Clinical significance of postoperative complications after pancreatic surgery in time-to-complication and length of postoperative hospital stay: a retrospective study.

PURPOSE: We retrospectively analyzed pancreatectomy patients and examined the occurrence rate and timing of postoperative complications (time-to-complication; TTC) and their impact on the length of postoperative hospital stay (POHS) to clarify their characteristics, provide appropriate postoperative management, and improve short-term outcomes in the future. METHODS: A total of 227 patients, composed of 118 pancreaticoduodenectomy (PD) and 109 distal pancreatectomy (DP) cases, were analyzed. We examined the frequency of occurrence, TTC, and POHS of each type of postoperative complication, and these were analyzed for each surgical procedure. Complications of the Clavien-Dindo (CD) classification Grade II or higher were considered clinically significant. RESULTS: Clinically significant complications were observed in 70.3% and 36.7% of the patients with PD and DP, respectively. Complications occurred at a median of 10 days in patients with PD and 6 days in patients with DP. Postoperative pancreatic fistula (POPF) occurred approximately 7 days postoperatively in both groups. For the POHS, in cases without significant postoperative complications (CD ≤ I), it was approximately 22 days for PD and 11 days for DP. In contrast, when any complications occurred, POHS increased to 30 days for PD and 19 days for DP (each with additional 8 days), respectively. In particular, POPF prolonged the hospital stay by approximately 11 days for both procedures. CONCLUSION: Each postoperative complication after pancreatectomy has its own characteristics in terms of the frequency of occurrence, TTC, and impact on POHS. A correct understanding of these factors will enable timely therapeutic intervention and improve short-term outcomes after pancreatectomy.

Nivolumab-induced radiation recall pneumonitis in non-small-cell lung cancer patients with thoracic radiation therapy.

The role of previous thoracic radiation therapy as a risk factor of immune-related pneumonitis is unclear. Furthermore, some patients develop radiation recall pneumonitis, which is characterized by a radiation pneumonitis-like imaging pattern with consolidation progressing within a previous radiation field. In this multicenter retrospective study, we analyzed the relationship of previous thoracic radiation therapy with immune-related pneumonitis and the characteristics of radiation recall pneumonitis. The medical records of patients with non-small-cell lung cancer who had received nivolumab between December 2015 and March 2017 at five institutions were retrospectively reviewed. Incidence, imaging patterns, clinical course, and risk factors of immune-related pneumonitis and radiation recall pneumonitis were evaluated. A total of 669 patients were evaluated, and the incidences of all-grade and grade 3 or higher immune-related pneumonitis were 8.8% and 2.6%, respectively. The incidences of immune-related pneumonitis were 13.2% (34/257) and 6.1% (25/412) in patients with and those without previous thoracic radiation therapy, respectively. A history of previous thoracic radiation therapy was associated with immune-related pneumonitis (odds ratio, 2.11; 95% confidence interval, 1.21-3.69 in multivariate analysis). Among the patients with previous thoracic radiation therapy, 6.2% (16/257) showed radiation recall pattern. This study found an increased risk of nivolumab-induced immune-related pneumonitis associated with a history of thoracic radiation therapy. Radiation recall pattern was one of the major patterns of immune-related pneumonitis among the patients with previous thoracic radiation therapy. Incidence, risk factors, and clinical outcome of radiation recall pneumonitis were elucidated.

Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas.

INTRODUCTION: Scalp angiosarcoma is a rare and aggressive cancer. Definitive radiotherapy is a treatment option for localised scalp angiosarcoma patients. Although definitive surgical resection reportedly prolongs overall survival (OS), whether initial local treatment effect affects OS when definitive radiotherapy is administered is unclear. Therefore, this study analysed whether local recurrence within 6 months of irradiation correlates with OS and cancer-specific survival (CSS). Furthermore, how local control affects patients' quality of life was investigated. MATERIALS AND METHODS: Thirty-one localised scalp angiosarcoma patients who had received definitive radiotherapy at our institution between October 2010 and July 2021 were analysed retrospectively. The most commonly used dose fractionation was 70 Gy in 35 fractions (83.9%). Local recurrence within 6 months of radiotherapy and other clinical factors were examined in univariate and subsequent multivariate analyses for correlation with OS and CSS. RESULTS: The median follow-up period was 16 months (range, 6-45 months). Local recurrence was detected in 16 patients (51.6%), 12 of whom had recurrence within 6 months. In multivariate analyses, the presence of local recurrence within 6 months of radiotherapy was significantly associated with OS and CSS (p = 0.003, 0.0001, respectively). Ten of the 16 patients with local recurrence had severe symptoms such as bleeding, pain, difficulty opening the eye and malodour. CONCLUSIONS: The initial local treatment effect was significantly associated with OS and CSS after definitive radiotherapy. Furthermore, local recurrence after radiotherapy resulted in a variety of symptoms, including bleeding and pain, which reduced the patient's quality of life.

