Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Genome-wide expression of the residual lung reacting to experimental Pneumonectomy.

BACKGROUND: Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). RESULTS: Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of "Extrinsic apoptotic signaling pathway" (FDR q = 7.60 × 10- 3) and "Response to insulin" (FDR q = 7.60 × 10- 3) genes, along with an enrichment of genes involved as "Negative regulators of DDX58/IFIH1 signaling" (FDR q = 7.50 × 10- 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. CONCLUSION: This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical-pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.

Is Myotomy Plus Diverticulopexy Suitable for Symptomatic Zenker's Diverticula?

The aim of the study was to prospectively evaluate the outcome of myotomy plus diverticulopexy over short and long-terms. A prospectively collected consecutive series (2007-2017) of 37 patients undergoing myotomy plus diverticulopexy was analyzed for clinical condition, operative information, peri-operative events, and follow-up by means of interview and physical examination. Diverticulopexy was scheduled regardless of the diverticulum's features and patient condition, other than operability. There was no choice or selection between possible treatment options. Patients were evaluated pre-operatively, at post-operative day 30 and after 1 year. Follow-up aimed at assessing the subjective condition following treatment. During the interview, patients were asked to self-assess their ability to swallow before and after surgery. No patient had peri-operative events, complications associated with the procedure, wound infection or impaired swallowing. All patients could start drinking the day after operation, could return to solid diet on post-operative day 2 and be discharged on post-operative days 3-4. Barium swallowing was not necessary before discharge. Full solid diet was resumed according to patient's compliance from post-operative day 2 (some patients refused solid diet soon after the operation even if asymptomatic). Follow-up ranged between 1 and 8 years. No patient was lost at follow-up. No disease recurrence was observed. Finally, no patient needed or sought for a clinical examination between the follow-up calls. Patients reported at least 50% improvement of symptomatology after 1 year. Diverticulopexy appears to be clinically safe, methodologically reproducible, and an effective procedure; it avoids suturing and offers good outcome results along with high patient satisfaction.

Stage-related outcome for thymic epithelial tumours.

BACKGROUND: Thymic epithelial tumours (TETs) are characterized by a wide variety of biological behaviors. Radical resection and stage are strong prognostic factors. Aim of this study is to review our Single Center Experience. METHODS: One hundred and seventy-seven patients observed in the period from January 2000 to December 2016 were included in the study. Data regarding clinicopathologic features, treatment, and survival were collected. Stage-related clinical standpoints and therapeutic options were also evaluated. RESULTS: Non-surgical treatment was primarily performed in 15 (8.47%), unresectable disease was intraoperatively found in 12 cases (7.4%). The analysis of 150 patients undergoing curative surgery revealed 70 stage I TET (46.66%), 49 stage II (32.66%), 19 stage III (12.66%), 6 stage IVa (4%) and 6 stage IVb (4%) at the first hospital admission. Histology identified 12 A thymoma (8%), 38 AB (25.33%), 24 B1 (16%), 50 B2 (33.33%), 19 B3 (12.66%) and 7 carcinomas (4.66%). The mean follow up time was 84.14 months (sd = 61.68 months). Disease relapse occurred in 13 patients (8.78%) at a mean period of 78.85 months (sd = 60.87 months) after surgery. Exitus due to thymoma happened in 6 cases (4.05%) after a mean survival of 56.02 months (sd = 25.17 months). The 5-year overall survival rate was 0.94 (95%CI 0.88-0.97) and the 5-year disease-free survival rate was 0.90 (95%CI 0.83-0.94). The 5-year overall survival rates were 96.1% (95% CI, 89.9-98.5%) for the early stages and 87.4% (95% CI, 65.6-95.8%) for the advanced stages (p = 0.670). The 5-year disease-free survival rates resulted being 98.8% (95% CI, 92.3-99.8%) for the early stages and 59.8% (95% CI, 37.8-76.2%) for the advanced stages (p < 0.001). CONCLUSIONS: Advanced stage TETs are characterized by higher mortality and recurrence rates. Although technically demanding, surgery, as part of multimodality therapy, could prolong survival. Iterative surgical treatment of recurrences is a viable option for selected patients. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Perugia and Terni University Hospitals [Code T1003] and was retrospectively registered.

