Surgical outcomes of video-assisted neck surgery for papillary thyroid carcinoma.

PURPOSE: New approaches to endoscopic thyroid surgery have been developed to improve cosmetic results, one of which is video-assisted neck surgery (VANS). The present study investigates the safety and effectiveness of thyroidectomy by VANS as oncologic surgery for papillary thyroid carcinoma (PTC). METHODS: The subjects of this retrospective study were 121 patients with PTC, who underwent hemi-thyroid lobectomy and central lymph node dissection via open surgery (n = 102) or VANS (n = 19) at Tokushima University Hospital between 2011 and 2023. We performed 1:1 propensity score matching and then compared the surgical outcomes between the two matched groups. RESULTS: Propensity score matching generated 18 distinct examination pairs. The VANS group had significantly less blood loss (P = 0.003), but a longer operative time (P < 0.001) than the open thyroidectomy group. There were two cases of transient recurrent laryngeal nerve paralysis and one case of recurrence in the lateral regional lymph nodes in the VANS group. However, no significant differences were observed in the incidence of complications (P = 0.243) or recurrence (P = 0.500) between the two groups. CONCLUSION: VANS is a safe and effective surgical procedure for PTC, but longer follow-up is needed to assess tumor recurrence.

Evaluation of pathogenicity of WT1 intron variants by in vitro splicing analysis.

BACKGROUND: Wilms tumor 1 (WT1; NM_024426) causes Denys-Drash syndrome, Frasier syndrome, or isolated focal segmental glomerulosclerosis. Several WT1 intron variants are pathogenic; however, the pathogenicity of some variants remains undefined. Whether a candidate variant detected in a patient is pathogenic is very important for determining the therapeutic options for the patient. METHODS: In this study, we evaluated the pathogenicity of WT1 gene intron variants with undetermined pathogenicity by comparing their splicing patterns with those of the wild-type using an in vitro splicing assay using minigenes. The three variants registered as likely disease-causing genes: Mut1 (c.1017-9 T > C(IVS5)), Mut2 (c.1355-28C > T(IVS8)), Mut3 (c.1447 + 1G > C(IVS9)), were included as subjects along the 34 splicing variants registered in the Human Gene Mutation Database (HGMD)®. RESULTS: The results showed no significant differences in splicing patterns between Mut1 or Mut2 and the wild-type; however, significant differences were observed in Mut3. CONCLUSION: We concluded that Mut1 and Mut2 do not possess pathogenicity although they were registered as likely pathogenic, whereas Mut3 exhibits pathogenicity. Our results suggest that the pathogenicity of intronic variants detected in patients should be carefully evaluated.

Silicone stent placement for tracheal stenosis induced by a giant goiter due to Graves' disease: a case report.

Background: Although thyroid tumors with tracheal stenosis are occasionally encountered, severe tracheal stenosis caused by benign thyroid tumors is rare. We herein describe a case in which a silicone tracheal stent was placed for severe tracheal stenosis induced by a giant goiter due to Graves' disease. Case Description: A 93-year-old woman had been receiving thiamazole treatment for Graves' disease with a thyroid goiter for 32 years. She emergently presented to the hospital with sudden difficulty breathing and the temporary loss of consciousness. Although marked stridor was heard, the patient's respiratory status was stable in the first visit. Computed tomography revealed a giant thyroid goiter that extended to the mediastinum. The trachea was compressed by the sternal notch and thyroid gland, resulting in severe stenosis, and the tracheal lumen was only 1 mm. Surgical thyroidectomy was expected to be difficult due to the high risk of complications associated with the large size of the goiter and advanced age of the patient. Therefore, we decided to place a tracheal stent. A silicone stent (Dumon tube®) was inserted into the site of tracheal stenosis under general anesthesia. After stent placement, respiratory distress symptoms improved, and no complications were observed. Three months after stent placement, the stent opening side was narrowed due to defective granulation and, thus, was cauterized with argon plasma coagulation. Conclusions: We encountered a patient who was treated by tracheal silicone stent placement for severe tracheal stenosis induced by a giant goiter due to Graves' disease. A silicone stent effectively secures the airway for benign thyroid tumors that cause severe airway stenosis.

