must be translated and culturally adapted in order to be used with different language groups, and the translated version must then be evaluated for reliability and validity, which are fundamental attributes of any measurement tool. The Roland Disability Questionnaire, a low back pain disease-specific tool, was submitted to translation into Italian and to cross-cultural adaptation following the Guillemin criteria. It was then validated on 70 patients (37 male and 33 female; mean age 58, range: 28-67) suffering from low back pain as assessed by clinical examination, imaging and also electromyography in cases of suspected neurological impairment. The test-retest reliability, assessed with intraclass correlation, was 0.92 and the internal consistency reached a Cronbach's alpha of 0.82. The Italian version of the Roland Disability Questionnaire satisfied the validation criteria, showing characteristics of reliability and validity similar to previously published versions translated and adapted for other countries.

Extracorporeal shock wave therapy for chronic calcifying tendinitis of the shoulder.

Over the past few years, extracorporeal shock wave therapy (ESWT) has been introduced for the treatment of some orthopedic diseases. The aim of this study was to assess the efficacy of ESWT on chronic calcifying tendinitis of the shoulder through a prospective study. We studied 30 patients (mean age, 56.6 years) with chronic calcifying tendinitis of the shoulder. The patients were treated for a mean of 6 sessions, with 1400 impulses for each session. We used the new device Electro Medical Systems-Swiss Dolorclast (Electro Medical Systems, Nyon, Switzerland), which emits radial expanded shock waves, pneumatically generated. Patients were evaluated before treatment and after a mean of 10 weeks on a patient-oriented questionnaire (Dawson shoulder questionnaire, validated Italian version) and by radiological and ultrasound examinations. Radiographic disintegration and partial resorption of the calcium deposit were respectively recorded in 50% and 30% of cases, and the ultra-sound image showed modification of echogenicity in all cases. Clinically a good response to pain and to joint movement was recorded; the questionnaire also showed a statistically significant improvement. Shock wave therapy for calcifying tendinitis of the shoulder is effective from the patient's perspective and according to imaging outcomes. It could be considered an effective therapy for chronic calcifying tendinitis of the shoulder.

Cross-cultural adaptation of the lumbar North American Spine Society questionnaire for Italian-speaking patients with lumbar spinal disease.

STUDY DESIGN: A cross-cultural adaptation and cross-sectional study of a sample of lumbar spine patients, with a subsample followed prospectively for retest reliability. OBJECTIVES: To assess the Italian version instrument reliability and validity. SUMMARY OF BACKGROUND DATA: The orthopaedic outcome measurements have been usually focused on objective parameters as radiograph measures or other technical aspects. However, these parameters are weakly related with outcomes that are more relevant to patients as functional status and symptoms. In the last ten years, the patient-oriented measures have become an important aspect of spinal clinical outcome evaluation. The most common instruments to assess patient perspective are self-administered questionnaires that must be validated by a widely accepted process to evaluate reliability and validity, which are fundamental for every instrumental measure. METHODS: The North American Spine Society (NASS) questionnaire was culturally adapted for Italian-speaking people following the Guillemin criteria. The Italian version was tested on 74 consecutive patients who were referred to the authors' department and suffered from low back pain with leg irradiation. The results were compared with other validated patient-oriented measures. Forty-eight-hour retests were performed on a subsample of 45 patients. RESULTS: The questionnaire was favorably accepted by patients. The lumbar spine pain and disability and neurogenic symptoms subscales showed a high correlation with other patient-oriented measures, as hypothesized, and it also showed good values on test-retest. CONCLUSIONS: The questionnaire should be considered for patient health status monitoring and for clinical trials.

Carcinomas of sweat glands: report of 60 cases.