Erdheim-Chester disease: description of two illustrative cases involving the lung.

AIM: Erdheim-Chester disease represents a clonal systemic proliferation of histiocytes. Bone is the most common site of involvement, although almost any organ, including the lungs, can be affected. METHODS AND RESULTS: The diagnosis of Erdheim-Chester disease can be difficult, owing to its rarity and protean presentation. Correlation between clinical, radiological and histological findings is mandatory for identification of the disease. Foamy histiocytes, lacking Langerhans cell markers, represent the typical histological findings, although their absence does not rule out Erdheim-Chester disease. Identification of BRAF mutation can be helpful in making the diagnosis, and allows for the development and application of targeted therapies in this setting. CONCLUSIONS: Herein, we describe two cases presenting with lung involvement and vertebral lesions, lacking the more typical long-bone involvement. One case histologically mimicked Rosai-Dorfman disease. However, both cases harboured the pathognomonic BRAFV600E mutation.

Ex vivo pulmonary nodule detection with miniaturized ultrasound convex probes.

BACKGROUND: The intraoperative localization of small and deep pulmonary nodules is often difficult during minimally invasive thoracic surgery. We compared the performance of three miniaturized ultrasound (US) convex probes, one of which is currently used for thoracic endoscopic diagnostic procedures, for the detection of lung nodules in an ex vivo lung perfusion model. METHODS: Three porcine cardiopulmonary blocks were perfused, preserved at 4°C for 6 h and reconditioned. Lungs were randomly seeded with different patterns of echogenicity target nodules (9 water balls, 10 fat, and 11 muscles; total n = 30). Three micro-convex US probes were assessed in an open setting on the pleural surface: PROBE 1, endobronchial US 5-10 MHz; PROBE 2, laparoscopic 4-13 MHz; PROBE 3, fingertip micro-convex probe 5-10 MHz. US probes were evaluated regarding the number of nodules localized/not localized, the correlation between US and open specimen measurements, and imaging quality. RESULTS: For detecting target nodules, the sensitivity was 100% for PROBE 1, 86.6% for PROBE 2, and 78.1% for PROBE 3. A closer correlation between US and open specimen measurements of target diameter (r = 0.87; P = 0.0001) and intrapulmonary depth (r = 0.97; P = 0.0001) was calculated for PROBE 1 than for PROBES 2 and 3. The imaging quality was significantly higher for PROBE 1 than for PROBES 2 and 3 (P < 0.04). CONCLUSIONS: US examination with micro-convex probes to detect pulmonary nodules is feasible in an ex vivo lung perfusion model. PROBE 1 achieved the best performance. Clinical research with the endobronchial US micro-convex probe during minimally invasive thoracic surgery is advisable.

Pericardium matrix buttressing hinders the stapled bronchial stump healing.