New insights into the oxidation process from neutron and X-ray crystal structures of an O2-sensitive [NiFe]-hydrogenase.

[NiFe]-hydrogenase from Desulfovibrio vulgaris Miyazaki F is an O2-sensitive enzyme that is inactivated in the presence of O2 but the oxidized enzyme can recover its catalytic activity by reacting with H2 under anaerobic conditions. Here, we report the first neutron structure of [NiFe]-hydrogenase in its oxidized state, determined at a resolution of 2.20 Å. This resolution allowed us to reinvestigate the structure of the oxidized active site and to observe the positions of protons in several short hydrogen bonds. X-ray anomalous scattering data revealed that a part of the Ni ion is dissociated from the active site Ni-Fe complex and forms a new square-planar Ni complex, accompanied by rearrangement of the coordinated thiolate ligands. One of the thiolate Sγ atoms is oxidized to a sulfenate anion but remains attached to the Ni ion, which was evaluated by quantum chemical calculations. These results suggest that the square-planar complex can be generated by the attack of reactive oxygen species derived from O2, as distinct from one-electron oxidation leading to a conventional oxidized form of the Ni-Fe complex. Another major finding of this neutron structure analysis is that the Cys17S thiolate Sγ atom coordinating to the proximal Fe-S cluster forms an unusual hydrogen bond with the main-chain amide N atom of Gly19S with a distance of 3.25 Å, where the amide proton appears to be delocalized between the donor and acceptor atoms. This observation provides insight into the contribution of the coordinated thiolate ligands to the redox reaction of the Fe-S cluster.

Impact of postoperative physical activity on the development of pneumonia in the subacute phase after esophagectomy in patients with esophageal cancer: A retrospective cohort study.

PURPOSE: Physical activity is important to improve recovery following surgery. This study investigated the impact of physical activity on the development of pneumonia after radical esophagectomy in patients with thoracic esophageal cancer in the subacute phase from postoperative day 11 to hospital discharge. METHODS: This retrospective cohort study included 83 patients who underwent radical esophagectomy for esophageal cancer between 2016 and 2022. Physical activity was measured using an activity tracker, and the average number of steps between postoperative days 8 and 10 was examined. The primary outcome was pneumonia (Clavien-Dindo classification 2 or higher) developing between postoperative day 11 and hospital discharge. We used the receiver operating characteristic (ROC) curve analysis to calculate the optimal cutoff value of physical activity that can predict the development of pneumonia and define low physical activity. We used logistic regression analysis to investigate the impact of low physical activity on postoperative pneumonia. RESULTS: Pneumonia developed in 10 patients (12.0%) during the observation period. The optimal cutoff value of physical activity for predicting pneumonia was 1494 steps per day (sensitivity: 60.0%, specificity: 89.0%, area under the curve: 0.743). In multivariate analysis, low physical activity was an independent predictor of incident pneumonia [odds ratio: 12.10, 95% confidence interval: 2.21-65.90, p = 0.004], with adjustment for age, gastric tube reconstruction route, and postoperative recurrent nerve palsy. CONCLUSIONS: Physical activity following radical esophagectomy in patients with thoracic esophageal cancer was an independent predictor of the development of pneumonia in the subacute phase after radical esophagectomy.

Abscopal effect in a patient with solitary extramedullary plasmacytoma of the thyroid: case report.

