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The UVB irradiation is well known for its impact on the development of skin cancer. However, low UVB irradiation plays a protective role against various human diseases including cancer through its effect on tumor suppression. This article summarizes the key findings of the paper by Park et al., which describes a novel molecular mechanism of moderate UVB irradiation in suppressing the growth of melanoma and colorectal cancer. Key observations in this article are that moderate UVB irradiation can enhance tumor immunity by (1) increased infiltration of CD4+ and CD8+ T cells; (2) increased infiltration of CD103+ conventional type 1 dendritic cells (cDC1); and (3) a significant decrease of M2 tumor associate macrophages (TAMs) into the tumor. The authors further identified the role of Batf3 transcription factor in moderate UVB irradiation‐mediated anti‐tumor immune response. Deletion of Batf3 transcription factor reversed the tumor suppressive effect with decreased CD103+ cDC1 cell infiltration. This pre‐clinical study provides a very novel mechanistic insight into the utilization of moderate UVB irradiation for the management of melanoma and colorectal cancer. This study further provides the direction of new future research to explore moderate UVB irradiation in combination with checkpoint blockade antibodies to enhance immunotherapeutic response against various solid tumors. [ABSTRACT FROM AUTHOR]

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4’s transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis. [ABSTRACT FROM AUTHOR]

Sunlight exposure is a significant risk factor for UV‐induced deteriorating transformations of epidermal homeostasis leading to skin carcinogenesis. The ability of UVB radiation to cause melanoma, as well as basal and squamous cell carcinomas, makes UVB the most harmful among the three known UV ranges. UVB‐induced DNA mutations and dysregulation of signaling pathways contribute to skin cancer formation. Among various signaling pathways modulated by UVB, tyrosine phosphorylation signaling which is mediated by the action of protein tyrosine kinases (PTKs) on specific tyrosine residues is highly implicated in photocarcinogenesis. Following UVB irradiation, PTKs get activated and their downstream signaling pathways contribute to photocarcinogenesis by promoting the survival of damaged keratinocytes and increasing cell proliferation. While UVB activates oncogenic signaling pathways, it can also activate tumor suppressive signaling pathways as initial protective mechanisms to maintain epidermal homeostasis. Tyrosine dephosphorylation is one of the protective mechanisms and is mediated by the action of protein tyrosine phosphatases (PTPs). PTP can counteract UVB‐mediated PTK activation and downregulate oncogenic signaling pathways. However, PTPs have not been studied extensively in photocarcinogenesis with previous studies regarding their inactivation induced by UVB. This current review will summarize the recent progress in the protective function of PTPs in epidermal photocarcinogenesis. [ABSTRACT FROM AUTHOR]

• IASLC grading system has acceptable performance in diverse populations. • We proposed IASLC modification for increasing predictability in Korean patients. • Lepidic proportion further differentiated IASLC grade 2 patients. We aimed to measure the validity of the International Association for the Study of Lung Cancer (IASLC) grading system in Korean patients and propose a modification for an increase of its predictability, especially in grade 2 patients. From 2012 to 2017, histopathologic characteristics of 1358 patients with invasive pulmonary adenocarcinoma (stage I–III) from two institutions were retrospectively reviewed and re-classified according to the IASLC grading system. Considering the amount of the lepidic proportion, the validity of the revised model (Lepidic-10), derived from the training cohort (hospital A), was measured using the validation cohort (hospital B). Its predictability was compared to that of the IASLC system. Of the 1358 patients, 259 had a recurrence, and 189 died during follow-up. The Harrell's concordance index and area under the curve of the IASLC system were 0.685 and 0.699 for recurrence-free survival (RFS) and 0.669 and 0.679 for death, respectively. From the training cohort, the IASLC grade 2 patients were divided into grades 2a and 2b (Lepidic-10 model) with a 10 % lepidic pattern. This new model further distinguished patients in both institutions that had better performance than the IASLC grading (Hospital A, p < 0.001 for RFS and death; Hospital B, p = 0.0215 for RFS, p = 0.0429 for death). The IASLC grading system was easily applicable; its clinical use in predicting the prognosis of Korean patients with pulmonary adenocarcinoma was validated. Furthermore, the introduction of the lepidic proportion as an additional criterion to differentiate grade 2 patients improved its predictability. [ABSTRACT FROM AUTHOR]

