Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

<p>Abstract</p> <p>Background</p> <p>In Japan, high incidences of interstitial lung disease (ILD) and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC). We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients.</p> <p>Findings</p> <p>We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0). ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%), of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD.</p> <p>Conclusion</p> <p>The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.</p

Strategy for lung parenchyma-sparing bronchial resection: a case series report

Lung parenchyma-sparing bronchial resection is uncommon, and the operative procedure depends on the cause and location of the stenosis. We present 6 cases and discuss the different surgical strategies for sleeve resection of the central airway without lung resection. Bronchoplasty for the main bronchus and truncus intermedius was performed with a posterolateral approach. We resected the right main bronchus including the right lateral wall of the lower trachea and half of the carina obliquely and performed an anastomosis. The tumour in the left lobar bronchus was exposed and removed by transient division of the accompanying pulmonary artery. Although post-transplant stenosis and malacia can pose a challenge, bronchoplasty can be used as a definitive treatment in experienced centres

Postoperative clinical outcomes of unicompartmental knee arthroplasty in patients with isolated medial compartmental osteoarthritis following medial meniscus posterior root tear

Background: Cartilage degradation progresses rapidly following medial meniscus posterior root tear (MMPRT). Unicompartmental knee arthroplasty (UKA) has been performed for medial compartmental osteoarthritis following MMPRT. We evaluated the clinical and radiographic outcomes of UKA for medial compartmental osteoarthritis after an untreated MMPRT. Methods: Twenty-one patients who underwent UKA for isolated medial compartment osteoarthritis following MMPRT were retrospectively investigated. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score and knee range of motion. The posterior tibial slope and tibial component inclination were evaluated using plain radiographs. Results: The mean follow-up periods were 25.5 +/- 13.8 months. Clinical outcomes improved significantly postoperatively. The mean postoperative knee extension angle was-1.1 degrees +/- 2.1 degrees, and the knee flexion angle was 134.3 degrees +/- 4.9 degrees. The posterior tibial slope angle decreased from 9.0 degrees +/- 2.0 degrees preoperatively to 5.4 degrees +/- 1.8 degrees postoperatively, and postoperative tibial component inclination at the final follow-up was 2.9 degrees +/- 1.1 degrees varus. No aseptic loosening or deep infections were observed. Conclusion: UKA significantly improved clinical outcomes and could be a viable surgical option for treating isolated medial compartmental osteoarthritis accompanied by untreated MMPRT

Mice Treated with an Antibiotic Cocktail Containing Metronidazole Show Attenuated Allergy Responses through the Induction of Regulatory T Cells in the Intestinal Mucosa

This study sought to determine whether antibiotic treatments affect the pathogenesis of allergic diseases. We demonstrated that mice treated with a mixture of four antibiotic agents （ampicillin, neomycine, metronidazole, and vancomycin） showed significantly decreased antigen-specific IgE production compared to control mice, whereas mice treated with the same cocktail without metronidazole showed no change in IgE production compared to controls. Regulatory T cell suppression induced by particular antibody combinations is a possible mechanism of this effect, with an increased frequency of regulatory T cells also observed in the mesenteric lymph nodes （MLN） of mice treated with the mixture of four antibiotics, but not in the second cocktail without metronidazole. Our antibiotic treatments also dramatically decreased the diversity of mouse intestinal microbiota compared to control mice, based on 16SrRNA analysis of the cecum fecal composition. In conclusion, mice treated with antibiotic mixtures containing metronidazole, but not those treated without metronidazole, showed attenuated allergy responses and increased induction of regulatory T cells in the mucosa

Genetic Polymorphism of Cancer Susceptibility Genes and HPV Infection in Cervical Carcinogenesis

It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results

A Case of Pneumatosis Cystoides Intestinalis Mimicking Intestinal Perforation

An 85-year-old man was referred to the Department of Gastroenterological and General Surgery after complaining of abdominal pain and distention. Abdominal computed tomography (CT) revealed intra-abdominal free air, mimicking perforated peritonitis, with air collection within the jejunum bowel wall. On the basis of these findings, we made a diagnosis of pneumatosis cystoides intestinalis (PCI) with intra-abdominal free air. The PCI signs had disappeared completely by Day 7 of hospitalization. The patient was discharged from hospital after 15 days. At the time of writing, the patient’s PCI has not reappeared. This case highlights the clinical importance of PCI, and that the lung window settings of abdominal CT are useful tools to enable an accurate diagnosis of PCI

Establishment of macaque trophoblast stem cell lines derived from cynomolgus monkey blastocysts

The placenta forms a maternal-fetal junction that supports many physiological functions such as the supply of nutrition and exchange of gases and wastes. Establishing an in vitro culture model of human and non-human primate trophoblast stem/progenitor cells is important for investigating the process of early placental development and trophoblast differentiation. In this study, we have established five trophoblast stem cell (TSC) lines from cynomolgus monkey blastocysts, named macTSC #1-5. Fibroblast growth factor 4 (FGF4) enhanced proliferation of macTSCs, while other exogenous factors were not required to maintain their undifferentiated state. macTSCs showed a trophoblastic gene expression profile and trophoblast-like DNA methylation status and also exhibited differentiation capacity towards invasive trophoblast cells and multinucleated syncytia. In a xenogeneic chimera assay, these stem cells contributed to trophectoderm (TE) development in the chimeric blastocysts. macTSC are the first primate trophoblast cell lines whose proliferation is promoted by FGF4. These cell lines provide a valuable in vitro culture model to analyze the similarities and differences in placental development between human and non-human primates

Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 c risk allele in the contemporary percutaneous coronary intervention era: A prospective observational study

Hara M, Sakata Y, Nakatani D on behalf of the OACIS Investigators, et al. Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study. BMJ Open 2014;4:e005438. doi: 10.1136/bmjopen-2014-00543

Epidermal growth factor receptor (EGFR)—tyrosine kinase inhibitors as a first-line treatment for postoperative recurrent and EGFR-mutated non-small-cell lung cancer

[OBJECTIVES] To clarify survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) as first-line treatment for postoperative recurrence. [METHODS] A retrospective chart review was performed to identify consecutive patients who received EGFR-TKIs as first-line treatment for postoperative recurrence of non-small-cell lung cancer (NSCLC) harbouring EGFR gene mutations at our institution between August 2002 and October 2020. Therapeutic response, adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using the Kaplan–Meier analysis. The Cox proportional hazards model was used for univariable and multivariable analyses. [RESULTS] Sixty-four patients were included in the study. The objective response and disease control rates were 53% and 92%, respectively. Grade 3 or greater adverse events were noted in 4 (6.3%) patients, including 1 patient (1.6%) of interstitial pneumonia. The median follow-up period was 28.5 months (range 3–202 months). The total number of events was 43 for PFS and 23 for OS, respectively. The median PFS was 18 months, and the median OS was 61 months after EGFR-TKI treatment. In multivariable analysis, osimertinib showed a tendency to prolong PFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.12–1.1; P = 0.071], whereas the micropapillary component was significantly associated with shorter OS (HR 2.1, 95% CI 1.02–6.9; P = 0.045). [CONCLUSIONS] EGFR-TKIs as first-line treatment appeared to be a reasonable treatment option in selected patients with postoperative recurrent EGFR-mutated NSCLC. Osimertinib and the micropapillary component may be prognostic factors