Is Lobectomy Actually Worse Than Segmentectomy for All Stage I Non-Small Cell Lung Cancer?

INTRODUCTION: The recent results of the JCOG 0802 and CALGB 140503 studies suggest that segmentectomy should be considered instead of lobectomy for patients with peripheral <2 cm node-negative non-small cell lung cancer (NSCLC). This study aimed to test this hypothesis in a retrospective analysis of a larger dataset of patients with stage I NSCLC recorded in the Surveillance, Epidemiology, and End Results database. METHODS: Patients with all stage I NSCLC (≤4 cm in size) who underwent either segmentectomy or lobectomy from 2000 to 2017 were analyzed. The primary endpoints were overall survival and lung cancer-specific survival, while the secondary endpoints were the 30-day and 90-day mortality. RESULTS: Overall, 32,673 patients treated by lobectomy and 2166 patients treated by segmentectomy were included in the initial data collection. After 1:1 propensity score matching (PSM), 2016 patients in each group were enrolled in the final analysis with well-balanced baseline characteristics. After PSM, there was no difference between segmentectomy and lobectomy for all stage IA NSCLC (≤3 cm in size) in both overall survival and lung cancer-specific survival (hazard ratio: 0.87 [0.74-1.02], P value: 0.09 and hazard ratio: 0.81 [0.4-1.03], P value: 0.09, respectively). Furthermore, lobectomy had higher 30-day mortality than segmentectomy: 1.1% versus 2.1%, P value: 0.01. However, this difference was not significant for 90-day mortality, even after PSM (3.9% versus 3.0%, P value: 0.17). CONCLUSIONS: We found no evidence to support the use of lobectomy rather than segmentectomy in stage IA NSCLC in terms of either overall or lung cancer-specific long-term survival. The choice of lobectomy may also be detrimental to early postoperative recovery.

Contamination Profile of Different Formulations of Silicone Oil Tamponade Before and After Intraocular Permanence for Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to search for contaminants in silicone oil tamponades removed from eyes treated for retinal detachment, and to correlate chemical results with some clinical/functional parameters of the considered eyes. Methods: We examined a sequential cohort of eyes grouped according to the tamponade received: (1) Siluron2000 (S2), (2) RS-OIL ECS5000 (S5), and (3) Densiron Xtra (DX). Samples were collected at the beginning of the scheduled removal and analyzed by untargeted headspace gas-chromatography mass spectrometry (HS-GC-MS). Visual acuity and optic coherence tomography assessments were obtained before and after the tamponade removal. Results: Forty-one samples were analyzed: 22 belonging to the DX group, 13 to the S2 group, and 6 to the S5 group. For each group, a mixture of uninjected commercial preparation was analyzed as the reference. Different siloxanes and fluorinated compounds including perfluorodecalin (PFCL) were the most prevalent chemicals, found in 55% to 100% of the intraocular samples of the 3 groups. Some siloxanes were present also in the control matrices, whereas PFCL was only in the extracted tamponades. In the DX group, the concentration of hexamethylcyclotrisiloxane showed an inverse correlation trend with the duration of its permanence inside the eye (P = 0.054). Different alkanes, propanol, and acetaldehyde were identified only in the control matrices. Conclusions: Several contaminants including siloxanes were identified in the intraocular samples and in the control matrices. A time-related ocular uptake of some of these is conceivable. PFCL was also highly present but only in intraocular samples. Translational Relevance: After intraocular permanence silicone oils (SOs) have various unlabeled contaminants with some relevant differences with the commercial formulation chemical profile.

Relationship Between the Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) and Lung Adenocarcinoma Patterns: New Possible Insights.

