Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III).

A series of optically active hypervalent iodine(III) reagents prepared from the corresponding (R)-2-(2-iodophenoxy)propanoate derivative was employed for the asymmetric dioxytosylation of styrene and its derivatives. The electrophilic addition of the hypervalent iodine(III) compound toward styrene proceeded with high enantioface selectivity to give 1-aryl-1,2-di(tosyloxy)ethane with an enantiomeric excess of 70-96% of the (S)-isomer.

Differentiation between pleomorphic adenoma and schwannoma in the parapharyngeal space: histogram analysis of apparent diffusion coefficient.

OBJECTIVES: To elucidate the differences between pleomorphic adenomas and schwannomas occurring in the parapharyngeal space by histogram analyses of apparent diffusion coefficient (ADC) values measured with diffusion-weighted MRI. METHODS: This retrospective study included 29 patients with pleomorphic adenoma and 22 patients with schwannoma arising in the parapharyngeal space or extending into the parapharyngeal space from the parotid region. Using pre-operative MR images, ADC values of tumor lesions showing the maximum diameter were measured. The regions of interest for ADC measurement were placed by contouring the tumor margin, and the histogram metrics of ADC values were compared between pleomorphic adenomas and schwannomas regarding the mean, skewness, and kurtosis by Wilcoxon's rank sum test. Subsequent to the primary analysis which included all lesions, we performed two subgroup analyses regarding b-values and magnetic field strength used for MRI. RESULTS: The mean ADC values did not show significant differences between pleomorphic adenomas and schwannomas for the primary and subgroup analyses. Schwannomas showed higher skewness (p = 0.0001) and lower kurtosis (p = 0.003) of ADC histograms compared with pleomorphic adenomas in the primary analysis. Skewness was significantly higher in schwannomas in all the subgroup analyses. Kurtosis was consistently lower in schwannomas but did not reach statistical significance in one subgroup analysis. CONCLUSIONS: Skewness and kurtosis showed significant differences between pleomorphic adenomas and schwannomas occupying the parapharyngeal space, but the mean ADC values did not. Our results suggest that the skewness and kurtosis of ADC histograms may be useful in differentiating these two parapharyngeal tumors.

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study.

BACKGROUND/AIM: Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities. PATIENTS AND METHODS: Data of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022 were analyzed. The endpoint was overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). OS and PFS were analyzed comparatively with and without irAEs, and complete response (CR) or partial response (PR), and stable disease (SD) or progressive disease (PD) were compared. RESULTS: One hundred thirty-five patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. For the pembrolizumab only group, the median OS and PFS were 22.7 and 5.1 months, respectively. There were significant differences in OS and PFS between CR or PR and SD or PD (p<0.01, p<0.01, respectively). For pembrolizumab with chemotherapy, the OS was not reached and median PFS was 7.0 months. There was a significant difference in PFS between CR or PR and SD or PD (p<0.01). There was a significant difference in PFS between patients with and without irAEs (p=0.02). CONCLUSION: The real-world therapeutic effect of pembrolizumab for R/M SCCHN was comparable to that observed in the KEYNOTE048 trial. In addition, irAEs and best overall response were considered as prognostic factors.

Head and neck small-cell carcinoma: A multicenter study of 39 cases from 10 institutions.

Objective: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. Materials and methods: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. Results: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). Conclusion: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

[Investigation of how to prevent mucositis induced by chemoradiotherapy].

Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using PA solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3. 0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44 ± 8. 0 days for the R solution group, 52 ± 18. 8 days for the P-A solution group, and 61 ± 19. 5 days for the S solution group, indicating that the R solution group significantly shortened the length of hospital stay compared to the S solution group. These results suggested that the use of an R or P-A solution may be effective in preventing oral mucositis and impaired nutrition of those undergoing chemoradiotherapy for head and neck cancer.

Influence of irradiation conditions on the deformation of pure titanium frames in laser welding.

Due to its ease of use in connecting metal frames, laser welding is now applied in dentistry. However, to achieve precise laser welding, several problems remain to be resolved. One such problem is the influence of irradiation conditions on the deformation of titanium frameworks during laser welding, which this study sought to investigate. Board-shaped pure titanium specimens were prepared with two different joint types. Two specimens were abutted against each other to form a welding block with gypsum. For welding, three different laser waveforms were used. Deformation of the specimen caused by laser welding was measured as a rise from the gypsum surface at the opposite, free end of the specimen. It was observed that specimens with a beveled edge registered a smaller deformation than specimens with a square edge. In addition, a double laser pulse waveform--whereby a supplementary laser pulse was delivered immediately after the main pulse--resulted in a smaller deformation than with a single laser pulse waveform.

Differentiation between solitary fibrous tumors and schwannomas of the head and neck: an apparent diffusion coefficient histogram analysis.

METHODS:: Our study included 5 patients with SFT and 18 patients with schwannoma in the head and neck region for whom pre-operative ADC images were obtained using either 1.5 or 3.0 T MRI system with two b-values. An ADC image that showed the tumor at the largest major diameter was selected for each patient, and a region of interest was set circumscribing the tumor. The histogram distributions of ADC values within the region of interest were compared between SFTs and schwannomas with respect to the mean, standard deviation, median, skewness, kurtosis, and percentile. RESULTS:: The mean and the median ADC values were significantly higher for schwannomas than in SFTs (p = 0.007 in both). Skewness and kurtosis of ADC histograms were significantly lower for schwannomas than for SFTs (p = 0.002 and 0.005, respectively). ADC values differed greatest between the two tumor groups at the 90th percentile, and were significantly higher for schwannomas than for SFTs (p = 0.005). On receiver operating characteristic curve analysis, the area under the curve for kurtosis, skewness, and the 90th percentile ADC values was 0.92, 0.90, and 0.90, respectively. CONCLUSIONS:: Our study suggests that skewness on ADC histograms may be the most useful diagnostic factor, followed by kurtosis and the 90th percentile ADC values, for differentiation between SFTs and schwannomas.