[A Case of Delayed-Onset Acute Interstitial Nephritis following Nivolumab Treatment in a Patient with Advanced Esophagogastric Junction Cancer].

An 81-year-old man with advanced esophagogastric junction cancer with paraaortic lymph node metastasis was treated with S-1 plus oxaliplatin and nivolumab combination chemotherapy. Subsequently, conversion surgery was performed, and the patient was discharged without postoperative complications. Two months after discharge, the patient developed fever, fatigue, and anorexia. Intravenous antibiotic therapy was started; however, the symptoms did not improve. Urine biochemical tests revealed significantly elevated N-acetyl-ß-D-glucosaminidase and ß-microglobulin levels, and acute interstitial nephritis was suspected. Steroid therapy was initiated, and the patient's symptoms improved. A renal biopsy performed at the same time the nivolumab treatment was initiated led to the diagnosis of immune-related interstitial nephritis, a probable adverse event of the treatment. Although immune-related adverse events associated with immune checkpoint inhibitors are typically colitis, interstitial pneumonia, and endocrine disturbances, we observed severe interstitial nephritis in the patient. Clinicians should also consider the possible occurrence of immune-related adverse events >2 months after administering treatment.

[Two Cases of Carcinoma en Cuirasse, as Cutaneous Metastasis of Breast Cancer].

We present 2 cases of carcinoma en cuirasse, an uncommon clinical manifestation of metastatic cutaneous breast cancer. Case 1, a 70-year-old woman, presented with diffuse erythematous, indurated skin lesions that covered her entire anterior chest wall. Skin biopsy revealed tumor cells in the dermis which were ER and PgR positive and HER2 negative. CT showed pleural and pericardial effusion which led to a final diagnosis of cutaneous metastasis from breast cancer. Fulvestrant monotherapy was initiated and maintained a good clinical effect for 40 months. She died of multiple liver metastasis after 53 months from her first visit. Case 2 was a 71-year-old woman, with a 24 month history of a left breast tumor that gradually accompanied erythematous skin indurations and erosion, which spread to her entire left chest wall and contralateral breast. Following skin biopsy and CT, she was diagnosed to have triple negative breast cancer with multiple lymph node and cutaneous metastasis. After 4 cycles of EC, capecitabine was administrated and her skin lesions improved rapidly, including the lymph nodes. She is currently alive after 12 months since her first visit and under chemotherapy against new cutaneous metastasis.

Physical Restraints in Critically Ill Children: A Multicenter Longitudinal Point Prevalence Study.

OBJECTIVES: We elucidate to investigate the prevalence of and factors associated with the use of physical restraints among critically ill or injured children in PICUs. DESIGN: This was a multicenter, longitudinal point prevalence study. SETTING: We included 26 PICUs in Japan. PATIENTS: Included children were 1 month to 10 years old. We screened all admitted patients in the PICUs on three study dates (in March, June, and September 2019). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We collected prevalence and demographic characteristics of critically ill or injured children with physical restraints, as well as details of physical restraints, including indications and treatments provided. A total of 398 children were screened in the participating PICUs on the three data collection dates. The prevalence of children with physical restraints was 53% (211/398). Wrist restraint bands were the most frequently used means (55%, 117/211) for potential contingent events. The adjusted odds of using physical restraint in patients 1-2 years old was 2.3 (95% CI, 1.3-4.0) compared with children less than 1 year old. When looking at the individual hospital effect, units without a prespecified practice policy for physical restraints management or those with more than 10 beds were more likely to use physical restraints. CONCLUSIONS: The prevalence of physical restraints in critically ill or injured children was high, and significant variation was observed among PICUs. Our study findings suggested that patient age, unit size, and practice policy of physical restraint could be associated with more frequent use of physical restraints.

