Immune checkpoint inhibitors (ICIs) have achieved promising clinical results in cancer treatment over the past decade. However, the efficacy of ICIs is less than 30% in most tumor types, and studies are underway to identify the predictive factors responsive to ICIs. More than 1,000 species of microorganisms live in the human body, and the second human genome project, The Human Microbiome Project, has been conducted to understand human diseases through interactions with microbes. As the microbiome project has progressed, many studies have reported on the association between microorganisms and human diseases, including preclinical and clinical studies on the relationship between ICIs and the microbiome. Therefore, in this manuscript, the relationship between the microbiome and cancer, especially the effectiveness of ICIs, is reviewed.

Immune checkpoint inhibitors (ICIs) have achieved promising clinical results in cancer treatment over the past decade. However, the efficacy of ICIs is less than 30% in most tumor types, and studies are underway to identify the predictive factors responsive to ICIs. More than 1,000 species of microorganisms live in the human body, and the second human genome project, The Human Microbiome Project, has been conducted to understand human diseases through interactions with microbes. As the microbiome project has progressed, many studies have reported on the association between microorganisms and human diseases, including preclinical and clinical studies on the relationship between ICIs and the microbiome. Therefore, in this manuscript, the relationship between the microbiome and cancer, especially the effectiveness of ICIs, is reviewed.

Although most patients prefer dying at home, patients whose condition rapidly becomes critical need care in the intensive care unit (ICU), and it is rare for them to die at home with their families. Therefore, interest in hospice and palliative care for patients in the ICU is increasing. Hospice and palliative care (PC) is necessary for all patients with life-threatening diseases. The following patients need palliative care in the ICU: patients with chronic critical illnesses who need tracheostomy, percutaneous gastrostomy tube, and extracorporeal life support; patients aged 80 years or older; stage 4 cancer patients; patients with specific acute diseases with a poor prognosis (e.g., anoxic brain injury and intracerebral hemorrhage requiring mechanical ventilation); and patients for whom the attending physician expects a poor prognosis. There are two PC models—a consultative model and an integrative model—in the ICU setting. Since these two models have advantages and disadvantages, it is necessary to apply the model that best fits each hospital’s circumstances. Furthermore, interdisciplinary decision-making between the ICU care team and PC specialists should be strengthened to increase the provision of hospice and palliative care services for patients expected to have poor outcomes and their families.

A 41-year-old man presented a bean sized, solid, painless left scrotal mass he'd had for 10 years. The mass was well demarcated and it showed homogeneous echogenecity on ultrasonography. Simple mass excision was performed and the specimen revealed a relatively well circumscribed mass lesion composed of dilated tubules with flattened lining cells. A focal infiltration to the seminiferous tubule and involvement of the biopsy margins were observed. The tubules had a positive reaction to the calretinin and anti-mesothelial antibody on immunohistochemical stain. Therefore, the tumor was diagnosed as adenomatoid tumor of the testis. Adenomatoid tumors of testis are rare benign neoplasms that are thought to originate from mesothelum. Most cases were reported in the epididymis, spermatic cord and testicular tunica, and rare cases were from the ejaculatory duct, prostate and adrenal gland. The findings of adenomatoid tumor infiltrating through the testis parenchyme and seminiferous tubule, like for our case, have not been previously reported in Korea.
Adenomatoid Tumor* ; Adrenal Glands ; Adult ; Biopsy ; Calbindin 2 ; Ejaculatory Ducts ; Epididymis ; Humans ; Korea ; Male ; Prostate ; Seminiferous Tubules* ; Spermatic Cord ; Testis* ; Ultrasonography

Nocardia species are aerobic, gram-positive pathogens found worldwide in soil. Nocardia is considered an opportunistic pathogen, and its infection mostly occurs in immunocompromised patients. We report a case of Nocardia farcinica induced mediastinitis and pneumonia that occurred in a 64-year-old male patient who had no significant medical history except for hypertension. He visited another hospital with a complaint of dyspnea and left chest wall pain. The symptoms arose 7 days ago without any trauma and they worsened. A mediastinal mass was found on computed tomography scan. After being transferred to our hospital for further evaluation, he was diagnosed with mediastinitis and pneumonia. As N. farcinica was found to be the causative organism by 16S rRNA sequencing, proper antibiotic therapy including trimethoprim/sulfamethoxazole was initiated immediately. After this, the patient improved and he was discharged. If an infection has a disseminating course, nocardiosis cannot be excluded even in immunocompetent patients. Once the diagnosis is established, prompt antibiotic therapy should be performed based on the severity.
Diagnosis ; Dyspnea ; Humans ; Hypertension ; Immunocompromised Host ; Male ; Mediastinitis* ; Middle Aged ; Nocardia Infections ; Nocardia* ; Pneumonia* ; Soil ; Thoracic Wall