INTRODUCTION: This study aimed to evaluate a potential relationship between the diffusing capacity of the lung for carbon monoxide (DLCO) and the aggressiveness of lung adenocarcinoma (ADC). METHODS: Patients who underwent radical surgery for lung ADC between 2001 and 2018 were retrospectively reviewed. DLCO values were dichotomized into DLCOlow (<80% of predicted) and DLCOnormal (≥80%). Relationships between DLCO and ADC histopathological features, clinical features, as well as with overall survival (OS), were evaluated. RESULTS: Four-hundred and sixty patients were enrolled, of which 193 (42%) were included in the DLCOlow group. DLCOlow was associated with smoking status, low FEV1, micropapillary and solid ADC, tumour grade 3, high tumour lymphoid infiltrate and presence of tumour desmoplasia. In addition, DLCO values were higher in low-grade ADC and progressively decreased in intermediate and high-grade ADC (p=0.024). After adjusting for clinical variables, at multivariable logistic regression analysis, DLCOlow still showed a significant correlation with high lymphoid infiltrate (p=0.017), presence of desmoplasia (p=0.065), tumour grade 3 (p=0.062), micropapillary and solid ADC subtypes (p=0.008). To exclude the association between non-smokers and well-differentiated ADC, the relationship between DLCO and histopathological ADC patterns was confirmed in the subset of 377 former and current smokers (p=0.021). At univariate analysis, gender, DLCO, FEV1, ADC histotype, tumour grade, stage, pleural invasion, tumour necrosis, tumour desmoplasia, lymphatic and blood invasion were significantly related with OS. At multivariate analysis, only gender (p<0.001), tumour stage (p<0.001) and DLCO (p=0.050) were significantly related with the OS. CONCLUSIONS: We found a relationship between DLCO and ADC patterns as well as with tumour grade, tumour lymphoid infiltrate and desmoplasia, suggesting that lung damage may be associated with tumour aggressiveness.

Light- and drug-induced pupillary dynamics in eyes with a retropupillary iris-claw intraocular lens.

PURPOSE: We evaluated the pupillary characteristics and response to light and drugs in eyes with posterior chamber (PC) placement of iris-claw intraocular lens (IC-IOL). METHODS: In this cross-sectional, comparative study, we included adults with an IC-IOL implanted in the PC of a single eye. We excluded patients with ocular trauma, postoperative IC-IOL displacement or complications, and extended iris atrophy. We used anterior segment optical coherence tomography to perform light-controlled pupillography, measure the pupil diameter (PD), and estimated the pupil circularity under mesopic conditions. PD was also assessed under photopic, scotopic, pharmacological mydriasis, and miosis conditions. The results were compared to those of the fellow eye, phakic, or regular pseudophakic. RESULTS: The IC-IOL and control groups included 30 eyes each. The most frequent reasons for IC-IOL implantation were complicated cataract (37%) and dislocated/luxated prior IOL (33%). Compared to the control group, the IC-IOL group had lower visual acuity, a smaller PD under scotopic conditions (p = 0.0010) and after pharmacological mydriasis (p < 0.0001), and a larger PD after pharmacological miosis (p < 0.0001). Mesopic pupil circularity was comparable between the groups. We also considered ongoing extraocular treatments with possible effects on iris motility. CONCLUSIONS: The pupillary size and profile were similar between the groups in mesopic light. Reduced mydriasis was noted in response to light and drugs, while the degree of miosis was reduced in response to inducing drugs in the IC-IOL compared to the control group. This study complements previous results concerning the PC placement of IC-IOLs by adding original observations on drug-induced pupil motility.

Cataract progression following lens-sparing pars plana vitrectomy for rhegmatogenous retinal detachment.