Combined inhibition of PD-1/PD-L1, Lag-3, and Tim-3 axes augments antitumor immunity in gastric cancer-T cell coculture models.

BACKGROUND: Immunotherapy targeting PD-1 provides a limited survival benefit in patients with unresectable advanced or recurrent gastric cancer (GC). Beside PD-L1, the expression of inhibitory ligands such as CEACAM-1 and LSECtin on GC cells account for this limitation. Here we assessed their expression and immune suppressive effect in GC patients. METHODS: Using multiplexed immunohistochemistry staining, we evaluated the distribution of different inhibitory ligands, including PD-L1, CEACAM-1, LSECtin, and MHC class II, in 365 GC patients. We analyzed their correlations and overall survival (OS) based on the expression of each inhibitory ligand and the independent prognostic factors that affect OS. Subsequently, we evaluated the additive effect of anti-PD-1 mAb or anti-PD-L1 mAb with/without anti-Lag-3 mAb with/without anti-Tim-3 mAb in cytotoxic assay using tumor-antigen specific CTL clones against GC cell lines. RESULTS: Co-expression of the inhibitory ligands for PD-1, Tim-3, and Lag-3 was observed in the largest proportion (34.7%). CEACAM-1, LSECtin, and MHC class II expression showed significant correlation with PD-L1 expression and OS. Multivariable analysis demonstrated that CEACAM-1 low is an independent prognostic factor. Furthermore, combining dual and triple ICIs yielded additive effect on cytotoxicity of CTL clones against each immune inhibitory ligand positive GC cell lines. CONCLUSIONS: Our findings suggested that the expression of inhibitory ligands for Tim-3 and Lag-3 on GC cells serve as potential biomarkers to predict the response to anti-PD-1 therapy and the combinatorial immunotherapy with ICIs targeting for PD-1, Tim-3, and Lag-3 has a therapeutic potential for GC patients.

Immune suppression caused by PD-L2 expression on tumor cells in gastric cancer.

BACKGROUND: Gastric cancer (GC) patients with PD-L1-negative tumor occasionally have a favorable response to anti-PD-1 mAb. The aim of the present study was to investigate the regulatory mechanism and immunosuppressive role of PD-L2 in GC. METHODS: We used immunohistochemistry to evaluate the expression of PD-L2 in primary tumors from 194 patients with GC. The mechanism of PD-L2 expression was assessed in TCGA stomach adenocarcinoma tissue dataset and in vitro assay using GC cell lines. The immunosuppressive role of PD-L2 was evaluated by cytotoxicity of CTL clone against PD-L2 expressing GC cells. RESULTS: PD-L2 was expressed on tumor cells (TCs) of 28.4% patients and PD-L2 expression on TCs was significantly associated with tumor progression. TCGA dataset revealed that IFN-γ and, to a lesser extent, IL-4 signature significantly correlated with PD-L2 expression. In vitro assay showed that IFN-γ and, also to a lesser extent, IL-4 can upregulate PD-L2 expression on GC cells. Anti-PD-L2 mAb significantly enhanced the cytotoxicity of CTL clone against GC cell lines expressing PD-L2. CONCLUSIONS: PD-L2 is expressed on GC cells and PD-1/PD-L2 interaction are functionally involved in anti-tumor CTL activities. PD-L2 expression should be considered when determining the optimal immunotherapy for GC.

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BACKGROUND: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation. CASE PRESENTATION: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation. CONCLUSIONS: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.

A hybrid technique of intracavitary and interstitial brachytherapy for locally advanced cervical cancer: initial outcomes of a single-institute experience.