Background: The abscopal effect is a systemic antitumor response that occurs distant to the irradiation site and is induced by local irradiation. We herein describe a case of solitary extramedullary plasmacytoma (SEP) of the thyroid in which bone metastases disappeared after thyroidectomy and cervical radiotherapy (RT). Case Description: A 68-year-old man with a right cervical swelling for approximately 10 years visited a hospital with left elbow pain that persisted for 5 months. He was referred to our hospital for more detailed examinations and treatment. An immobile mass of approximately 10 cm in diameter was palpable on the right side of the patient's neck. Computed tomography (CT) showed osteolytic changes in the left humerus and right scapula, and a tumor in the right lobe of the thyroid gland. The patient was diagnosed with widely invasive follicular carcinoma and multiple bone metastases and underwent total thyroidectomy. During surgery, tumor infiltration into the trachea was observed. Shaving between the tumor and trachea was performed. Based on the results of a pathological examination, the patient was diagnosed with primary extramedullary plasmacytoma of the thyroid. After surgery, external beam RT was performed on the neck, which also reduced the pain in the left elbow. Positron emission tomography (PET)-CT showed the decreased accumulation of fluorodeoxyglucose (FDG) in the left humerus and right scapula, and the amelioration of osteolytic changes on CT. Conclusions: SEP of the thyroid is rare, and to the best of our knowledge, this is the first case report in which the abscopal effect was observed after thyroidectomy and cervical RT.

A case of papillary thyroid carcinoma with renal and pulmonary metastases.

Distant metastases derived from papillary carcinoma are generally detected in the lungs and bones. However, renal metastasis is rare. We herein report a case of papillary thyroid carcinoma with renal and pulmonary metastases that had been initially diagnosed as primary renal carcinoma with pulmonary metastases. The lesions showed response to immune checkpoint inhibitors and tyrosine kinase inhibitor but not to radioactive iodine therapy.

Spontaneous esophageal perforation within a hiatal hernia: A case report.

INTRODUCTION: Spontaneous esophageal perforation, also commonly referred to as Boerhaave's syndrome, is one of the most lethal diseases causing an acute abdomen. Though rare, emergent surgical intervention is often required and management can be various based upon the site of the perforation. This literature has been written in line with the SCARE criteria (Agha et al., 2020) [1]. PRESENTATION OF CASE: A 76-year-old man presented with acute abdominal pain. Computed tomography (CT) revealed and an emergent esophagogastroduodenoscopy (EGD) was performed carefully, which revealed a 7 cm all-layer esophageal laceration in the left lower esophageal wall. In our case, a hiatal hernia was protruding into the mediastinum, and the perforation site was inside of it, but there was no invasion into the thoracic cavity, thus a transabdominal approach was performed without thoracotomy. DISCUSSION: This type of esophageal perforation within a hiatal hernia is quite rare and provides a unique clinical challenge. In addition, A review reported the average length of spontaneous esophageal perforation to be around 2 cm while our case had a perforation with a length of 7 cm. We chose the combination of the simple suture with omental buttress and wide drainage, but a complete fundoplication was impossible due to its large size of perforation. CONCLUSION: We chose the open abdominal approach because the case had high inflammation, a hiatal hernia and possibility of retro-gastric perforation. However, MIS should have been considered first if a situation or human resources allow it.

ypN0 in Patients With Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer.

BACKGROUND: Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). PATIENTS AND METHODS: A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. RESULTS: ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). CONCLUSION: ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.

Impact of preoperative 6-minute walk distance on long-term prognosis after esophagectomy in patients with esophageal cancer.

BACKGROUND: The 6-minute walk distance (6MWD) is a simple way of assessing exercise capacity. The purpose of this study was to investigate the relationship between preoperative 6MWD and long-term prognosis after esophagectomy. METHODS: This retrospective cohort study involved 108 patients who underwent radical esophagectomy for esophageal cancer between 2013 and 2020. The patients were classified into the short group (SG: 6MWD < 480 m) or the long group (LG: 6MWD ≥ 480 m). To adjust for the background characteristics of both groups, propensity score matching (PSM) analysis was performed and 32 patients were matched from each group. Five-year overall survival (OS) and relapse-free survival (RFS) were analyzed by the Kaplan-Meier method. The log-rank test was used to evaluate differences in survival between the groups. After adjusting for other prognostic factors, the Cox proportional hazards model was used to investigate the impact of preoperative 6MWD on long-term prognosis. RESULTS: The median follow-up period was 923 days. Thirty-three deaths were recorded during the study period. After PSM, 5-year OS following surgery was 29.2 and 66.1% (p = 0.003) and 5-year RFS was 27.9 and 58.6% (p = 0.021) in the SG and LG, respectively. In Cox proportional hazards analysis, the SG was a significant independent risk factor for OS (hazard ratio 3.33; 95% confidence interval 1.37-8.11, p = 0.008) and RFS (hazard ratio 2.30; 95% confidence interval 1.08-4.88, p = 0.030). CONCLUSION: The preoperative 6MWD is useful for evaluating exercise capacity and predicting the long-term outcome in patients undergoing esophagectomy.