Background: The prognosis of invasive mucinous adenocarcinoma (IMA) remains controversial and should be clarified by comparison with the International Association for the Study of Lung Cancer (IASLC) histologic grading system for invasive nonmucinous adenocarcinoma (INMA). Methods: This study included patients with IMA who underwent curative resection. Their clinicopathological outcomes were compared with those of patients with INMA. Propensity score matching was performed to compare the prognosis of IMA with IASLC grade 2 or 3. Kaplan–Meier survival curves and log‐rank tests were used to analyze recurrence‐free survival (RFS) and overall survival (OS). Results: The prognoses of IMA and IASLC grade 2 were similar in terms of RFS and OS. Although patients with IMA had better RFS than patients with IASLC grade 3, the OS was not significantly different. After propensity score matching, IMA demonstrated similar RFS to IASLC grade 2 but superior to IASLC grade 3; there was no difference in the OS compared with grades 2/3. Multivariate analysis revealed that tumor size (hazard ratio [HR] = 1.20, p = 0.028), lymphovascular invasion (HR = 127.5, p = 0.003), and maximum standardized uptake value (HR = 1.24, p = 0.005) were poor prognostic predictors for RFS. Patients with IMA demonstrated RFS similar to and significantly better than that of patients with IASLC grades 2 and 3, respectively. For OS, IMA prognosis was between that of IASLC grades 2 and 3. Conclusions: Since the prognosis of IMA among lung adenocarcinomas appears to be relatively worse, further clinical studies investigating IMA‐specific treatment and follow‐up plans are necessary to draw more inferences. [ABSTRACT FROM AUTHOR]