BACKGROUND: Locally advanced uterine cervical cancer (LAUCC) with lateral tumor extension may not always be covered adequately by conventional intracavitary brachytherapy (ICBT). Hybrid intracavitary and interstitial brachytherapy (HBT) seems to be an effective alternative by improving anatomy-oriented dose optimisation. The purpose of this study was to report initial clinical result for LAUCC treated by HBT. METHODS: Between January 2012 and November 2015, 42 patients with LAUCC (T1b2-4a) were treated with primary radiation therapy including HBT. Patients with distant metastasis other than para-aortic lymph node spread were excluded from this study. A retrospective analysis was performed for toxicity evaluation and oncological outcome calculation. RESULTS: Median follow-up was 23.2 months (range 13.2-71.4). Two-year overall survival, progression free survival, and local control rate were 81.6, 54.4, and 80.2%, respectively. Seven patients experienced local recurrence (16.6%). Of those, five were confined to the uterus and two at the parametria. Late adverse events ≥ grade 3 were seen in 3 patients. CONCLUSIONS: HBT can generate favorable local control in tumors which cannot be adequately covered by ICBT.

[The Mechanism of PD-L1 Expression and the Development of Biomarker of Anti-PD-1/Anti-PD-L1 Monoclonal Antibody from the Viewpoint of IFN-γ].

Recently, immune checkpoint inhibitors(ICI)has been developed rapidly as a novel cancer therapy. In particular, the number of worldwide clinical trials using anti-PD-1/anti-PD-L1monoclonal antibodies(mAb)are ongoing in various types of cancer. On the other hands, the response rate of anti-PD-1/anti-PD-L1 mAb monotherapy has been around 10-40% in various types of cancer, therefore, the development of biomarker for them are urgently needed. The following conditions in the tumor microenvironment are necessary for anti-PD-1/anti-PD-L1mAb therapy; the coexpression of HLA class Ⅰand PDL1 on tumor cells, and the existence of CTL around tumor cells. In this review, we discussed the mechanism of PD-L1 expres- sion and the development of biomarker of anti-PD-1/anti-PD-L1 mAb from the viewpoint of IFN-γ that can induce those conditions in the tumor microenvironment.

[A Case of Triple Negative Breast Cancer Successfully Treated with S-1].

A 73-year-old woman noticed a mass in her right breast about 1 year ago and consulted our hospital for an enlarged mass of about 10 cm in diameter.She was diagnosed with locally advanced triple negative breast cancer, and we initiated S-1 treatment as neoadjuvant chemotherapy.After 4 chemotherapy courses, computed tomography showed that the primary tumor had shrunk.Therefore, right mastectomy and axillary dissection were performed, and UFT was administered after surgery.She is currently alive with no recurrence 18 months after surgery.

Nedaplatin and irinotecan with concurrent thoracic radiotherapy followed by docetaxel consolidation in patients with locally advanced non-small cell lung cancer.

OBJECTIVE: We conducted a phase II study of nedaplatin (NP) and irinotecan (CPT) with concurrent thoracic radiotherapy (TRT) followed by docetaxel for locally advanced non-small cell lung cancer (NSCLC) to determine the safety and efficacy of the treatment. Patients with stage IIIA or IIIB NSCLC were treated with 3 cycles of chemotherapy comprising NP at 50 mg/m2 and CPT at 50 mg/m2 on days 1 and 8 every 4 weeks with concurrent TRT (2 Gy/day, total 66 Gy) followed by 3 cycles of docetaxel at 60 mg/m2 on day 1 every 3 weeks. CONCLUSION: Fifteen patients were registered, and 8 were able to receive the entire treatment regimen. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 1 patient, respectively, receiving NP and CPT with concurrent TRT. Major non-hematological toxicities were nausea, vomiting and fatigue. Grade 3 pneumonitis and esophagitis occurred in one patient each, and 4 patients developed febrile neutropenia. Docetaxel consolidation was associated with mild toxicities. Two patients died of late pulmonary failure 3 to 4 months after treatment completion, and the study was terminated. Twelve patients responded, and the median survival time, and the 1-year and 3-year survival rates were 39.3 months, 86.7% and 60.0%, respectively. In conclusion, NP and CPT with concurrent TRT is effective for patients with locally advanced NSCLC, but frequently induces pulmonary damage.

[Adaptation of Anti-PD-1/Anti-PD-L1 Antibody from the Viewpoint of Analysis of Tumor Microenvironment].