C3orf70 Is Involved in Neural and Neurobehavioral Development.

Neurogenesis is the process by which undifferentiated progenitor cells develop into mature and functional neurons. Defects in neurogenesis are associated with neurodevelopmental and neuropsychiatric disorders; therefore, elucidating the molecular mechanisms underlying neurogenesis can advance our understanding of the pathophysiology of these disorders and facilitate the discovery of novel therapeutic targets. In this study, we performed a comparative transcriptomic analysis to identify common targets of the proneural transcription factors Neurog1/2 and Ascl1 during neurogenesis of human and mouse stem cells. We successfully identified C3orf70 as a novel common target gene of Neurog1/2 and Ascl1 during neurogenesis. Using in situ hybridization, we demonstrated that c3orf70a and c3orf70b, two orthologs of C3orf70, were expressed in the midbrain and hindbrain of zebrafish larvae. We generated c3orf70 knockout zebrafish using CRISPR/Cas9 technology and demonstrated that loss of c3orf70 resulted in significantly decreased expression of the mature neuron markers elavl3 and eno2. We also found that expression of irx3b, a zebrafish ortholog of IRX3 and a midbrain/hindbrain marker, was significantly reduced in c3orf70 knockout zebrafish. Finally, we demonstrated that neurobehaviors related to circadian rhythm and altered light-dark conditions were significantly impaired in c3orf70 knockout zebrafish. These results suggest that C3orf70 is involved in neural and neurobehavioral development and that defects in C3orf70 may be associated with midbrain/hindbrain-related neurodevelopmental and neuropsychiatric disorders.

A case of mediastinal abscess in a hemodialysis patient.

An asymptomatic mediastinal abscess was incidentally found in a 68-year-old male patient with a long history of hemodialysis. He had never had any symptoms but complained of chest pain only after the abscess ruptured into the right thoracic cavity. The abscess was discovered incidentally, when computed tomography was performed to determine the cause of his increasing ascites. Video-assisted thoracic surgery was performed to facilitate sufficient drainage and safe debridement. After the operation, we administered adequate antibiotics and continued irrigation of the thoracic cavity. The origin of his abscess was still unknown, but we have to consider that immunocompromised patients including those undergoing hemodialysis can develop severe infectious conditions even with minor causes. This case is clinically suggestive of the need to focus on the immunocompromised condition of hemodialysis patients. Furthermore, our case reveals video-assisted thoracic surgery to be a safe and less invasive procedure for patients in poor general condition.

Long-term survival in a case of pleomorphic carcinoma with a brain metastasis.

Pleomorphic carcinoma (PC) is a rare malignant lung tumor with a poorer prognosis compared to other histological types of non-small cell lung cancer. However, several recent immunohistochemical studies revealed that a low MIB-1 index is a good prognostic marker in patients with PC. We report the case of a patient with PC and a single brain metastasis that achieved long-term recurrence-free survival following treatment with combined modality therapy. In this case, the MIB-1 index was reduced by gemcitabine-based chemotherapy, which may have led to long-term disease-free survival. The MIB-1 index may be a useful biomarker for the response to chemotherapy.

Solitary metastasis to the intercostal muscle from hepatocellular carcinoma: A case report.

INTRODUCTION: Skeletal muscle metastases from carcinomas, especially to intercostal muscles, are rare. Most metastatic chest wall tumors from hepatocellular carcinoma (HCC) result from disseminations through needle tracts of intrahepatic HCC treatments. PRESENTATION OF CASE: We report the case of a 65-year-old man with chronic viral hepatitis B whose intrahepatic lesions were stabilized by repeated radiofrequency ablations and transcatheter arterial chemoembolization. Follow-up computed tomography demonstrated a well-enhanced mass in the right chest wall. Because α-fetoprotein and des-γ-carboxy prothrombin levels were elevated and no other tumors were detected, we diagnosed the mass as an extrahepatic metastasis from the HCC and resected it along with the surrounding ribs. There was no involvement of the bone, pleura, and lung. DISCUSSION: The tumor was microscopically diagnosed as an intercostal muscle tumor metastasized from HCC, which has not been documented previously. The resection rate of extrahepatic tumors of HCC is low in literature. No other apparent extrahepatic recurrence has been observed for more than 20 months after the surgery. CONCLUSION: We report the case of HCC patient who underwent surgical resection of an intercostal muscle tumor that had metastasized from HCC. Pathological examination of the tumor revealed the tumor cells in the blood vessels, and we speculate it hematogeneous metastasis.

Resection of giant mediastinal liposarcoma using the hemiclamshell incision.

A 39-year-old woman who had experienced slight chest discomfort for a few months was referred to our hospital with an abnormal shadow on a regular checkup chest X-ray film. A computed tomography scan revealed a large well-defined mass in close relationship to the great vessels of the anterior mediastinum. Magnetic resonance imaging showed the anterior mediastinal mass, which was about 25 cm in diameter, expanding to the left pleural cavity with heterogeneous intensity. Because of the size and location of the mass, a combination of anterolateral thoracotomy and partial longitudinal median sternotomy--so-called hemiclamshell incision--was chosen, allowing excellent visualization and complete dissection of the giant tumor. The final histopathology of the resected specimen confirmed well-differentiated liposarcoma.