Sessile serrated adenoma (SSA), also referred to as sessile serrated polyp, has been proposed as a precursor lesion to microsatellite unstable carcinoma. However, the mechanism of stepwise progression from SSA to early invasive carcinoma has been unclear. The purpose of this study was to elucidate the histologic characteristics and possible role of p53, β-catenin, BRAF, KRAS, and PIK3CA in the development and progression of SSA. We analyzed 12 cases of SSA with neoplastic progression (SSAN), including 7 cases of intraepithelial high-grade dysplasia (HGD) and 5 cases of submucosal invasive carcinoma, and compared them with 53 SSAs and 66 hyperplastic polyps (HPs) by immunohistochemistry and gene mutation analysis. Histologically, 75% (9 of 12) of SSANs showed tubular or tubulovillous growth patterns rather than serrated ones in the HGD/intramucosal carcinoma component. All 5 SSANs with invasive carcinoma lost their serrated structure and developed increased extracellular mucin in their submucosal carcinoma component, a consistent feature of mucinous adenocarcinoma. Nuclear accumulations of β-catenin and p53 were observed in 50% (6 of 12) and 41.7% (5 of 12) of SSANs, respectively, and were exclusively present in HGD/carcinoma areas. By contrast, neither nuclear β-catenin nor p53 expressions were seen in HPs or SSAs (P<0.0001). BRAF mutations (V600E) were observed in 45.8% (11 of 24) of HPs, 60.9% (14 of 23) of SSAs, and 63.6% (7 of 11) of SSANs, and were equally found in both SSA and carcinoma/HGD areas of the individual SSANs. KRAS exon 1 mutations were uncommon in all 3 groups (4.2%, 4.4%, and 0%, respectively). No mutations of PIK3CA exon 9 or exon 20 were found in any cases that were examined. These findings suggest that BRAF mutations may be associated with the pathogenesis of SSA, but progression to HGD or early invasive carcinoma may be associated with other factors, such as alterations of p53 and β-catenin. In addition, our histologic observations suggest a possible close association between SSAN and mucinous adenocarcinoma.

BackgroundThe risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD.MethodsWe retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy. The existence of ILD in these patients was determined by lung computed tomography findings; 26 patients had ILD. We evaluated the efficacy of nivolumab by measuring the response rate (RR), progression‐free survival (PFS) duration, and lung toxicity by incidence, severity, and outcome of nivolumab‐related ILD.ResultsThe RR and median PFS of the ILD and non‐ILD groups were 27% versus 13% (P = 0.078) and 2.7 (95% confidence interval [CI], 1.7–5.3) versus 2.9 months (95% CI 2.1–3.4; P = 0.919), respectively. The incidences of total and severe nivolumab‐related pneumonitis were significantly higher in the ILD group than in the non‐ILD group (31% vs. 12%, P = 0.014 and 19% vs. 5%, P = 0.022, respectively). No death from nivolumab‐related pneumonitis occurred. Over 50% of the patients in both groups with nivolumab‐related pneumonitis showed improvement over time.ConclusionRelative to the non‐ILD group, nivolumab‐related pneumonitis was observed more frequently in the ILD group; however, most cases were manageable.

Recently, cancer immunotherapy by immune checkpoint inhibitors has been considered one of the pillars for the treatment of cancer. Nivolumab is the first immune checkpoint inhibitor approved for lung cancer treatment in Japan. Although nivolumab has superior survival benefits and fewer adverse events than cytotoxic agents, it can generate dysimmune toxicities, known as immune-related adverse events. Although autoimmune manifestations are well-known immune-related adverse events, the development of infectious diseases is rare. Here, we report on a patient with advanced NSCLC in whom pulmonary tuberculosis developed rapidly during nivolumab treatment and discuss the potential mechanisms as well as what is known about infections during checkpoint inhibitor therapy.

Cancer immunotherapy using immune checkpoint inhibitors has received a remarkable amount of attention in patients with non-small cell lung cancer (NSCLC). The unique adverse effects known as immunerelated adverse events (irAEs) associated with immune checkpoint inhibitors are not known however, and neither is the incidence of infectious disease among patients receiving immune checkpoint inhibitors. The aims of this study were to investigate the incidence of infections during nivolumab treatment, and the risk factors associated with infections. Methods: We retrospectively reviewed NSCLC patients who received nivolumab in two teaching hospitals

GI-LMSs have distinctive clinicopathological and immunohistochemical features and exhibit aggressive biological behaviour.

Patients with cavitary lesions require immediate treatment for sputum culture conversion and to improve their chances of survival.

This study suggested that retreatment with anti-PD-1 antibody is a reasonable option for selected NSCLC patients.

Spontaneous vasoconstriction of suburothelial venules appears to result upon Ca(2+) release from the sarcoplasmic reticulum upon activation of inositol 1,4,5-trisphosphate receptors. This Ca(2+) opens Ca(2+) activated Cl(-) channels to trigger action potentials and Ca(2+) influx through L-type Ca(2+) channels. Adjacent perivascular interstitial cells may also have a role in generating this spontaneous venular vasoconstriction. In contrast, sympathetic nerve released noradrenaline acts on α(1A)-adrenoceptors to constrict suburothelial arterioles.