Purpose: Left upper mediastinal lymph node dissection (UMLND)—a technically demanding step of McKeown esophagectomy—is frequently complicated by recurrent laryngeal nerve (RLN) palsy. Under the hypothesis that robotic esophagectomy (RE) could increase the safety and feasibility of UMLND, we retrospectively investigated the degree to which a pre-existing experience in video-assisted thoracoscopic esophagectomy (VATE) may affect the learning curves of this critical part of RE. Methods: Surgeon A had previously performed > 150 VATE procedures before transitioning to RE. While surgeon B had previously assisted to 50 RE, his pre-existing VATE experience consisted of less than five procedures. A total of 103 and 76 McKeown RE procedures were performed by surgeons A and B, respectively. The learning curve of left UMLND for each surgeon was examined using the cumulative sum method. Results: The inflection point of RLN palsy for surgeon A occurred at patient 31. While the nerve palsy rate decreased from 32.3 to 4.2% (p < 0.001), the number of nodes harvested during left UMLND did not appreciably change. Surgeon B showed a bimodal learning curve for RLN palsy with primary and secondary inflection points at patients 15 and 49, respectively. The RLN palsy rate initially decreased from 66.7% (patients 1–15) to 14.7% (patients 16–49), followed by an additional decline to 3.7% (patients 50–76). However, the number of nodes harvested during left UMLND showed a downtrend which was paralleled by decreasing rates of RLN palsy. These results indicate that surgeon B has not yet reached an ideal balance between an extensive UMLND and nerve protection. Conclusion: The pre-existing VATE experience seems to affect the learning curves of left UMLND during RE. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the results of postoperative bronchopleural fistula repair and to identify adverse factors for its success. Methods: We retrospectively reviewed the surgical results of 39 patients who underwent surgical repair for postoperative bronchopleural fistula between January 2010 and June 2020. Success of bronchopleural fistula repair was defined as the visual closure of the bronchopleural fistula with the absence of an air leak, a recurrence of bronchopleural fistula and infection in the thoracic cavity. Results: Twenty‐five (64.1%) bronchopleural fistulas occurred after pulmonary resection and 14 (35.9%) after lung transplantation. Bronchopleural fistula was diagnosed 19 days (median) and repaired 28 days (median) after the initial operation by primary closure in 27 (69.2%) patients, and by additional resection in 12 (30.8%) patients. The overall success rate was 59% (23/39) and the overall mortality was 56.4% (22/39). Multivariable analysis revealed that the patients who were supported by mechanical ventilation at the time of repair had significantly lower success rates than those without (15.4%, 2/13 vs. 80.8%, 21/26, respectively, p < 0.001). The omental flap group tended to have a better success rate than the muscle flap group (p = 0.07). Conclusions: There was a high overall mortality rate after bronchopleural fistula repair and a low success rate. Mechanical ventilation at the time of bronchopleural fistula repair was significantly related to the failure of bronchopleural fistula repair. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the characteristics and pretreatment risk factors for postoperative pulmonary complications (PPCs) after neoadjuvant concurrent chemoradiotherapy (CRTx) in patients with non‐small cell lung cancer (NSCLC). Methods: We retrospectively reviewed data of 122 patients who underwent curative resection after neoadjuvant CRTx for NSCLC between 2007 and December 2019. Clinical data, including pulmonary function and body mass index (BMI) at the time of concurrent CRTx initiation, were analyzed. We performed logistic regression analyses to identify the risk factors for PPCs and built a nomogram with significant factors. Results: Of the 122 patients included (mean age, 60.1 ± 9.7 years; 69.7% male), 27 experienced PPCs (severity grade ≥ 2). The most common PPCs were pneumonia (n = 17). Patients with PPCs had a significantly longer hospital stay (median 6.0 vs. 17 days, p < 0.001) and a higher in‐hospital mortality rate (1.1% vs. 29.6%, p < 0.001). In multivariable analysis, lower BMI (odds ratio [OR] 0.796, 95% confidence interval [CI] 0.628–0.987, p = 0.038), no comorbidity (OR 0.220, 95% CI: 0.059–0.819, p = 0.048), smoking history (OR 4.362, 95% CI: 1.210–15.720, p = 0.024), and %predicted DLCO <60% (OR 3.727, 95% CI: 1.319–10.530, p = 0.013) were independent risk factors for PPCs. The predictive accuracy of the nomogram built with factors was excellent (concordance index: 0.756). Conclusions: The nomogram constructed with factors identified in multivariable analysis could serve as a reliable tool for evaluating the risk of PPCs in the patients who underwent neoadjuvant CRTx for NSCLC. [ABSTRACT FROM AUTHOR]

Background: The benefits of mediastinal lymph node dissection (MLND) in colorectal cancer‐related pulmonary metastasectomy (PM) have been poorly reported. This study aimed to determine whether MLND affects survival in patients undergoing PM and to identify the prognostic factors for survival. Methods: We retrospectively reviewed 275 patients who had undergone colorectal cancer‐related PM from January 2010 to December 2016. MLND was defined as the resection of at least six mediastinal lymph node stations according to the International Association for the Study of Lung Cancer criteria (N1, ≥3 stations; N2, ≥3 stations). The propensity score matching method was used to reduce bias. Results: Thirty‐three (12%) patients underwent MLND, and 13 (4.7%) patients had mediastinal lymph node involvement. This study showed no difference in 5‐year overall survival (no MLND, 52.7% vs. MLND, 53.5%; p = 0.81). On multivariable analysis, negative prognostic factors for overall survival were preoperative carcinoembryonic antigen (CEA) level (p < 0.001), a higher number of metastatic nodules (p < 0.001), metastatic nodule size ≥2 cm (p < 0.001), and lymph node involvement (p = 0.006). Conclusions: Mediastinal lymph node involvement, preoperative CEA level, higher metastatic nodule number, and nodule size negatively affected survival whereas MLND in PM was not associated with survival. [ABSTRACT FROM AUTHOR]