The two therapeutic strategies of surgical intervention and medical management in a patient with enhanced-fibrinolytic type of disseminated intravascular coagulation after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure.

BACKGROUND: Management of the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by aortic disorders is the two strategies of surgical intervention and medical treatment based on the patient's age and comorbidities. CASE PRESENTATION: An 81-year-old woman with a history of two previous aortic surgeries and chronic heart and renal failure was admitted for uncontrollable subcutaneous hemorrhage. The hemorrhage was caused by the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by periprosthetic graft hematoma after aortic replacement for Stanford type A aortic dissection. Open thoracic hemostasis temporarily controlled the subcutaneous hemorrhage, but she was readmitted for the recurrence seven months after discharge. On the second admission, the combination of anticoagulant and antifibrinolytic agents was successful. CONCLUSION: Management of the enhanced-fibrinolytic type of DIC caused by aortic disorders is important of a successful combination of surgical and medical therapy tailored the patient's condition.

Discriminative Ability of Dynamic Chest Radiography to Identify Left Ventricular Dysfunction.

BACKGROUND: Dynamic chest radiography (DCR) produces sequential radiographs within a short examination time. It is also inexpensive and only uses a low dose of radiation. Because of the lack of reports of evaluating cardiac function using DCR in humans, we investigated its discriminative ability for left ventricular (LV) dysfunction in a study cohort.Methods and Results: We analyzed the DCR pixel values of 4 circular regions of interest (ROIs) in the hearts of 61 patients with cardiovascular disease and 10 healthy volunteers. We evaluated the relationship between changes in pixel value in the heart and the LV ejection fraction (LVEF) by echocardiography. We constructed receiver operating characteristic (ROC) curves to evaluate whether the percent change in pixel value (%∆pixel value) could be used to identify patients with reduced LVEF. A total of 21 patients had reduced LVEF (LVEF <50%), and 40 had preserved LVEF (LVEF ≥50%). The correlation between LVEF and %∆pixel value in each ROI was significant, and the area under the ROC curve of the %∆pixel values for identifying patients with reduced LVEF was satisfactory (0.808-0.827) in 3 ROIs where the entire circular area was within the cardiac shadow. CONCLUSIONS: LV dysfunction can be detected by changes in the pixel value on DCR.

Artesunate and cisplatin synergistically inhibit HNSCC cell growth and promote apoptosis with artesunate­induced decreases in Rb and phosphorylated Rb levels.

In the treatment of head and neck cancer, cisplatin is often used as a therapeutic agent; however, its efficacy is limited and it can cause renal dysfunction as an adverse effect. For this reason, the use of cisplatin is limited in elderly patients with reduced renal function. Recently, artemisinin, which was developed as an antimalarial drug, was found to have antitumor effects and is effective in combination with other anticancer drugs. In the present study, the antitumor effects of artemisinin and its derivatives as well as their combination with cisplatin and iron on head and neck squamous cell carcinoma cell lines, were investigated. Cell viability was determined by a cell viability assay, the cell cycle was analyzed by flow cytometry, cell death was assessed with annexin V and propidium iodide staining, and western blotting was used to analyze retinoblastoma protein (Rb), phosphorylated (p­)Rb, and other cell cycle­associated molecules. A total of four artemisinin compounds were examined and it was found that artesunate and dihydroartemisinin had a significant inhibitory effect on growth. It was also identified that the combination of artesunate, cisplatin, and iron inhibited cell proliferation and caused S/G2­M cell cycle arrest. In addition, western blotting of Rb, a molecule involved in the cell cycle, showed that artesunate induced the loss of not only Rb but also p­Rb. These results suggested that artesunate is a useful drug in combination with cisplatin.

Differences in clinical and echocardiographic features and outcomes between atrial functional mitral regurgitation patients with and without posterior mitral leaflet bending.