BACKGROUND: This study is aimed at finding out the relationship between long working hours, one of major job stress elements, and hearing impairment in unexposed workers to occupational and environmental noise. METHODS: This study was performed on 1628 regular, full-time wage workers between the age of 25-64 who indicated in the survey of having no experience of exposure to noise, normal otoscopic findings, and not suffering from diabetes based on the data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES 2010–2012). The average working hours per week was categorized into 40 h and lower group, more than 40 to 48 h group, more than 48 to 60 h group, and more than 60 h group. The groups were defined as suffering from low or high frequencies hearing impairment if the average hearing threshold for 0.5, 1, 2 kHz or 3, 4, 6 kHz in both ears exceeds 25 dB based on the pure tone audiometry. The association between average weekly working hours and hearing impairment was analyzed using logistic regression after gender stratification. RESULTS: The prevalences of low and high frequencies hearing impairment in male workers were 4.3 and 28.6 %, respectively, which were much higher than female’s prevalence of 2.7 and 11.1 %. For male workers, no significant association was found between average weekly working hours and low and high frequencies hearing impairment. For female workers, odds ratios (OR) of low and high frequencies hearing impairment were 4.22 (95 % confidence interval (CI) 1.09–16.27) and 4.49 (95 % CI 1.73–11.67), respectively, after controlling for several related factors, such as, age, Body Mass Index (BMI), socio-economic status, health-related behavioral, and occupational characteristics variables, in the final model in the group working more than 60 h compared to the group working 40 h and lower. In addition, a dose-response relationship was observed that ORs of low and high frequencies hearing impairment were increased according to increasing average weekly working hours. CONCLUSIONS: The association between long working hours and hearing impairment in both low and high frequencies was significant in Korean female workers with a dose-response relationship. Therefore, the law to change the culture of long working hours should be enacted in order to protect the workers’ health and improve the quality of life in Korean workers.
Audiometry ; Body Mass Index ; Ear ; Female ; Hearing Loss* ; Hearing* ; Humans ; Jurisprudence ; Korea* ; Logistic Models ; Male ; Noise* ; Nutrition Surveys* ; Odds Ratio ; Prevalence ; Quality of Life ; Salaries and Fringe Benefits

PURPOSE: Ipilimumab improves survival in advanced melanoma patients. However, the efficacy and safety of ipilimumab has not been evaluated in Asian melanoma patients with a high frequency of mucosal and acral melanoma subtypes. MATERIALS AND METHODS: Advanced melanoma patients treated with 3 mg/kg ipilimumab in a Korean multicenter named-patient program (NPP) were evaluated between September 2014 and July 2015. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes. RESULTS: A total of 104 advanced melanoma patients were treated. The primary sites were acral (31.7%), mucosal (26%), cutaneous (26%), uveal (9.6%), and unknown (6.7%). Sixty-eight patients (65.4%) experienced adverse events, and the most common toxicity was skin rash (22.1%), 10 patients (9.6%) experienced adverse events of grade 3 or higher. The median progression-free survival (PFS) was 2.73 months (95% confidence interval, 2.67 to 2.85), and there was no difference in PFS according to subtypes. Poor performance status, liver metastasis, and NLR (≥ 5) were independent poor prognostic factors by multivariate analysis. CONCLUSION: In the Korean NPP cohort, ipilimumab showed similar efficacy and tolerability compared to Western patients, regardless of subtypes. All subtypes should benefit from ipilimumab with consideration of performance status, liver metastasis, and NLR.
Asian Continental Ancestry Group ; Biomarkers ; Cohort Studies* ; Disease-Free Survival ; Exanthema ; Humans ; Immunotherapy ; Liver ; Lymphocytes ; Melanoma* ; Multivariate Analysis ; Neoplasm Metastasis ; Neutrophils

Purpose: For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers. Materials and Methods: To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment. Results: In the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in wellknown cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2–42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging. Conclusion Our data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier:NCT02901301).

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with mutations of the VHL tumor suppressor gene located on chromosome 3p25. The loss of functional VHL protein contributes to tumorigenesis. This condition is characterized by development of benign and malignant tumors in the central nervous system (CNS) and the internal organs, including kidney, adrenal gland, and pancreas. We herein describe the case of a 74-year-old man carrying the VHL gene mutation who was affected by simultaneous colorectal adenocarcinoma, renal clear cell carcinoma, and hemangioblastomas of CNS.
Adenocarcinoma* ; Adrenal Glands ; Aged ; Carcinogenesis ; Carcinoma, Renal Cell* ; Central Nervous System ; Colorectal Neoplasms ; Genes, Tumor Suppressor ; Hemangioblastoma* ; Humans ; Kidney ; Pancreas ; von Hippel-Lindau Disease*

PURPOSE: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. MATERIALS AND METHODS: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. RESULTS: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. CONCLUSION: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.
Adenocarcinoma ; Biomarkers ; Carcinoembryonic Antigen* ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Erlotinib Hydrochloride* ; Female ; Humans ; Keratin-19* ; Prognosis ; Receptor, Epidermal Growth Factor