A CASE OF VAGUS NERVE SCHWANNOMA DIFFICULT TO DISTINGUISH FROM LYMPH NODAL METASTASIS OF ESOPHAGEAL CANCER.

In this report, we describe a rare case of vagus nerve schwannoma associated with esophageal cancer. A 70-year-old man visited our hospital complaining of worsening dysphagia. His upper gastrointenstinal endoscopy revealed a mass in the esophagus. A contrast-enhanced chest computed tomography also detected a 15 mm nodule attached to the tracheal membrane. This nodule was diagnosed as a metastatic lymph node. Although the primary tumor reduced after neoadjuvant chemotherapy, the nodule remained intact ; it showed fluorodeoxyglucose accumulation on positron emission tomography. We had a clinical diagnosis of stage III after neoadjuvant chemotherapy and underwent surgery. Intraoperatively, the nodule could not be detached from the right vagus nerve ; therefore, we excised the nodule along with the adjacent vagus nerve. The nodule was pathologically diagnosed as a vagus schwannoma. The nodule was not a regional lymph node metastasis of esophageal cancer. His postoperative course was uneventful, and he is currently undergoing outpatient follow-up without recurrence. J. Med. Invest. 68 : 205-208, February, 2021.

Endobronchial Ultrasound Improves the Diagnosis of the Tracheobronchial Invasion of Advanced Esophageal Cancer.

BACKGROUND: Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer. METHODS: We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes. RESULTS: Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis. CONCLUSION: CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication.

Biomarkers predicting the response to chemotherapy and the prognosis in patients with esophageal squamous cell carcinoma.

BACKGROUND: The prognosis of patients with esophageal squamous cell carcinoma (ESCC) has been improved by multidisciplinary therapy with chemoradiotherapy and surgery, but it remains poor. Advanced stage, malignant potential, and chemo-resistance contribute to the poor prognosis. Here, we attempted to identify predictive factors of the response to chemotherapy and the prognosis of ESCC patients. PATIENTS AND METHODS: We examined 51 ESCC patients who were treated with chemotherapy followed by radical surgery, and 23 patients who were treated with chemotherapy alone. We conducted quantitative reverse transcription-polymerase chain reaction gene expression analysis using RNA extracted from 74 tumor tissue samples collected before chemotherapy and 67 tumor tissue samples collected after chemotherapy, focusing on PIK3CA, AKT-1, mTOR, 4E-BP1, p70S6K, PD-L1, and PD-L2. RESULTS: The proportions of patients with high expressions of AKT-1 and PD-L1 before chemotherapy were significantly higher among the non-responders than among the responders (p = 0.034, p = 0.020, respectively). Multivariate analyses revealed that high PD-L1 expression before chemotherapy was associated with poor response to chemotherapy (odds ratio 2.998; 95% CI 1.043-8.619; p = 0.042) and high p70S6K expression before chemotherapy was a poor prognostic factor (hazard ratio 2.518; 95% CI 1.058-5.988; p = 0.037). In addition, the patients with high expression of PD-L1 and PD-L2 in the tumors after chemotherapy had significantly worse survival than those with low expression of these genes (p = 0.012, p = 0.007, respectively). CONCLUSION: These results demonstrated that PD-L1 and p70S6K in the primary ESCC tissues were related to a poor response to chemotherapy and poor prognosis, respectively.

