Potential efficacy of local therapy for progressive lesions after nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

International Journal of Clinical Oncology - In recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), local therapy (LT) such as surgery or radiotherapy can be treatment...     

Genetic variations predicting progression with docetaxel and novel androgen-receptor pathway inhibitors

Genetic variations represented by single-nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration-resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.     

Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas

The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer-related genes in these lesions. One hundred and seven non-ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal-type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric-type tumors (2 pyloric gland adenomas and 5 intramucosal adenocarcinomas), were investigated. Using bisulfite pyrosequencing, we assessed the methylation status of CpG island methylator phenotype (CIMP) markers and MLH1. Then using next-generation sequencing, we performed targeted exome sequence analysis within 75 cancer-related genes in 102 lesions. There were significant differences in the clinicopathological and molecular variables between small intestinal- and gastric-type tumors, which suggests the presence of at least two separate carcinogenic pathways in non-ampullary duodenal adenocarcinomas. The prevalence of CIMP-positive lesions was higher in intramucosal adenocarcinomas than in adenomas. Thus, concurrent hypermethylation of multiple CpG islands is likely associated with development of non-ampullary duodenal intramucosal adenocarcinomas. Mutation analysis showed that APC was the most frequently mutated gene in these lesions (56/102; 55%), followed by KRAS (13/102; 13%), LRP1B (10/102; 10%), GNAS (8/102; 8%), ERBB3 (7/102; 7%), and RNF43 (6/102; 6%). Additionally, the high prevalence of diffuse or focal nuclear β -catenin accumulation (87/102; 85%) as well as mutations of WNT pathway components (60/102; 59%) indicates the importance of WNT signaling to the initiation of duodenal adenomas. The higher than previously reported frequency of APC gene mutations in small bowel adenocarcinomas as well as the difference in the APC mutation distributions between small intestinal-type adenomas and intramucosal adenocarcinomas may indicate that the adenoma–carcinoma sequence has only limited involvement in duodenal carcinogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.     

Laparoscopic resection of a dumbbell‐shaped lipoma extending through the obturator foramen: A case report

Lipomas are often lightweight and small in size with few subjective symptoms. Giant lipomas are uncommon. We herein report a case involving a giant, deep‐seated dumbbell‐shaped intermuscular lipoma in the right thigh that extended into the pelvic region through the obturator foramen and caused obturator neuropathy. A 64‐year‐old man with numbness while walking was diagnosed with a 17 × 16‐cm lipomatous tumor. He underwent radical surgery performed by a multidisciplinary team consisting of orthopedic and colorectal surgeons. High‐definition magnified laparoscopic images of the deep pelvis confirmed that tumor had infiltrated the obturator nerve. The tumor was completely resected with the obturator nerve. Six months after surgical resection, the patient had no gait disturbance or evidence of recurrence. The laparoscopic approach for this kind of complicated deep pelvic surgery was safe and feasible when performed by colorectal surgeon with ample knowledge of the pelvic anatomy.     

Granulocyte colony stimulating factor-producing lung cancer with severe anemia of inflammation

Granulocyte colony stimulating factor (G-CSF)-producing lung cancer occasionally induces severe inflammation with an abnormally high white blood cell count. Herein, we report a 49-year-old man who suffered from resectable G-CSF-producing non-small cell lung cancer with continuous fever and severe anemia. Red blood cell transfusion was necessary for the anemia of inflammation. The patient underwent complete surgical tumor resection. The histopathological diagnosis was a pleomorphic carcinoma at pathological stage IIB. This is apparently the first successful case of surgical resection of G-CSF-producing lung cancer in a patient with severe anemia and uncontrollable fever.     

Biphenyl-induced cytotoxicity is mediated by an increase in intracellular Zn2+

Biphenyl is found both in natural and anthropogenic sources and is used as a fungistat in the packaging of citrus fruits. Acute exposure to high levels of biphenyl has been observed to cause skin irritation and toxic effects on the liver and kidneys. However, the mechanisms of cytotoxicity induced by biphenyl are not yet well understood. In the present study, the cytotoxicity of biphenyl was studied by flow cytometry with fluorescent probes. Biphenyl at 100?μM significantly increased cell lethality after 3?h in rat thymocytes. In addition, biphenyl at 100?μM or more elevated intracellular Zn²⁺ levels. N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), an intracellular and extracellular Zn²⁺ chelator, but not diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid (DTPA), a membrane-impermeable Zn²⁺ chelator, attenuated the biphenyl-induced increase in intracellular Zn²⁺ levels and cell death. These results suggested that biphenyl-induced cytotoxicity caused an increase in intracellular Zn²⁺ levels, which was dependent on internal Zn²⁺. Moreover, biphenyl led to an increase in sensitivity to oxidative stress, while TPEN inhibited this biphenyl-induced increase. Our findings revealed that biphenyl caused an increase in the intracellular free Zn²⁺ concentration, inducing cytotoxicity, cell death, and an increase in sensitivity to oxidative stress.     

Complete suppression of paroxysmal nonkinesigenic dyskinesia by globus pallidus internus pallidal stimulation.

Stereotactic functional surgery is being explored as potential therapies for medically intractable paroxysmal dyskinesias (PxD). We report on a 59-year-old man in whom stimulation of globus pallidus internus produced immediate and sustained relief of paroxysmal non-kinesigenic dyskinesia secondary to a rotator cuff tears on the left shoulder. Our finding strongly suggests that altered function of neuronal circuits of the basal ganglia underlies the manifestation of PxD.     

Contrast enhancement with GD-EOB-DTPA in MR imaging of hepatocellular carcinoma in mice: A comparison with superparamagnetic iron oxide

The purpose of this study was to evaluate the ability of the new liver-specific magnetic resonance contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) to detect hepatocellular carcinoma (HCC). Seventeen mice with 66 chemically induced HCCs underwent magnetic resonance imaging with both Gd-EOB-DTPA (30 μmol/kg) and superparamagnetic iron oxide (SPIO; 10 μmol/kg). After enhancement, lesion-to-liver contrast-to-noise ratios (CNRs) of 47 detected HCCs increased negatively from 3.7 ± 10.7 (mean ± SD) to –55.1 ± 25.8 with Gd-EOB-DTPA (P < .001) and increased positively from 10.4 ± 10.4 to 26.1 ± 16.3 with SPIO (P < .001). The improvement of CNR after administration of SPIO was less in smaller lesions (< 4 mm), whereas that after administration of Gd-EOB-DTPA was independent of lesion size. However, Gd-EOB-DTPA positively enhanced four HCCs (8.5%), both highly differentiated (grade 1) and moderately differentiated (grade 2). Gd-EOB-DTPA allows the conspicuous detection of small HCCs; however, moderately differentiated HCCs occasionally may be positively enhanced.