BACKGROUND: Biomechanical and histological properties of stapled bronchi with and without bovine pericardial matrix plus collagen reinforcement are analyzed. MATERIALS AND METHODS: Pneumonectomy with mechanical bronchial suture was performed in the swine model. Pigs were randomly assigned to three groups: three-row staplers without reinforcement (Traditional), with reinforcement (Buttressed) and control "wild type", non-resected normal bronchus (Normal). Intraoperative test was carried for air leaks at 20/30/40 mm Hg endobronchial pressure. After 60 d, tracheobronchial specimen was harvested, stocked, and analyzed. Tensile test was performed using INSTRON 5965 loading frame machine. Maximal strain resistance value, length of elongation at rupture parameter, and stiffness coefficient (K) were evaluated. Histological analysis was performed. Sample size calculation was assessed (four per group), and the Student t-test was used to statistically evaluate differences in biomechanical variables. RESULTS: No fistula occurred. Biomechanical analysis showed that maximal strain resistance is 41.22 ± 2.11 N (Traditional), 24.53 ± 3.47 N (Buttressed), and 30.91 ± 0.29 N (Normal); elongation at rupture is 16.01 ± 1.82 mm (Traditional), 12.89 ± 0.48 mm (Buttressed), and 9.32 ± 0.11 mm (Normal). Finally, K is 2.59 ± 0.16 N/mm (Traditional), 1.91 ± 0.33 N/mm (Buttressed), and 3.32 ± 0.01 N/mm (Normal). Stumps without reinforcement proved higher resistance and length of elongation than reinforced ones. Normal bronchial tissue shows the highest stiffness coefficient. Statistical analysis produced significant values for each biomechanical feature. Group Buttressed stumps show greater thickness and a substantial inflammatory reaction with granulation tissue along the whole scar and around areas of discontinuity within the scar, not yet healed. CONCLUSIONS: Reinforcing the mechanical suture line of bronchial stump with bovine pericardial matrix plus collagen shows suboptimal biomechanical and histological characteristics compared to using the stapler alone.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PURPOSES: The aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients. METHODS: We conducted a retrospective multicenter study that including all consecutive patients (aged >75 years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed. RESULTS: Two hundred and thirty-nine patients (median age 78 years) were enrolled. Lobectomies were performed in 149 (62.3 %) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23 %, respectively; p = 0.5) or the overall survival (p = 0.1), cancer-specific survival (p = 0.3) or disease-free survival (p = 0.1). After adjusting for 1:1 propensity score matching and a matched pair analysis, the results remained unchanged. A tumor size >2 cm and pN2 disease were independent negative prognostic factors in unmatched (p = 0.01 and p = 0.0003, respectively) and matched (p = 0.02 and p = 0.005, respectively) analyses. CONCLUSIONS: High-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

Pleurodesis with Thulium Cyber Laser versus talc poudrage: a comparative experimental study.

Sclerosing fluids to achieve pleurodesis could be hardly replaced for bed-side procedures, but other devices may be successfully applied during thoracoscopy. Thulium Cyber Laser was experimented for this purpose and compared to talc poudrage. Twenty pigs underwent operative videothoracoscopy (VATS). Ten models were subjected to double-port VATS and parietal pleura photoevaporation using Thulium Cyber Laser™ (TCL) 150 W 2010 nm on the posterior third of three ribs; the pleural surface was homogeneously treated inside the target perimeter. The remaining ten pigs underwent uniportal thoracoscopy; talc poudrage was performed using the current clinical practice dosage (1 g/18 kg) with accurate talc powder spread over the whole pleural surface. All models were followed up for 60 days. Pleurodesis firmness was graded on a three-tier scale (none-moderate-firm) and site-matching topographical expectancy was evaluated. TCL produced pleurodesis in all models: 7/10 were firm and 3/10 moderate. Talc poudrage pleurodesis was firm in 4/10 and moderate in 6/10. Pleural adhesions were found exclusively in the treated area after laser treatment, while talc created a wide spectrum of effects, most commonly anarchic jagged adhesions obliterating less than 50 % of the pleural cavity (7/10), mostly declivous. The pathologist found more aggressive inflammation (sometimes severe) in the talc group. Expected localized pleurodesis was always registered in laser group (10/10), while talc poudrage was found poorly effective if consistent pleurodesis is expected in an apico-dorsal position (2/10). Laser pleurodesis appears more homogeneous, qualitatively not inferior, and topographically more predictable than talc pleurodesis. Parietal photoevaporation seems effective and the localized pleurodesis is reproducible.

Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

BACKGROUND: To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. METHODS: This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. RESULTS: Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). CONCLUSIONS: The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated.

TNF-α regulates natriuretic peptides and aquaporins in human bronchial epithelial cells BEAS-2B.