Transcriptional Regulation of Müllerian Inhibiting Substance (MIS) and Establishment of a Gonadal Somatic Cell Line Using mis-GFP Transgenic Medaka (Oryzias latipes).

In vertebrate germ cell differentiation, gonadal somatic cells and germ cells are closely related. By analyzing this relationship, it has recently been reported in mammals that primordial germ cells (PGCs), induced from pluripotent stem cells and germline stem cells, can differentiate into functional gametes when co-cultured in vitro with fetal gonadal somatic cells. In some fish species, differentiation into functional sperm by reaggregation or co-culture of gonadal somatic cells and germ cells has also been reported; however, the relationship between gonadal somatic cells and germ cells in these species is not well-understood. Here, we report the transcriptional regulation of Müllerian inhibiting substance (MIS) and the establishment of a gonadal somatic cell line using mis-GFP transgenic fish, in medaka (Oryzias latipes)-a fish model which offers many advantages for molecular genetics. MIS is a glycoprotein belonging to the transforming growth factor ß superfamily. In medaka, mis mRNA is expressed in gonadal somatic cells of both sexes before sex differentiation, and MIS regulates the proliferation of germ cells during this period. Using luciferase assays, we found that steroidogenic factor 1 (SF1) and liver receptor homolog 1 (LRH1) activate medaka mis gene transcription, probably by binding to the mis promoter. We also report that mis-GFP transgenic medaka emit GFP fluorescence specific to gonadal somatic cells in the gonads. By fusing Sertoli cells from transgenic medaka with a cell line derived from medaka hepatoma cancer, we produced a hybridoma cell line that expresses gonadal somatic cell-specific markers, including Sertoli and Leydig cell markers. Moreover, embryonic PGCs co-cultured with the established hybridoma, as feeder cells, proliferated and formed significant colonies after 1 week. PGCs cultured for 3 weeks expressed a germ cell marker dnd, as well as the meiotic markers sycp1 and sycp3. Thus, we here provide the first evidence in teleosts that we have successfully established a gonadal somatic cell-derived hybridoma that can induce both the proliferation and meiosis of germ cells.

Safe central venous catheters for esophageal cancer treatment.

 Introduction : Central venous catheter (CVC) use is essential for treating esophageal cancer. Peripherally inserted central catheters (PICC) are commonly used recently for improved patient comfort and safety. We compared centrally inserted central catheters (CICC) and PICC insertions and examined their safety. Methods : We retrospectively investigated complications at the catheter insertion and post-insertion for 199 patients' esophageal cancer treatment (CICC : 45, PICC : 154) from 2013 to 2018. In addition, we summarized the results of catheter tip culture. Results : No serious complications occurred at the catheter insertion in either group. The rate of complications at catheter insertion was 5.8% for PICC and 6.7% for CICC patients. Post-insertion complications were observed in 6.5% and 11.1% of patients with PICC and CICC, respectively, and this difference was not significant. The incidence of catheter-related blood stream infection (CRBSI) was significantly lower in PICC than CICC patients (0.3 vs. 1.8 / 1,000 catheter-days ; p = 0.029). Catheter-related thrombosis was observed in PICC : 0.5 and CICC : 0.6, and occlusion due to blood flow reversal was observed in PICC : 0.5 and CICC : 0.6. Conclusion : PICCs are safer and more effective than CICCs for the treatment of esophageal cancer, and reduce the incidence of CRBSI. We hope to standardize the insertion procedures, conventionalize techniques, and establish training systems. J. Med. Invest. 67 : 298-303, August, 2020.

Towards cryogenic neutron crystallography on the reduced form of [NiFe]-hydrogenase.