BACKGROUND: Posterior mitral leaflet (PML) bending is a cause of atrial functional mitral regurgitation (AFMR). We aimed to investigate differences in clinical and echocardiographic features and outcomes between AFMR patients with and without PML bending. METHODS: We retrospectively examined 118 AFMR patients with atrial fibrillation (AF), mild or greater MR without degenerative mitral valve changes, and left ventricular ejection fraction ≥50 %. Patients were classified by the presence of PML bending: PML bending (n=24) and no PML bending (n=94). PML bending was defined as PML-to-anterior mitral leaflet angle ratio ≥3.1 calculated using receiver operating characteristics analysis for eccentric MR jet toward left atrial posterior wall. The study endpoint was a composite of cardiac death, admission for heart failure, and mitral valve surgery. RESULTS: Overall, a total of 88 patients (75 %) had mild MR. There were no between-group differences in clinical and echocardiographic characteristics including AF duration and cardiac cavities size except for the length of inward bending of the left ventricular posterobasal wall and the mitral annular area. The 36-month event-free survival for the composite endpoint was significantly lower in the PML bending group (63 % vs. 78 %; Log-rank p=0.047). In multivariate analysis, PML bending was also associated with the composite outcome. CONCLUSIONS: AFMR patients with PML bending may have worse outcomes than those without PML bending despite similar clinical features.

A Novel Treatment Strategy for Advanced Lacrimal Sac Carcinomas Confirmed by p16 Immunostaining.

This article aims to describe the two cases in which chemotherapy and chemoradiotherapy were effective for advanced HPV-related lacrimal sac squamous cell carcinoma and avoided the need for radical surgery. This was an interventional study of two patients with advanced lacrimal sac squamous cell carcinoma. Two patients with advanced lacrimal sac squamous cell carcinoma were treated at our University Hospital between January 2020 and February 2021. Diagnosis of HPV-related lacrimal sac carcinoma was done by p16 immunostaining and RNA in situ hybridization. Received neoadjuvant chemotherapy and chemoradiotherapy, also minimally invasive surgery to remove any residual tumor if the final response, were unfavorable. HPV-related carcinoma was decided by checking p16 and RNA status. Response was assessed by computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, and endoscopic images. Both patients had positive p16 staining also HPV RNA in situ hybridization. Received definitive chemoradiotherapy instead of radical surgery after showing a partial response to neoadjuvant chemotherapy. A complete response was achieved in one patient and the other had a partial response, leaving a small residual tumor in the nose that was successfully removed by endonasal endoscopic surgery. Cure was achieved in two patients with HPV-related lacrimal sac squamous cell carcinoma by neoadjuvant chemotherapy followed by definitive chemoradiotherapy, with only one requiring minimally invasive surgery. This is a new direction in the treatment of p16-positive lacrimal sac carcinoma, especially for advanced cases, whereby molecular biological indicators can be used to avoid highly invasive surgery and preserve quality of life without compromising prognosis.

Successful Transcatheter Aortic Valve Implantation in a Patient with Radiation-induced Aortic Stenosis for Mediastinal Hodgkin Lymphoma.

Aortic stenosis (AS), a late complication of thoracic radiation therapy for chest lesions, is often coincident with porcelain aorta or hostile thorax. We herein report a 59-year-old man with a history of mediastinal Hodgkin lymphoma treated with radiation therapy but later presenting with heart failure caused by severe AS. Severe calcification in the mediastinum and around the ascending aorta made it difficult to perform surgical aortic valve replacement. The patient therefore underwent transcatheter aortic valve implantation (TAVI). It is important to recognize radiation-induced AS early, now that TAVI is a well-established treatment required by increasing numbers of successfully treated cancer patients.

Identification of cisplatin-resistant factor by integration of transcriptomic and proteomic data using head and neck carcinoma cell lines.

Cisplatin is an important drug for the treatment of head and neck squamous cell carcinoma (HNSCC). Determining chemoresistant factors prior to treatment will lead to great benefits for clinicians and patients. Here, we evaluated chemoresistant factors by integrating proteomic and transcriptomic data using HNSCC cell lines to identify a more precise chemoresistant factor in HNSCC. We used four HNSCC cell lines: cisplatin-sensitive, acquired cisplatin resistance, naturally cisplatin-resistant, and acquired 5-FU resistance. Proteomic analysis was performed using iTRAQ, tandem mass spectrometry, and liquid chromatography-electrospray ionization-tandem mass spectrometry. Transcriptomic analysis was performed using microarrays. By integrating these independent data, common factors were addressed and functional analysis was performed using small interfering RNAs (siRNAs) to change the chemosensitivity. Using iTRAQ analysis, 7 proteins were identified as specific for cisplatin chemoresistance factors. Transcriptomic analysis revealed hundreds of potential candidate factors. By combining and integrating these data, S100A2 was identified as a potential cisplatin-specific chemoresistance factor. Functional analysis with siRNA revealed that the expression of S100A2 was reduced and cisplatin sensitivity recovered in the acquired and naturally cisplatin-resistant cell lines, but not in the cisplatin-sensitive cell lines. S100A2 was identified as a cisplatin-specific chemoresistance factor by integrating the transcriptomic and proteomic results obtained using HNSCC cell lines. This is a novel technique that allows for a precise identification, also known as a comprehensive analysis. Our findings indicate that these proteins could be used as biomarkers of HNSCC treatments, providing physicians with new treatment strategies for patients with HNSCC, showing chemoresistance.