Postoperative-fluid retention is a severe complication frequently reported in patients undergoing major surgical procedures. The complex network of molecules involved in such a severe surgery-induced condition remains poorly understood. Inflammation has been proposed among the various causes of fluid retention. Since TNF-α is one of the main proinflammatory cytokine initially released after major surgery, it is reasonable to assume its involvement in fluid overload. Here, we showed that TNF-α selectively regulates key molecules involved in fluids balance, such as natriuretic peptides (NPs) and aquaporins, in human bronchial epithelial cells BEAS-2B. In particular, we found that TNF-α induced a decrease of arial natriuretic peptide, natriuretic peptide receptor-1, aquaporin-1 and aquaporin-5 and an increase of brain natriuretic peptide with a different involvement of nuclear factor-κB and mitogen-activated protein kinases signaling pathway activation. Moreover, the observed changes in NPs expression, demonstrate inflammation as an additional cause of brain natriuretic peptide elevation, adding an important piece of information in the novel area of study regarding NPs and inflammation. Finally, we suggest that inflammation is one of the mechanisms of Aquaporin-1 and aquaporin-5 expression regulation. Therefore, in this exploratory study, we speculate that TNF-α might be involved in postoperative-fluid retention related to major surgery.

Giant intrathoracic cystic schwannoma resected by video-assisted thoracoscopic surgery.

Schwannoma is a benign tumour originating from the Schwann cells. Patients can remain asymptomatic, as the onset of symptoms usually depends on the compressive effect on adjacent organs; dimensional and morphological variability increase the time for the diagnosis. We report the case of a successful surgical resection, performed by video-assisted thoracoscopic surgery, on a patient with radiological evidence of a massive cystic intrathoracic neoformation, histologically revealed to be a peculiar Schwannoma.

Massive, life-threatening hemoptysis due to localized granulomatosis with polyangiitis.

Massive hemoptysis may be related to a wide spectrum of diseases whose differential diagnosis can be challenging, also due to the medical emergency condition.We present a case of a 33-year-old woman presented to our department with sudden, life-threatening hemoptysis from unknown etiology, which required a rescue pulmonary lobectomy after resuscitation maneuvers. Histology proved to be a localized Wegener granulomatosis. Our case shows that granulomatosis should always be considered among the possible, although rarer, causes of massive hemoptysis.

Concomitant Intubation with Minimal Cuffed Tube and Rigid Bronchoscopy for Severe Tracheo-Carinal Obstruction.

BACKGROUND: Our aim was to report on the use of an innovative technique for airway management utilizing a small diameter, short-cuffed, long orotracheal tube for assisting operative rigid bronchoscopy in critical airway obstruction. METHODS: We retrospectively reviewed the clinical data of 36 patients with life-threatening critical airway stenosis submitted for rigid bronchoscopy between January 2008 and July 2021. The supporting ventilatory tube, part of the Translaryngeal Tracheostomy KIT (Fantoni method), was utilized in tandem with the rigid bronchoscope during endoscopic airway reopening. RESULTS: Indications for collateral intubation were either tumors of the trachea with near-total airway obstruction (13), or tumors of the main carina with total obstruction of one main bronchus and possible contralateral involvement (23). Preliminary dilation was necessary before tube placement in only 2/13 patients with tracheal-obstructing tumors (15.4%). No postoperative complications were reported. There was one case of an intraoperative cuff tear, with no further technical problems. CONCLUSIONS: In our experience, this innovative method proved to be safe, allowing for continuous airway control. It enabled anesthesia inhalation, use of neuromuscular blockage and reliable end-tidal CO2 monitoring, along with protection of the distal airway from blood flooding. The shorter time of the procedure was due to the lack of need for pauses to ventilate the patient.

A New Medium (HistoCold) for Surgical Specimens Preserving to Improve the Preanalytic Issues in Histopathological Samples Handling: Morphologic and Antigenic Analysis.