The response rate of anti-PD-1/anti-PD-L1antibody alone is about 20 to 30%and the development of biomarker for them is important to know their indication. Based on previous reports and our research results, we suggested that basic candidates of biomarker for anti-PD-1/anti-PD-L1antibody are the expression of PD-L1and HLA class I on cancer cells and the invasion of CD8 positive T cells in tumor microenvironment. Furthermore, in addition to these conditions, regulatory T cells and immune cells expressing PD-L1in tumor microenvironment, and microsatellite instability of cancer cells will be considered in the future.

Primary definitive radiotherapy with or without chemotherapy for squamous cell carcinoma of the temporal bone.

We aimed to evaluate the impact of concurrent chemoradiotherapy (CCRT) on the survival of patients with squamous cell carcinoma of the temporal bone. We retrospectively analyzed the data of 13 consecutive patients who were treated by definitive radiation therapy (RT) or CCRT as the initial treatment between 1999 and 2012. There were 5 patients with stage II disease, 5 with stage III, and 3 with stage IV, as classified according to the University of Pittsburgh system. Among these, 2, 4, and 3 patients, respectively, were treated by CCRT; whereas the remaining (3 patients with stage II and 1 with stage III) were treated by RT alone. Median follow-up duration was 39 months (12-106 months) in all cases, and 61.5 months (17-70 months) in censored cases. The 5-year overall survival (OS) rates were 51 % in all patients, and 40, 100, and 0 % in patients with stage II, stage III, and stage IV disease, respectively. In patients with stage II and III disease, the 5-year OS rates were 80 % in the CCRT group and 50 % in the RT-alone group. We found better prognosis in patients with stage II and III disease who were treated by CCRT. Only 2 patients treated by CCRT experienced adverse events more than grade 3, which were neutropenia and dermatitis. There was no late adverse event of bony necrosis. Our study results indicate that CCRT is safe and very effective as a first-line treatment for stage II and III squamous cell carcinoma of the temporal bone.

[Radical Chemoradiotherapy for Recurrent Esophageal Cancer after Curative Esophagectomy].

Recurrent esophageal cancer has a poor prognosis.However, we sometimes encounter cases with long-term survival after radical treatment for recurrent esophageal cancer.We perform radical chemoradiotherapy aggressively when recurrent esophageal cancer is present in a limited area and is sufficiently localized to be treated by radiation therapy.From June 2010 to December 2014, 150 patients underwent curative esophagectomy for esophageal cancer.Forty -one cases relapsed and we treated 13 of them with radical chemoradiotherapy.Complete response(CR), non-CR/non-PD, and progressive disease(PD) were observed in 5, 6, and 2 cases, respectively.The CR rate was 38.4%.The median survival time from recurrence was 500± 39.7 days, and the 1-year and 3-year survival rates were 84.6% and 28.7%, respectively. Four out of 5 CR cases were single site recurrences.The other case was multiple and regrowth of the cancer was identified 253 days after the CR.These results suggest that radical chemoradiotherapy for recurrent esophageal cancer after curative esophagectomy can achieve long time survival, especially in cases with single site lymph node recurrence.

Induction of epithelial-mesenchymal transition via activation of epidermal growth factor receptor contributes to sunitinib resistance in human renal cell carcinoma cell lines.

Sunitinib is widely used for treating renal cell carcinoma (RCC). However, some patients do not respond to treatment with this drug. We aimed to study the association between sunitinib sensitivity and epithelial-mesenchymal transition (EMT) regulation via epidermal growth factor receptor (EGFR) signaling, which is a mechanism of resistance to anticancer drugs. Three RCC cell lines (786-O, ACHN, and Caki-1) were used, and then we evaluated cell viability, EMT regulatory proteins, and signal transduction with sunitinib treatment. Cell viability of 786-O cells was maintained after treatment with sunitinib. After treatment with sunitinib, EGFR phosphorylation increased in 786-O cells, resulting in an increase in the phosphorylation of extracellular signal-regulated kinase, nuclear translocation of ß-catenin, and expression of mesenchymal markers. These results suggest that sunitinib induced EMT via activation of EGFR in 786-O cells, but not in ACHN and Caki-1 cells. Caki-1/SN cells, a resistant cell line generated by continuous exposure to sunitinib, displayed increased phosphorylation of EGFR. Cell viability in the presence of sunitinib was decreased by erlotinib, as the selective inhibitor of EGFR, treatment in 786-O and Caki-1/SN cells. Similarly, erlotinib suppressed sunitinib-induced EGFR activation and upregulated mesenchymal markers. Thus, we postulate that resistance to sunitinib in RCC may be associated with EMT caused by activation of EGFR.