Lens-sparing pars plana vitrectomy (PPV) is often followed by cataract development. However, there have been few prospective studies evaluating the timing of cataract progression and potential associated factors. This was an observational study conducted at the Ophthalmology Unit of the University Hospital of Parma (Parma, Italy). Patients presenting with rhegmatogenous retinal detachment (RRD), who underwent PPV with preservation of the lens, were examined according to a scheduled follow-up (3, 6 and 12 months after PPV) and then preoperatively when cataract extraction surgery (CES) was indicated, or at the end of the study follow-up period (May 2021). The primary outcome was the interval between PPV and CES indication (based on predefined refractive criteria). A total of 36 eyes of 36 patients (mean age: 52 ± 10 years) were included in the study. Nineteen eyes (53%) were indicated for CES a median of 14.5 months (IQR: 12.0-24.8) after PPV. The nuclear and posterior subcapsular forms of cataract progressed significantly starting at 6 months after PPV. Older age at the time of PPV, silicone oil tamponade and RRD without macular involvement were significantly and independently associated with an earlier indication for CES. Patient age and the use of silicone oil tamponade must be taken into consideration when evaluating the risk of cataract development after PPV.

Tilt and decentration of posterior and anterior iris-claw intraocular lenses: a pilot study using anterior segment optical coherence tomography.

BACKGROUND: Information on the centration and tilt of iris-claw intraocular lenses (IC-IOLs) is limited. In this study, we tested the capacity of an anterior segment optical coherence tomography (AS-OCT) instrument to measure decentration and tilt of anterior and posterior IC-IOLs through an integrated software. METHODS: The present observational, cross-sectional study was conducted at University Eye Clinic of Parma (Parma, Italy). The CASIA2 swept-source AS-OCT (Tomey Corp.) was used to measure the tilt and decentration of posterior and anterior IC-IOLs in patients implanted at least 6 months in advance. After failure with full-automation, semi-manual IOL tracing was applied. In-the-bag (IB) contralateral IOLs, when present, were measured automatically. The Bland-Altman method was used to evaluate the agreement between repeated measurements (2 images for each study eye). The amount and direction of tilt and decentration were recorded and plotted into polar charts for evaluation. RESULTS: A total of 21 patients were included: 14 with posterior and 7 with anterior IC-IOL fixation. In 17 eyes (81%), the AS-OCT provided a repeatable measurement of tilt and decentration. All contralateral eyes with IB IOL were automatically measured. The median decentration was 0.67 mm, 0.24 mm, and 0.24 mm in posterior IC-IOLs, anterior IC-IOLs, and IB IOLs group, respectively. The median tilt was 5.0°, 5.6°, and 5.6° for posterior IC-IOLs, anterior IC-IOLs, and IB IOLs, respectively. Tilt direction was mainly temporal, while decentration was inferior-temporal with posterior IC-IOLs and scattered with anterior IC-IOLs and IB IOLs. CONCLUSIONS: The semi-manual tracing function of the CASIA2 AS-OCT provides repeatable and affordable measurements of the decentration and tilt of IC-IOLs in both the anterior and posterior chamber. Data from the former group were similar to the IB group.

The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios.

Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.

Multiple primary malignancies involving lung cancer: a single-center experience.

OBJECTIVE: Currently, unlike earlier years, patients affected by multiple primary malignancies (MPM) are significantly increased, thus representing a clinical-pathologic category worthy of attention. Their clinical features and prognosis still need to be studied thoroughly, and this is the aim of our study. METHODS: Patients with MPM involving lung cancer admitted in our center between January 2006 and December 2016 were considered. Parametric and nonparametric testing was used for statistical comparisons. Univariate and multivariate analysis was used to evaluate the variables associated with a prognostic value. RESULTS: MPM incidence was 19.8%. Among the 222 patients with MPM enrolled, 204 (91.8%) had two malignancies, while 18 (8.2%) had three malignancies, 38 (17.1%) were synchronous, 41 (18.5%) had lung cancer first (LCF) and 181 (81.5%) had other cancer first (OCF). A significant difference between the time of first cancer diagnosis to the second cancer diagnosis in the LCF vs OCF group was found (median 32 vs 51 months; p-value: 0.038). The most frequent anatomical sites of malignancies preceding or following lung cancer were prostate, colorectal, bladder, and larynx. Multivariate analysis revealed that sex, histologic pattern, and time and order of occurrence were independent factors for overall survival, with male sex, squamous cell lung carcinoma, synchronous and LCF MPM significantly associated with poorer overall survival. CONCLUSIONS: Prostate, colorectal, bladder, and larynx were the most frequent anatomical sites of malignancies preceding or following lung cancer. Male sex, squamous cell lung carcinoma, synchronous and LCF MPM might be associated with poorer prognosis.