Introduction: The onset of precision medicine has led to the integration of traditional morphologic tissues evaluation with biochemical and molecular data for a more appropriate pathological diagnosis. The preanalytic phase and, particularly, timing of cold ischemia are crucial to guarantee high-quality biorepositories of formalin-fixed paraffin-embedded (FFPE) tissues for patients' needs and scientific research. However, delayed fixation using the gold-standard and carcinogenic fixative neutral-buffered formalin (NBF) can be a significant limitation to diagnosis and biopathological characterization. HistoCold (patented; Bio-Optica Milano S.p.A., Milano, Italy) is a nontoxic, stable, and refrigerated preservative solution for tissue handling. This study examined HistoCold's potential role in improving the preanalytic phase of the pathological diagnostic process. Materials and Methods: Breast, lung, or colorectal cancers (20, 25, and 10 cases, respectively) that were to be surgically resected were recruited between 2019 and 2021. Once specimens were surgically removed, three residual samples for each patient were first promptly immersed into HistoCold for 24, 48, and 72 hours and then FFPE. These were compared with routine specimens regarding morphologic features (hematoxylin and eosin) and tissue antigenicity (immunohistochemical stains). Results: Good concordance regarding both the morphologic characteristics of the neoplasms and their proteins expression between the routine and HistoCold handled tissues were found. The tissue handling with the solution never affected the histopathological diagnosis. Conclusions: The use of HistoCold for samples transporting is easy, allows for improving the management of cold ischemia time, and monitoring the fixation times in NBF, resulting in good quality tissue blocks for biobanking. Moreover, it could be a candidate to eliminate formalin from operating theaters. HistoCold looks very promising for the preanalytic phase of human tissues handling in the era of precision medicine, to provide the best service to patients, and to scientific research.

Therapeutic options in locally advanced thyroid carcinoma. Our experience.

INTRODUCTIONS: Thyroid cancer is the most common endocrine malignancy with an incidence equal to 1% of all malignant tumors. Prognostic factors affecting survival are manifold, including in several classifications (AMES, AGES, CORN and TNM). In this sense, the invasion of adjacent structures is one of the most important variables. The authors describe the experience of a single center in surgical treatment of advanced thyroid cancer. MATERIALS AND METHODS: Between 1986 and 2010 , 1565 patients were undergoing surgery with thyroid cancer. In particular, 1403 interventions were made for differentiated cancer, 97 for medullary carcinoma, 25 for insular carcinoma, 29 for anaplastic carcinoma, 2 for plasmacytoma, and 7 for lymphoma and 2 for angiosarcoma. Among these 896 showed invasion of adjacent structures and / or distant metastases. RESULTS: There were no perioperative deaths or major complications. Surgical procedures consisted of: 13 loboistmectomy, 519 total thyroidectomy (TT), 325 TT with lymphadenectomy of the central compartment, 7 TT with radical lymphectomy, 621 TT with functional lymphectomy, 6 TT with breast lumpectomy, 5 TT with with video-assisted lung metastasectomy, 16-TT with resection and tracheal anastomosis, 6 TT with laryngotracheal resection, 3 TT with laryngectomy, 4 TT with trachetomy, 28 TT with respiratory stent placement, 12 tracheotomy. At present, 1328 patients were free of disease, while 104 showed recurrence. Total of 133 deaths were recorded, all linked to disease relapse. DISCUSSION: The role of surgery in the treatment of advanced thyroid cancer is still undeniable. In the presence of extracapsular trespassing, in fact, the adoption of interventions demolition permits long-term survival, given the lack of aggressiveness of the tumor differentiated representing the majority of cases. The aim of surgical radicalization addition, even in the presence of distant metastases, it is justified by the possibilities offered by the therapeutic radioiodine treatment, which is not feasible in the presence of significant amounts of thyroid tissue which picks. In the presence of undifferentiated tumors, finally, endoscopic or surgical treatment may be indicated by simple purpose of palliation of respiratory symptoms.

Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid.