A novel Killian-Jamieson diverticulectomy using a thyroid gland flap: a case report.

BACKGROUND: A Killian-Jamieson diverticulum is a rare pharyngoesophageal diverticulum that is radically treated by diverticulectomy. However, there is no consensus on whether cricopharyngeal myotomy is necessary, and the optimal surgical methods that prevent postoperative complications such as leakage are undetermined. CASE PRESENTATION: A 49-year-old man was referred to our hospital with oropharyngeal dysphagia while eating. The patient was preoperatively diagnosed with a Killian-Jamieson diverticulum based on radiographic and clinical findings and underwent a transcervical diverticulectomy. The recurrent laryngeal nerves were preserved using an intraoperative nerve monitoring system, and the diverticulum was identified without difficulty. A partial cricopharyngeal myotomy was performed to expose the base of the diverticulum. The diverticulum was transected transversally using a linear stapler under the guidance of intraoperative upper intestinal endoscopy. A thyroid gland flap supplied by the superior thyroid artery was harvested and placed overlapping the area of the partial cricopharyngeal myotomy. Due to the proximity of the recurrent laryngeal nerve course to the diverticulum stump, the staple line was not buried with sutures. The thyroid gland flap with its rich vascular supply was fixed to completely cover the staple line on the cut surface of the thyroid gland. The postoperative course was uneventful, without vocal cord paralysis. The patient was discharged on postoperative day 8. He developed no clinical signs suggesting leakage, recurrence, or adverse events. CONCLUSION: Killian-Jamieson diverticulectomy using a thyroid gland flap and partial cricopharyngeal myotomy is a valid treatment option that may prevent complications and recurrence. Precise evaluation of the diverticulum using an intraoperative nerve monitoring system is crucial for the repair.

Pathological and Virological Studies of p16-Positive Oropharyngeal Carcinoma with a Good Response to Neoadjuvant Chemotherapy.

Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective.

Incisionless facial resection for Kadish stage C olfactory neuroblastoma: Transcaruncular approach with combined endonasal and skull base surgery.

This case report describes resection without facial incision for aggressive Kadish stage C olfactory neuroblastoma (ONB). We performed resection via transcaruncular approach with combined endonasal and skull base surgery. This multidisciplinary team surgical approach is expected to lead to a new strategy for this type of tumor in the future.

Distribution of descending necrotizing mediastinitis and efficacy of distribution-specific drainage.

BACKGROUND: Descending necrotizing mediastinitis (DNM) resulting from oropharyngeal and cervical abscess is a life-threatening condition. This study attempted to improve our recognition of the extension and distribution of the abscess for ideal thoracic drainage. METHODS: We performed a retrospective clinical analysis of seven patients who underwent thoracic drainage for DNM with available clinical data. For mapping and classification of the distribution of the abscess, computed tomography and intraoperative findings were utilized. RESULTS: To cure patients, cervical drainage and thoracic drainage were performed 14 and 11 times, respectively. The operation time for thoracic drainage and intraoperative blood loss were 141±77 min and 103±103 g, respectively. The mean hospital stay was 66±41 days. All patients are alive without recurrence. We divided the abscess distribution into nine categories including the anterior thoracic wall, according to the computed tomography and intraoperative findings. The rate of abscess descended gradually toward the lower mediastinum. Abscesses were not necessarily continuous, and skipped lesions were occasionally noted. CONCLUSIONS: We were able to cure all seven patients with DNM. It might be helpful to recognize the exact distribution of the abscess and distribution-specific drainage using a new map and classification of thoracic abscess.