Prognostic value of [18F]FDG PET/CT parameters in surgically resected primary lung adenocarcinoma: a single-center experience.

OBJECTIVE: To evaluate the prognostic role of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) measured by FDG-positron emission tomography (PET)/computed tomography (CT) in patients with primary lung adenocarcinoma undergoing surgical resection. METHODS: All consecutive patients undergoing curative surgery for primary lung adenocarcinoma at the Thoracic Surgery Unit of the University Hospital of Parma between January 2009 and December 2014 were retrospectively analyzed. The cutoff point of each continuous PET parameter was determined through receiver operating characteristic curve and Youden index, using overall survival (OS) as the classification status. Univariate and multivariate Cox proportional hazards models were applied to evaluate the association between OS and potential prognostic variables, including SUVmax, MTV, and TLG. RESULTS: A total of 193 patients were considered eligible for this study. The mean 5-year OS rate was 70.5 ± 3.5%. Acinar and lepidic patterns were more frequently associated with absent or low (<2.5) SUVmax values [18F]FDG uptake. At univariate analysis, male sex, advanced stage, micropapillary and solid pattern, lymphatic, blood vessels and pleural invasion, high SUVmax, MTV, and TLG were significantly associated with poorer OS. Multivariate analyses revealed that only sex, stage, and TLG were independent factors for OS, with male sex, stage 3+4, and high TLG value (p = 0.041) significantly associated with poorer OS. CONCLUSIONS: In this study, [18F]FDG PET/CT parameters SUVmax, MTV, and TLG were prognostic factors in patients with surgically resected lung adenocarcinoma, able to predict OS and helping to further stratify these patients into prognostic subsets. Elevated TLG was also an independent predictor for shorter OS.

Gastrointestinal Stromal Tumors: a single Center retrospective 15 years study.

BACKGROUND: Gastro Intestinal Stromal Tumors (GISTs) are defined as mesenchymal tumours that develop within the wall of the gastrointestinal tract. Surgery is the treatment of choice and may be indicated for locally advanced or previously non resectable disease after a favorable response to preoperative therapy with tyrosine kinase inhibitors. METHODS: A retrospective analysis was conducted for all patients with a confirmed or suspected diagnosis of GIST who were admitted to the University Hospital of Parma from January 2000 to January 2015.The following parameters were reviewed and analyzed: age, sex, blood type, symptoms on presentation, tumor site, tumor size, mitotic rate, risk grade, histopathology and immunohistochemistry assays, type of cells. RESULTS: All patients underwent elective surgery. Between January 2000 and January 2015, 61 patients were admitted to the OU General Surgery and Organ Transplantation, University Hospital of Parma and received surgical treatment for GISTs. Thirty-five were male (57.4%) and 26 female (42.6%). The mean age at diagnosis was 69.03 ± 10.07 years (range 29 - 89 years); males 69.6 ± 9.3 years (range 49 - 89 years) and females 68 ± 12.4 years (range 29 - 86 years). Larger tumor size, higher mitotic rate, higher risk rate, margin status contributed to poorer outcome (lower OS and DFS) as independent factors. CONCLUSIONS: Radical surgery is the treatment of choice for resectable GISTs. Very low and low-risk tumor can be treated with surgery alone. KEY WORDS: Gastrointestinal Stromal Tumor, Margin Status, Overall Survival, Tumor size.

The IGF system and cytokine interactions and relationships with longitudinal growth in prepubertal patients with cystic fibrosis.

