A comparative analysis of temperature trends at Modena Geophysical Observatory and Mount Cimone Observatory, Italy

Global warming has become a critical environmental, social, and economic threat, with increasing frequency and intensity of extreme weather events. This study aims to analyse temperature trends and climate indices in the Po Valley, a significant economic and agricultural region in Italy, by examining data from two historical stations: the urban Modena Observatory and the rural Mount Cimone Observatory. The analysis extends previous studies to 2018, assessing the magnitude of climate changes since the 1950s and isolating the Urban Heat Island (UHI) effect in Modena. Significant warming trends were confirmed at both sites, with in maximum (TX) and minimum (TN) temperatures trends nearly doubling from 1981 to 2018 compared to 1951–2018. For example, TX trends reached 0.84°C·decade−1 in Modena and 0.62°C·decade−1 at Mount Cimone, while TN trends were 0.77 and 0.80°C·decade−1, respectively. Extreme climate indices showed a substantial increase in warm days and nights (TX90p and TN90p, respectively). Particularly we found TX90p of 27.5 days·decade−1 in Modena and 15 days·decade−1 at Mount Cimone while TN90p of 29.5 days·decade−1 in Modena, 22 days·decade−1 at Mount Cimone. The UHI effect significantly impacts Modena's temperature trends. Urbanization contributes up to 65% of the rise in warm nights. Specifically, frost days decreased by 1.88 days·decade−1 (37% of Urban Contribute, UC), tropical nights increased by 5.16 days·decade−1 (57% UC), warm nights increased by 12.7 days·decade−1 (65% UC), and cool nights decreased by 3.19 days·decade−1 (39% UC). Overall, the study underscores the importance of considering both global and local factors in regional climate trend analysis

Impact of routine videothoracoscopy as the first step of the planned resectiona for lung cancer. Experience of 1306 cases

We have analyzed our experience of 1306 patients with NSCLC, submitted from November 1991 to December 2007 to routine videothoracoscopy exploration, as the first step of the planned procedure, in order to evaluate its validity in obtaining precise assessment of tumor extension, verifying thoracoscopic resectability and in decreasing the rate of unnecessary thoracotomies. Thoracoscopy revealed inoperability in 58 patients (4.4%) mostly due to pleural dissemination (2.4%) or mediastinal infiltration (1.7%). Of the remaining 1248 (95.6%), 449 (34.4%) had thoracoscopic resection (230 lobectomies, 6 pneumonectomies, 230 wedge resections), 767 (58.7%) underwent open resection (592 lobectomies, 175 pneumonectomies), and 32 (2.4%) had an exploratory thoracotomy (ET). Among the 32 ETs, thoracoscopy had suspected unresectability in 7 (0.5%), had been incompletely carried out in 4 early cases (0.3%) and had been unfeasible in 21 (1.6%). In our previous series from 1980 to 1991 the E.T. rate had been 11.6%. In the present series, after the introduction of routine thoracoscopy, the E.T. rate is 2.4% and the global rate of patients correctly staged, by thoracoscopy is 73.3%, significantly better than by CT. Video exploration resulted highly reliable in excluding conditions of unresectability with a negative predictive value (NPV) of 0.97. We conclude that preliminary thoracoscopy is useful in obtaining correct staging, reliably evaluates resectability of the lesion and helps in decreasing unnecessary thoracotomies

Routine surgical videothoracoscopy as the first step of the planned resection for lung cancer

