Pulmonary sclerosing pneumocytoma: A pre and intraoperative diagnostic challenge. report of two cases and review of the literature

Pulmonary sclerosing pneumocytoma is a rare benign pulmonary tumor of primitive epithelial origin. Because of the unspecific radiological features mimicking malignancies and its histological heterogeneity, the differential diagnosis with adenocarcinoma and carcinoid tumors is still challenging. We report our experience of two cases of sclerosing pneumocytoma, as well as a review of the literature. Immunohistochemical findings showed intense staining of the cuboidal epithelial cells for cytokeratin-pool and TTF-1, with focal positivity for progesterone receptors. Round and spindle cells expressed positivity for vimentin, TTF-1 and focally for the progesterone receptor. Cytologic diagnosis of pulmonary pneumocytoma requires the identification of its dual cell population, made up of abundant stromal cells and fewer surface cells. Since the pre-and intraoperative diagnosis should guide surgical decision making, obtaining a sufficient specimen size to find representative material in the cell block is of paramount importance

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting. PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series. Overall, 18 studies were included in our analysis. In studies reporting “per patient” tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0–46.0%), and the pooled ORR was 80.6% (95%CI 68.7–90.1%). Regarding “per lesion” response, the pooled CR was 53.5% (95%CI 42.1–64.7%) and the pooled ORR was 77.0% (95%CI 56.0–92.6%). One-year LC rate was 80%, and 1-year OS was 67–86.2%. Pain (24.2–92.0%) and erythema (16.6–42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis. ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1–74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97–100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples

10 The adoption of sentinel node mapping with or without backup lymphadenectomy in endometrial cancer

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Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BACKGROUND We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research