CONTEXT: Several aspects of sweat gland carcinomas (incidence, classification, diagnosis, and behavior) have not been definitively clarified and need to be studied further. OBJECTIVE: The clinicopathologic findings of a large series of sweat gland carcinomas, collected during a period of 15 years, are presented. METHODS: Sixty sweat gland carcinomas (41 porocarcinomas, 3 syringomatous carcinomas, 8 ductal carcinomas, 5 adenoid cystic carcinomas, and 3 mucinous carcinomas) were analyzed histologically and immunohistochemically. RESULTS: Porocarcinomas were composed of eosinophilic and clear atypical cells arranged in solid-cystic lobular masses. These tumors were divided into 2 subgroups: horizontal porocarcinomas, showing a prominent intraepidermal component, and nodular porocarcinomas, which demonstrated predominant nodular growth. Syringomatous carcinomas presented keratinizing and nonkeratinizing cysts, dilated tubules (sometimes with a "tadpole" appearance), small neoplastic ducts, solid islands, and cellular cords. Ductal carcinomas were characterized by a prominent formation of tubules, solid islands, and cellular cords. Adenoid cystic carcinomas presented a characteristic pattern, showing basaloid monomorphous cells with moderately atypical nuclei, arranged in cribriform or solid islands and in tubular structures. Mucinous carcinomas were composed of moderately atypical cells with eosinophilic vacuolated cytoplasm, forming solid and cystic islands floating in large mucin pools. Immunohistochemically, cytokeratin was found in neoplastic cells in all cases, carcinoembryonic antigen was detected in 73% of cases, and actin-positive (myoepithelial) cells were not found. CONCLUSIONS: Although numerous studies have been published in recent years, the histologic features, histogenesis, and classification of sweat gland carcinomas still remain controversial and need to be clarified by further studies.

Comparison of integrin alpha chain expression in benign and malignant salivary gland tumors.

OBJECTIVE: This study investigates the distribution of the alpha chain of the integrin family of extracellular matrix receptors in a series of adenomas and carcinomas of salivary gland origin to determine if the malignant phenotype is associated with modification of the expression of these receptors. STUDY DESIGN: Cryostat sections of 36 tumor specimens were stained by a standard streptavidin-biotin-peroxidase technique using primary monoclonal antibodies against alpha 1-6 and alpha v integrin chains. The immunohistochemical reaction was scored using a three-point scale and the results were analyzed using Fisher's exact test. RESULTS: In salivary adenomas, alpha 2, alpha 3, alpha 4, alpha 6, and alpha v chains were widely expressed in most of the cases studied. The alpha 1 subunit was prominently expressed by the epithelial cells of Warthin's tumor, whereas a minority of pleomorphic adenomas showed immunoreactivity for this antigen. We observed alpha 5 subunit expression only in the mesenchymal-like component of pleomorphic adenomas. In salivary carcinomas, integrin alpha chain expression was heterogeneous, varying greatly between different histotypes and within the same histotype. The distribution of the antigens was similar to that of adenomas, except for the alpha 6 chain, which localized not only at the interface between cell and matrix, but also at sites of cell-cell contact. When the immunohistochemical levels of integrin alpha chain expression were compared in adenomas and carcinomas, expression significantly decreased for the alpha 6 and alpha v chains (p = 0.0007; p = 0.002, respectively). CONCLUSIONS: Loss of alpha 6 and alpha v integrin subunits occurring in salivary gland carcinomas could modify the adhesive properties of malignant cells, contributing to the invasive potential of these tumors.

Mucinous carcinoma of sweat glands.

Three cases of primary cutaneous mucinous carcinoma of sweat gland origin are presented. Patients were a 47-year-old man and 2 females aged 70 and 71 years. The clinical and pathologic features of the described tumors were similar to those reported in the literature, except for 2 of the involved sites (abdominal skin and vulva), not previously described.

[Epidermal infiltration of melanoma]. / L'infiltrazione epidermica nel melanoma.

The infiltration of the epidermis by malignant melanocytes is a characteristic phenomenon of cutaneous melanoma. A series of consecutive unselected cutaneous melanomas was histologically reviewed in order to study the frequency and the characters of epidermal infiltration. Such a feature was found in 86% of tumors (93% in superficial spreading melanomas); it was extensive in 65% of cases, focal in 35%; topographically, it was central and peripheral in 67%, peripheral in 30%, central in 3%. Results show that epidermal infiltration, albeit inconstant, is a useful feature in the histological diagnosis of melanoma (especially in SSM), provided that it is distinguished from pseudoinfiltration, a histologically similar, but intrinsecally different, feature observed in some benign melanocytic lesions.