Thyroid Gland Flap for Minimally Invasive Reconstructive Head and Neck Surgery.

Head and neck surgery sometimes causes small defects, and salvage surgery after chemoradiotherapy poses some risk because of damage to the surgical site from the previous treatment. We have developed a novel thyroid gland flap for head and neck surgical reconstruction and here we describe elevating the flap, including arc rotation, size, and suture technique, and our outcomes to date. METHODS: Thyroid gland flap reconstruction was performed in 13 cases (11 patients) between July 2009 and May 2020. The clinical importance and adverse effects of the procedure were examined. Thyroid function and blood flow of the flap were assessed, and the status of the flap and irradiated recipient tissue was examined histopathologically. RESULTS: Median age at surgery was 64.6 years (range 49-77 years). Two of the patients underwent reconstruction with a thyroid gland flap twice. There were 4 cases of primary head and neck cancer resection with neck dissection in which the flap was harvested from the thyroid gland as reinforcement. In 1 case, surgery was performed for cervical esophageal diverticulum. In all cases, the arc was limited to 6 cm and suturing was basic. There were no complications of the surgical procedure, and the postoperative course was uneventful. Contrast-enhanced computed tomography revealed adequate enhancement of the flap. Postoperative thyroid function was normal. The thyroid gland flap was firmly adapted and fused with the irradiated recipient tissue. CONCLUSION: The thyroid gland flap could be an effective tissue flap fed by the superior thyroid arteriovenous pedicle for head and neck reconstruction.

Thyroid gland flap minimizes mucosal defects at supracricoid partial laryngectomy with cricohyoidoepiglottopexy.

Wound infection is a major complication after supracricoid partial laryngectomy with cricohyoidoepiglottopexy (CHEP) for radiation therapy failure. A 60-year-old man received chemoradiotherapy for a glottic carcinoma. CHEP, reusing the thyroid gland flap (TF), was performed because the cancer recurred after a salvage vertical partial laryngectomy following radiation therapy failure. The TF was sutured to the supraglottis and cricoid cartilage mucosa to minimize mucosal defects before the hyoid bone and cricoid cartilage were sutured. Wound healing after CHEP was good without infection. After decannulation, oral food intake was possible without aspiration, and speech function was comparable to that of other patients who had supracricoid partial laryngectomies. Histopathological examination revealed a close connection between the TF and its surrounding tissues without fibrous scarring. TF may improve wound healing after CHEP for radiation failure by minimizing mucosal defects.

A novel larynx-preserving pharyngectomy technique using a thyroid gland flap after chemoradiotherapy.

This case report describes larynx-preserving pharyngectomy after chemoradiotherapy using a thyroid gland flap. A thyroid gland flap has good blood supply and reconstruction can be done in the same surgical field. The thyroid gland flap has potential as a novel appropriate flap for use in head and neck surgery.

Case of malignant transformation of vagus nerve schwannoma to angiosarcoma.

BACKGROUND: It is known that benign tumors have the potential for malignant transformation. Malignant transformation of vagus nerve schwannoma to angiosarcoma is very rare. METHODS: We report a case of malignant transformation in which the initial diagnosis was subsequently altered to angiosarcoma originating from the vagus nerve. We compared the findings of MRI and fine-needle aspiration (FNA) at initial diagnosis with those after malignant transformation. RESULTS: MRI revealed that the mass property had been changed from the initial tumor; also the FNA findings were significantly different from those in the previous ones. The patient had significant clinical progression with multiple cranial neuropathies and died. CONCLUSION: Schwannomas sometimes undergo malignant transformation; therefore, surgery should be recommended. If follow-up observation is chosen, MRI and FNA should be regular and patients should sign a statement acknowledging awareness of the potential for malignant transformation.

Case of partial vertical laryngectomy with vocal cord reconstruction using a thyroid gland flap.