A membrane-bound hydrogenase from Desulfovibrio vulgaris Miyazaki F is a metalloenzyme that contains a binuclear Ni-Fe complex in its active site and mainly catalyzes the oxidation of molecular hydrogen to generate a proton gradient in the bacterium. The active-site Ni-Fe complex of the aerobically purified enzyme shows its inactive oxidized form, which can be reactivated through reduction by hydrogen. Here, in order to understand how the oxidized form is reactivated by hydrogen and further to directly evaluate the bridging of a hydride ligand in the reduced form of the Ni-Fe complex, a neutron structure determination was undertaken on single crystals grown in a hydrogen atmosphere. Cryogenic crystallography is being introduced into the neutron diffraction research field as it enables the trapping of short-lived intermediates and the collection of diffraction data to higher resolution. To optimize the cooling of large crystals under anaerobic conditions, the effects on crystal quality were evaluated by X-rays using two typical methods, the use of a cold nitrogen-gas stream and plunge-cooling into liquid nitrogen, and the former was found to be more effective in cooling the crystals uniformly than the latter. Neutron diffraction data for the reactivated enzyme were collected at the Japan Photon Accelerator Research Complex under cryogenic conditions, where the crystal diffracted to a resolution of 2.0 Å. A neutron diffraction experiment on the reduced form was carried out at Oak Ridge National Laboratory under cryogenic conditions and showed diffraction peaks to a resolution of 2.4 Å.

Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration.

BACKGROUND: Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. METHODS: BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. RESULTS: Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. CONCLUSIONS: Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.

Non­invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small­animal FDG­PET/CT.

Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid carcinoma with a poor prognosis. Thus, suitable preclinical tumor models are required for the development of new ATC therapies. In the present study, orthotopic tumor xenograft models were established using ATC cell lines and SCID mice, and tumor invasion and the effects of anticancer drugs were evaluated using positron emission tomography/computed tomography (PET/CT) to repeatedly and non­invasively monitor these models. Three ATC cell lines (8305c, 8505c, and ACT­1) were used. Their sensitivities to two anticancer drugs (paclitaxel and lenvatinib) were investigated. The 8505c cell line was orthotopically implanted into SCID mice, which were then divided into three groups: No chemotherapy, paclitaxel (5 mg/kg, administered intraperitoneally, every week), and lenvatinib (5 mg/kg, oral route, every day) groups. PET/CT was performed and tumor growth and the effects of anticancer drugs based on tumor volume and fludeoxyglucose (FDG) uptake were evaluated. 8505c cells exhibited the highest sensitivity to the anticancer drugs. In mice implanted with 8505c cells, continuous increases in FDG uptake associated with tumor growth were detected on PET/CT in the group that received no chemotherapy. The tumor volume and FDG uptake increased by 91.5­ and 2.4­fold, respectively, within 2 weeks. The increase observed in tumor volume was 26.9­ and 12.2­fold in the paclitaxel and lenvatinib groups, respectively, within 2 weeks. Furthermore, the increase in FDG uptake was 1.8 and 1.6­fold in the paclitaxel and lenvatinib groups, respectively, within 2 weeks. In our orthotopic SCID mouse model, tumor growth and the effects of anticancer drugs were repeatedly and non­invasively monitored using PET/CT. The present method is useful for the development of new ATC treatments.

Metachromins X and Y from a marine sponge Spongia sp. and their effects on cell cycle progression.

New sesquiterpene quinones, metachromins X (1) and Y (2), together with the known metachromins C (3), J (4), and T (5), were isolated as inhibitors of cell cycle progression in the HeLa/Fucci2 cells. The structure of 1 was assigned by spectroscopic data and confirmed by a total synthesis. The planar structure of 2 was determined by interpretation of spectroscopic data, whereas its absolute configuration was analyzed by a combination of chiral HPLC and CD spectroscopy. Metachromins X (1) and C (3) arrested the cell cycle progression of HeLa/Fucci2 cells at S/G2/M phase.

The sterno-tracheal distance is an important factor of anastomotic leakage of retrosternal gastric tube reconstruction after esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009. METHODS: A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004-April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared. RESULTS: The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037). CONCLUSION: The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD < 13 mm.