OBJECTIVE: Growth delay is a feature of patients with cystic fibrosis (CF). CF is a condition characterized by chronic inflammation that has been shown to modify the IGF system, which is essential for normal growth, and is related to pulmonary function in CF patients. We aimed to verify whether circulating levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, insulin and the IGF system were related and/or had relationships with linear growth in children with CF. DESIGN AND PATIENTS: Seventeen prepubertal CF patients (nine males and eight females) in a stable clinical condition were enrolled. Auxological parameters, pulmonary function and the Shwachman-Kulczycki (S-K) score were assessed, and serum samples were drawn at baseline and after 12 months. MEASUREMENTS: TNF-alpha, IL-6, IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and insulin were assayed using specific commercial kits. RESULTS: At baseline, TNF-alpha serum concentration was related to serum IGF-I concentration (R = 0.53), IGF-II bioactivity (IGF-II/IGFBP-3 molar ratio, R = +0.52) and insulin concentration (R = +0.63). Changes in serum IL-6 and IGFBP-2 concentrations during the 12-month observation were positively correlated (R = +0.63). Changes in height standard deviation score (Ht SDS) were correlated with IGF-I serum concentrations at baseline (R =+0.67) and after 12 months (R = +0.70), with IGF-I bioavailability and with IGFBP-1 serum concentrations (R = -0.88). Body mass index (BMI) SDS correlated with IGF bioavailability. CONCLUSIONS: This study showed a relationship between inflammatory status and the IGF system, and an effect of these interactions on longitudinal growth. Moreover, a role for insulin in growth was identified. Better control of inflammation and preservation of insulin secretion could benefit these patients.

Changes and relationships of IGFS and IGFBPS and cytokines in coeliac disease at diagnosis and on gluten-free diet.

OBJECTIVE: To evaluate changes and relationships of IGFs and IGFBPs, serum interleukin 6 (IL-6) and tumour necrosis factor (TNF)-alpha, and auxological parameters at diagnosis of coeliac disease (CD) and at 6 months and 12 months after starting a gluten-free diet (GFD), compared with a control population. PATIENTS: Twenty patients were enrolled at diagnosis (9 male, 11 female; age 9.6 +/- 0.8 years). A healthy population of 18 subjects (5 male, 13 female; age 11.3 +/- 0.6 years) comparable for age, sex and pubertal status served as controls at baseline. MEASUREMENTS: Blood samples were taken at diagnosis, and at 6 months and 12 months after starting the GFD. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were measured using commercial kits. Height (Ht) standard deviation score (SDS), body mass index (BMI) SDS and Ht velocity SDS were evaluated at diagnosis and at 6 months and 12 months after starting GFD. RESULTS: In CD patients, both Ht SDS and BMI SDS increased during the first year of treatment, and Ht velocity SDS increased during the second 6 months of follow-up (P < 0.05). At diagnosis, IGF-I, IGF-II and IGFBP-3 were lower compared with controls, IGFBP-1 was similar, IGFBP-2, IL-6 and TNF-alpha were higher (P < 0.05). When on GFD, all peptides normalized and IGFBP-1 decreased. The IGF-I/IGFBP-2 and IGF-I/IGFBP-3 molar ratios were significantly reduced at diagnosis compared with those of controls, but were increased for both groups when on GFD. Although there was no apparent abnormality at diagnosis, the IGF-II/IGFBP-2 molar ratio increased significantly on GFD. Ht velocity SDS was positively correlated with IGFBP-3 (P < 0.05) and with the IGF-I/IGFBP-2 molar ratio (P < 0.05). Serum IL-6 was negatively correlated with IGF-I and positively with IGFBP-1 (P < 0.05). CONCLUSIONS: The data obtained from this study confirm changes in the IGF and cytokine systems at diagnosis of CD which tend to normalize on the gluten-free diet. The two systems show relationships with each other and with linear growth.