BACKGROUND: To preserve laryngeal function in early-stage laryngeal cancer, chemotherapy and radiotherapy are performed more often than surgery as initial treatment. However, in recurrent cases, complex salvage surgery is often required as patients who received aggressive chemoradiotherapy are susceptible to postoperative complications. We report here salvage therapy that preserved laryngeal function in a recurrent case. METHODS: A 52-year-old man with recurrent laryngeal cancer (rT2N0M0) after chemoradiotherapy and followed by induction chemotherapy underwent partial vertical laryngectomy and right vocal cord reconstruction with a thyroid flap. RESULTS: Laryngeal functions were successfully preserved and the patient was discharged 2 months after surgery. CONCLUSION: The number of salvage surgeries performed after high-dose chemotherapy and radiation is expected to increase in the future. A thyroid gland flap promises to be an effective treatment option for vocal cord reconstruction especially for patients at high risk of postchemoradiotherapy complications.

Survival impact of pulmonary metastasectomy for patients with head and neck cancer.

BACKGROUND: The purpose of this study was to evaluate the survival impact and prognostic factors of pulmonary metastasectomy in patients with pulmonary metastasis from head and neck cancer. METHODS: A retrospective study of 69 patients was analyzed. Twenty-four patients (35%) underwent pulmonary metastasectomy, and the remaining 45 patients (65%) were treated with chemotherapy or best supportive care. RESULTS: The 1-year overall survival (OS) of 69 patients was 28%. Pulmonary metastasectomy (p = .01) and histology (p < .001) had a significant impact on the prognosis. One-year OS of patients who underwent metastasectomy and those who did not was 90% and 35%, respectively. In the metastasectomy group, recurrence of primary ahead of lung metastasis (p = .006) and disease-free interval (DFI; ≤21.4 months; p = .046) were significant negative prognostic factors. CONCLUSION: Pulmonary metastasectomy has an impact on survival in carefully selected patients, especially for those with a long DFI and with no recurrence of primary cancer ahead of lung metastasis.

In vitro study on the transport of zinc across intestinal epithelial cells using Caco-2 monolayers and isolated rat intestinal membranes.

The variety of physiologic and biologic functions of zinc is fascinating and could be applicable to medicine. Our previous studies demonstrated that the absorption of zinc after oral administration to rats is dose-dependent. In order to clarify the detailed mechanism of the dose-dependent in vivo absorption, the transport of zinc across intestinal epithelial cells was investigated using Caco-2 monolayers and isolated rat intestinal membranes. The permeation of zinc across Caco-2 monolayers is concentration-dependent, and both saturable and nonsaturable components are involved. The Michaelis constant and maximum transport rate for saturable transport are 11.7 µM and 31.8 pmol min(-1) cm(-2), respectively; the permeability coefficient for nonsaturable trasnport is 2.37×10(-6) cm s(-1). These parameters for permeation across membranes isolated from duodenum, ileum, and jejunum of rats are similar with those of Caco-2 cells. The comparison of the parameters for permeation across isolated intestinal membrane suggests that the major site of intestinal zinc absorption in rats is the duodenum. The maximum rate of zinc transport across the isolated intestinal membrane (V(max)) shows no correlation with mRNA expression of ZIP4, ZIP5 or ZnT1 in rats, but shows an inverse correlation with that of metallothioneins (MTs). This finding may be partly explained by the buffering role of metallothionein in intestinal absorption. The saturable transport of zinc is not simply determined only by the influx transporter, ZIP4, since three influx and efflux transporters are involved in the transport of zinc.

The disposition and intestinal absorption of zinc in rats.

The variety of physiologic and biologic functions of zinc is expected to enable the development of zinc-related medicines. In this study, the distribution of endogenous zinc, the disposition after intravenous injection, and the intestinal absorption of zinc were investigated in vivo using rats from the viewpoints of pharmaceutical science and pharmacokinetics. High levels of endogenous zinc were observed in bone, testis, and liver. RT-PCR analysis on the mRNA of metallothionein in tissues clarified that it is significantly correlated with the distribution of zinc, suggesting that zinc is accumulated in tissues as a complex with MT. Following intravenous injection, uptake of zinc was high in liver, spleen, pancreas, kidney, and intestine. Fractional absorptions of zinc after oral administration to fasted rats were greater than those to fed rats, suggesting that some factors in diet inhibit the absorption of zinc. In fasted rats, fractional absorption was slightly decreased in high-dose group, suggesting the involvement of carrier-mediated transport. Study utilizing an in situ closed-loop method also indicated saturable intestinal absorption of zinc. These findings will further the research and development of zinc-related medicines by providing basic and important information on zinc.