Objectives Notwithstanding preoperative staging, a number of procedures still end in an exploratory thoracotomy as a result of unexpected findings. The aim of this work is to evaluate the validity of routine videothoracoscopy, performed as the first step of every planned resection for non–small cell lung cancer, to assess tumor resectability and feasibility of the resection through thoracoscopy. Methods and Results From November 1991 to December 2007, in our department, 1306 patients with non–small cell lung cancer, judged operable at conventional staging, underwent videothoracoscopy before the operation. Thoracoscopy revealed inoperability in 58 (4.4%) patients, mostly owing to pleural dissemination (2.5%) or mediastinal infiltration (1.7%). In the remaining 1248 (95.6%), thoracoscopy did not reveal inoperability. Of these, 449 (34.4%) underwent thoracoscopic resection. The other 799 (61.2%) underwent thoracotomy: 767 underwent resection, but 32 (2.5%) had an exploratory thoracotomy. Thoracoscopy had suggested unresectability in 7 (0.5%) patients, had been incompletely carried out in 4 (0.3%), and was unfeasible in 21 (1.6%) owing to insurmountable technical reasons. In our previous series from 1980 to 1991 the exploratory thoracotomy rate had been 11.6%. In the present series, after the introduction of routine thoracoscopy in the staging process, the exploratory thoracotomy rate was 2.5%. Thoracoscopy was reliable in excluding unresectability (negative predictive value 0.97). The global percentage of correct staging was significantly better (P < .0001) by thoracoscopy (73.3%) than by computed tomography (48.7%). Considering T descriptor, video-assisted thoracic surgery correctly matched with final pathologic staging in 96.2% of patients. Conclusions Routine preliminary videothoracoscopy ensured assessment of tumor resectability and feasibility of the resection through thoracoscopy and limited unnecessary thoracotomies

Retained PTEN Expression Preferentially Identifies Mismatch Repair-Proficient Breast Cancers

Introduction/ Background Loss of phosphatase and tensin homolog (PTEN) expression and alterations in mismatch repair (MMR) genes are regarded as early oncogenic events in breast cancer. It has recently been hypothesized that the polyadenosine tract in PTEN might be a target for mutation in MMR-deficient endometrial tumors. However, the frequency and significance of MMR alterations in breast cancer is debated, and their relationship with PTEN status has not been investigated in the breast. Aims In this study, we sought to explore the relationships between PTEN expression and MMR alterations and to define whether PTEN immunohistochemistry is a predictor of MMR status in breast cancer. Methods 309 cases, including 261 invasive ductal carcinomas, no special type, 32 invasive lobular carcinomas, and 16 invasive ductal carcinomas, mixed types, carefully characterized from clinical and pathological standpoints, were reviewed and used to construct 11 tissue microarrays (TMAs). For each case, a mean of 4.5 tumor tissue cores (range 3 to 6 cores) was sampled, incorporating distinct topographic areas of the tumor, as well as matched non-neoplastic breast tissue, and, when present, associated in situ carcinoma. Taken together, 1381 spots were generated. Each TMA was subjected to immunohistochemical analysis of PTEN and the DNA MMR proteins MLH1, MSH2, MSH6 and PMS2. In order to allow a quick navigation within each TMA, and to minimize human-related biases, each stained slide was digitalized and blindly analyzed by two pathologists using a dedicated software able to segment TMA cores. The pattern of expression was therefore annotated manually on a digital database using a specific add-on module. Results According to clinicopathologic surrogate definition of intrinsic subtypes, PTEN protein loss was more frequent in luminal A-like and triple negative groups compared to luminal B-like carcinomas, as recently observed in other studies. MMR status in Luminal B-like tumors did not differ significantly between PTEN-retained and PTEN-loss groups, regardless HER2 amplification. In particular, retained PTEN expression was a predictor of MMR proficiency in approximately 35% of cases for this group. However, in luminal A-like and triple negative breast cancer groups, retained positive expression of MMR proteins was observed in 100% of cases showing PTEN wild-type immunohistochemical expression. Discussion: The present study is the first to investigate PTEN protein loss in a large set of breast carcinomas based on DNA MMR status by immunohistochemistry. Our findings broaden the understanding of the biology underpinning breast cancer, suggesting that MMR alterations are likely to be independent of PTEN status in the majority of luminal B-like breast cancers and that, in a way akin to endometrial carcinoma, MMR deficiency could play a part in the development of PTEN alterations in luminal A-like and triple negative breast cancers. The integration of traditional pathology with cutting-edge digital tools allowed a rapid quantification of immunohistochemistry and effective data organization in this wide cohort multi-variable study. Conclusion: PTEN immunohistochemistry is a useful adjunct in the clinical evaluation of breast cancer patients, being able to capture all MMR-proficient luminal A-like and triple negative tumors

Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab

Breast cancer related lymphedema (BCRL) is frequent but strategies for an individualized risk assessment are lacking. We aimed to define whether tumor-specific pathological features, coupled with clinical and therapeutic data, could help identify patients at risk. Data from 368 patients with node-positive breast cancers were retrospectively collected, including 75 patients with BCRL (0.4\u207b25.6 years follow-up). BCRL was assessed during the standard follow-up oncology visits using the circumferential measurement. Clinicopathologic and therapeutic factors associated with BCRL were integrated into a Cox proportional hazards regression model. Lymphovascular invasion (LVI) was more common in BCRL patients (n = 33, 44% vs. n = 85, 29%, p = 0.01), akin extra nodal extension (ENE) of the metastasis (n = 57, 76% vs. n = 180, 61%, p = 0.02). Sentinel lymph node excision without axillary dissection and extra-axillary radiotherapy were BCRL-unrelated. A higher number of BCRL-positive patients were treated with taxane-based chemotherapy with or without trastuzumab, compared to BCRL-negative patients (p < 0.01). Treatment with trastuzumab and/or taxanes, adjusted for systemic infections, laterality, therapy, and pathological features (i.e., LVI and ENE), had a significant impact in BCRL-free survival (p < 0.01). This work offers new insights on BCRL risk stratification, where the integration of clinical, therapeutic, and tumor-specific pathological data suggests a possible role of anti-human epidermal growth factor receptor 2 (HER2) therapy in BCRL pathogenesis

Mismatch Repair Protein Loss as a Prognostic and Predictive Biomarker in Breast Cancers Regardless of Microsatellite Instability

BackgroundBreast cancers that harbor mismatch-repair (MMR) deficiency and/or microsatellite instability (MSI) might be sensitive to immune checkpoint blockade, but there are currently no specific guidelines for assessing MMR status in breast cancer. Here, we sought to define the clinical value of MMR immunohistochemistry (IHC) and MSI analysis in breast cancers.MethodsWe subjected 444 breast cancers to MMR IHC and MSI analysis. Cases were classified as MMR-proficient (pMMR), MMR-deficient (dMMR), and MMR-heterogeneous (hMMR) based on the loss of immunoreactivity; MSI was defined by instability in the five indicators recommended by the National Cancer Institute for endometrial and colorectal cancers. Correlation of MMR status with patients\u2019 survival was assessed using the Kaplan-Meier estimator. Statistical tests were two-sided.ResultsLoss of MMR proteins was homogeneous (dMMR) in 75 patients (17%) and heterogeneous (hMMR) in 55 (12%). Among luminal breast cancers, there were similar frequencies of dMMR and hMMR tumors. Overall, the rate of discrepancy between IHC and MSI analysis was high (91%). Women with Luminal B-like dMMR carcinomas (n\u2009=\u200944) showed shorter overall survival (median\u2009=\u200977\u2009months, range\u2009=\u20090\u2013115\u2009months) than those with pMMR (n\u2009=\u2009205) or hMMR (n\u2009=\u200935) tumors (median\u2009=\u200984\u2009months, range\u2009=\u20090\u2013127\u2009months) (P\u2009=\u2009.008). On the contrary, patients with estrogen receptor-negative breast cancers treated with chemotherapy lived longer in cases of dMMR (n\u2009=\u20099) than pMMR (n\u2009=\u200933) or hMMR (n\u2009=\u20097) tumors, with 87\u2009months of median survival (range\u2009=\u200973\u2013123\u2009months) for the former compared with 79\u2009months (range\u2009=\u20098\u2013113\u2009months) for the latter two categories (P\u2009<\u2009.001).ConclusionsImmunohistochemistry and MSI are not interchangeable tests in breast carcinomas. MMR protein loss is a more common event than MSI and shows intra-tumor heterogeneity. MMR IHC allows the identification of clinically relevant subclasses of breast cancer patients, provided that multiple areas of the tumor are analyzed