BACKGROUND: The clinical significance of multifocal pulmonary neuroendocrine proliferation (MNEP), including tumorlets and pulmonary neuroendocrine cell hyperplasia, in association with typical carcinoid (TC), is still debated. METHODS: We evaluated a retrospective series of TC with long-term follow-up data prospectively collected from 2 institutions and compared the outcome between TC alone and MNEP plus TC. Several baseline covariates were imbalanced between the MNEP plus TC and TC groups; therefore, we conducted 1:1 propensity score matching and inverse probability of treatment weighting in the full sample. In the matched group, the association of clinical, respiratory, and work-related factors with the group was determined through univariable and multivariable conditional logistic regression analysis. RESULTS: A total of 234 TC patients underwent surgery: 41 MNEP plus TC (17.5%) and 193 TC alone (82.5%). In the MNEP plus TC group, older age (P < .001), peripheral tumors (P = .0032), smaller tumor size (P = .011), and lymph node spread (P = .02) were observed compared with the TC group. Relapses occurred in 8 patients in the MNEP plus TC group (19.5%) and 7 in the TC group (3.6%). After matching, in 36 pairs of patients, a significantly higher 5-year progression-free rate was observed for the TC group (P < .01). Similar results were observed using inverse probability of treatment weighting in the full sample. The odds of being in the MNEP plus TC group was higher for those with work-related exposure to inhalant agents (P = .008), asthma or bronchitis (P = .002), emphysema, fibrosis, and inflammatory status (P = .032), or micronodules on the chest computed tomography scan and respiratory insufficiency (P = .036). CONCLUSIONS: The association with MNEP seems to represent a clinically and prognostic relevant factor in TC. Hence, careful preoperative workup, systematic pathologic evaluation, including nontumorous lung parenchyma, and long-term postoperative follow-up should be recommended in these patients.

Efficacy of tigecycline pleurodesis: a comparative experimental study.

BACKGROUND: We investigated whether tigecycline (TIGE) is more effective than talc in inducing pleurodesis in rabbits. METHODS: Fifty-six New Zealand rabbits were utilized in a two-phase study: Effects at 14 d (phase I) and at 28 d (phase II) were assessed. Saline solution (SAL n = 3), talc slurry (TALC 200 mg/kg, n = 5), and TIGE at different concentrations (mg/kg): TIGE0.5 (n = 5); TIGE1 (n = 5); TIGE3 (n = 5); TIGE25 (n = 5); TIGE50 (n = 5) were randomly injected, for each phase, through a right chest drainage. TIGE0.5 and TIGE1 were ineffective during phase I and were thus excluded from further investigation. At post mortem examination, pleurodesis was graded grossly and microscopically by three observers blinded to treatment groups. RESULTS: Phase I: pleurodesis was more effective in TIGE25 and TIGE50 (P < 0.001); TALC was better than TIGE0.5 (P < 0.001), and TIGE1 (P = 0.49), macroscopically. Pleural thickness was significantly higher in TIGE25 compared with SAL, TALC, TIGE0.5, TIGE1, and TIGE3 (P < 0.01). No significant differences were evident between TALC and TIGE3, both macroscopically (P = 0.90) and microscopically (inflammation P = 0.99, fibrosis P = 0.96, pleural thickness P = 0.99). Phase II: better effectiveness of TIGE50 compared with all other groups (P < 0.001) except TIGE 25 (P = 0.29); results similar to phase I for TALC and TIGE3 (P = 0.99), macroscopically. Microscopically greater inflammation in TALC compared with TIGE3 (P < 0.05) and in TIGE50 to TIGE3 (P = 0.05). Significant complications occurred in all TIGE50 group. One of TIGE25 and one of TIGE50 died of respiratory distress and of right hemothorax+ascites, respectively. CONCLUSIONS: Intrapleural TIGE3 mg/kg is as effective as talc in inducing pleurodesis in rabbits. The intrapleural TIGE toxicity threshold was reached at TIGE25 mg/kg concentration.