Immunolocalization of extracellular matrix components in mixed tumors of the skin.

Mixed tumors of the skin are characterized by a proliferation of epithelial cells embedded in a mesenchymal matrix with a wide spectrum of histologic appearances. The characterization of the extracellular matrix components of mixed tumors of the skin has so far received little attention. We performed an immunohistochemical study of type IV collagen, laminin, fibronectin, and tenascin distribution in a series of 10 mixed tumors of the skin. Laminin localized at the basement membrane around solid epithelial nests and tubulo-alveolar structures, whereas type IV collagen, fibronectin, and tenascin were also expressed in the myxoid stroma. Tenascin and fibronectin localized in the chondroid matrix. The extracellular matrix components were prominently expressed in mixed tumors of the skin, suggesting that they could play an important role in the formation and organization of myxoid and chondroid matrices and in the epithelial-mesenchymal interactions of these tumors.

Immunolocalization of alpha 2, alpha 5, and alpha 6 integrin subunits in salivary tissue and adenomas of the parotid gland.

The localization of the integrin subunits alpha 2, alpha 5, alpha 6 was studied immunohistochemically in samples of normal salivary gland and in a series of 8 pleomorphic adenomas, 5 Warthin's tumors, and 2 basal cell adenomas. In normal salivary tissue, acinar and ductal cells expressed alpha 2 and alpha 6 chains at the basal cell pole facing the basement membrane. alpha 2 also localized at sites of cell-cell contact. No staining of the epithelial component was seen with alpha 5. The polarized expression of alpha 2 and alpha 6 subunits was retained in salivary adenomas. These subunits were present at the basal cell pole of solid nests, tubules and ducts of pleomorphic adenomas, as well as of the basal layer of the epithelium of Warthin's tumor, and of the trabecular structures of basal cell adenomas. The alpha 5 subunit was consistently expressed only by cells embedded in the myxoid or chondroid matrix of pleomorphic adenomas. We conclude that the pattern of a integrin subunit expression in salivary adenomas may be related to the "epithelial" or "mesenchymal" phenotype of the neoplastic cells.

The histological spectrum of acquired nevi. An analysis of the intraepidermal melanocytic proliferation in common and dysplastic nevi.

The histological intraepidermal characteristics considered to be specific to dysplastic nevi (radial extension, lentiginous and disordered nest proliferations, cytological atypia or dyskaryosis) were investigated in a series of 114 acquired nevi showing various clinical appearances in an attempt to establish whether dysplastic nevi can be considered a homogeneous class of lesions, clearly distinct from common nevi. On the basis of the distribution of investigated architectural features, found singly or variously associated, the examined lesions were divided into 5 groups, showing an increasing incidence of dyskaryosis. Results suggest that acquired nevi, rather than two distinct classes (common and dysplastic nevi), form a histological spectrum of lesions, within which the border between lesions implying and not implying an increased melanoma risk cannot be objectively fixed.

Detection of Epstein-Barr viral genome in tumor cells of Warthin's tumor of parotid gland.

The presence of Epstein-Barr virus (EBV) DNA-sequences in specimens of Warthin's tumor in the parotid gland was studied. Using an in situ hybridization technique, EBV genome was detected in distinct cell types in routinely processed tissues. The authors' results indicated that EBV is frequently present in the cytoplasm (possibly because of a chronic, productive infection) of neoplastic cells of multiple/bilateral Warthin's tumor (MBWT) (86.7%), and only occasionally of solitary Warthin's tumor (SWT) (16.7%). In addition, EBV genome has often been documented in the cytoplasm of ductal cells (75% of MBWT and 33.3% of SWT), and occasionally of acinar cells (16.7% of both MBWT and SWT) of residual normal salivary gland tissue surrounding both MBWT and SWT. The almost constant presence of EBV DNA in tumor cells of MBWT, as opposed to the occasional finding in SWT, suggested a strong association between infection of cells with this virus and the development of multiple/bilateral lesions. The positivity of ductal epithelium supported speculations about the role of ductal cells as a histogenetic precursor of the tumor. This was the first report on the detection of EBV genome in Warthin's tumor.