Definitive radiotherapy for early-stage hypopharyngeal squamous cell carcinoma.

The present study analyzed the outcomes of patients with early-stage hypopharyngeal squamous cell carcinoma (HPSCC) treated with radical radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). We retrospectively reviewed the clinical records of 33 patients with early-stage HPSCC who underwent RT or CCRT between January 1999 and December 2011. Of the 33 patients who were treated, 12 had Stage I and 21 had Stage II disease. Patients with Stage I were typically treated with RT, while patients with Stage II were treated with CCRT (concurrent chemotherapy: 5FU, cisplatin or TS-1). The median follow-up period was 81 months, ranging from 15 to 155 months. The 5-year overall survival rates, cause specific survival rates, locoregional control rates, and progression-free survival rates were 58, 75, 56, and 49 %, respectively. Of the 33 patients, 51 % experienced second primary malignancies. Esophageal carcinoma occurred in several cases, and was diagnosed either during screening after treatment for the second primary malignancy or simultaneously with the second primary malignancy. Advanced-stage second malignancies significantly influenced the survival of the patients and the control rate for HPSCC. Treatment emphasizing the quality of life after treatment is needed, if a poor prognosis is expected because of advanced-stage second primary malignancy.

Down-regulation of ABCB1 in Everolimus-resistant Renal Cell Carcinoma Cells.

BACKGROUND/AIM: Everolimus-resistant Caki/EV and 786/EV cells have been established from human derived renal cell carcinoma cells, Caki-2 and 786-O, respectively. These cells exhibit resistance to everolimus and to other mTOR inhibitors and erlotinib. However, the sensitivity of these resistant cells to classical and cytotoxic anticancer drugs remain unclear. The aim of the study was to examine sensitivity of Caki/EV and 786/EV cells to classical and cytotoxic anticancer drugs. MATERIALS AND METHODS: Sensitivity to classical and cytotoxic anticancer drugs in Caki/EV and 786/EV cells was evaluated using the WST-1 (tetrazolium salts) colorimetric assay and was compared to those of the corresponding parental cells. The mRNA expression levels were measured using SYBR® green based quantitative reverse transcription-polymerase chain reaction. RESULTS: Sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin, etoposide, SN-38 (active metabolite of irinotecan), 5-fluorouracil, cisplatin, and carboplatin varied in the resistant cells. Sensitivity to carboplatin and SN-38 was comparable between resistant cells and their parental cells, whereas sensitivity to vinca alkaloids, etoposide, 5-fluorouracil, and cisplatin decreased in the resistant cells. However, sensitivity to paclitaxel and doxorubicin was remarkably enhanced in both resistant cells compared to that of parental cells, this could be partially explained by down-regulation of ABCB1 mRNA expression. CONCLUSION: The everolimus-resistant Caki/EV and 786/EV cells showed cross-resistance to classical and cytotoxic anticancer drugs. However, Caki/EV and 786/EV cells exhibited a remarkable increase in sensitivity to paclitaxel and doxorubicin, and ABCB1 mRNA was down-regulated in response to long-term exposure to everolimus.

Three Cases of Chemical Burns Caused Due to Dimethyl Sulfate Poisoning.

Dimethyl sulfate (DMS) is a drug widely used as a pharmaceutical and synthetic raw material. On the other hand, it is highly toxic and requires management and treatment as a hazardous substance. A mass outbreak of chemical burns resulting from DMS poisoning occurred at a drug factory. All three patients were brought to our hospital, a tertiary emergency medical facility, several hours after exposure. Their vital signs were stable, with only eye pain and a sore throat. However, after admission, two patients required emergency tracheostomy or endotracheal intubation due to laryngeal edema. Improvement was achieved through the administration of steroids, but a severely injured patient required an extended treatment period. DMS poisoning is rare; however, it can be fatal depending on the exposure concentration. Furthermore, even if the initial symptoms are mild, laryngeal edema may develop later, requiring careful monitoring and appropriate airway interventions.