A Stepwise Progression of Acute Bilateral Visual Loss Due to Onodi Cell Sinusitis.

Acute visual loss in an immunocompromised patient may be caused by acute invasive fungal sinusitis (AIFS), even if symptoms include only mild headache and computed tomography (CT) shows only mild sinusitis, especially of the Onodi cell. Herein, we report a case of a 71-year-old man with a medical history of dermatomyositis and type 2 diabetes mellitus who presented with a stepwise progression of acute bilateral visual loss, mild headache, and altered consciousness. Initially, as the plain cranial CT showed only mild fluid retention in the posterior ethmoid sinus without bone destruction, the sinusitis was considered unrelated to the visual loss. Afterward, however, contrast-enhanced cranial magnetic resonance imaging (MRI) showed mucosal thickening, fluid retention in the posterior ethmoid sinus, and spread of the contrast medium over the dura around the right posterior ethmoid sinus and bilateral optic nerve tracts. Aspergillus fumigatus was identified from endoscopic drainage of the sinus. The patient was diagnosed with AIFS and treated with amphotericin B 350 mg/day. The altered sensorium and headache rapidly improved, and his left visual acuity improved to counting fingers. Although AIFS is rare, it can cause severe sequela or death due to vascular or direct intracranial invasion. Therefore, immediate drainage of the sinus and intravenous antifungal therapy are essential for AIFS. Our findings will help physicians make accurate and rapid diagnoses of AIFS in future cases.

Preoperative simulation using three-dimensional printer in four temporal bone surgeries.

Preoperative simulation using a three-dimensional printer is effective to perform safe surgery by knowing the range limit of drilling in the temporal bone. Moreover, simulations using models are thought to be useful for education of young surgeon.

Noteworthy Factors to Decide Therapeutic Strategy for Carcinoma ex Pleomorphic Adenoma of Parotid Gland: A Preliminary Study Statistical Analysis of 22 Cases from Single Institution.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor, and its prognosis is determined by the histological progression beyond the adenoma capsule. However, a preoperative evaluation of the histological progression remains challenging, and there is no consensus regarding treatment strategies for CXPA. Herein, we aimed to predict the histological progression preoperatively and develop an appropriate treatment strategy for CXPA. We retrospectively reviewed 22 patients with parotid gland CXPA recorded at our hospital. The clinicopathological characteristics were assessed, and survival analysis was performed. T3≤ or N+ were common in widely invasive CXPA (WICXPA) (p < 0.05). A tumor diameter > 40 mm and the N+ status were associated with poor prognosis considering overall survival (OS) and locoregional recurrence rate (LRC) (p < 0.05). Patients with facial nerve paralysis exhibited better OS and LRC than those without facial nerve paralysis. More than 90% of patients with WICXPA experienced distant metastases. Meanwhile, there were no cases of recurrence or death due to intracapsular and minimally invasive CXPA. A preoperative advanced T stage or N+ status was suspected as WICXPA. Tumors > 40 mm in size and N+ status necessitate high-intensity local treatment. Facial nerve invasion can be controlled by nerve resection. Postoperative systemic therapy could control distant metastases.

A case of jugular bulb diverticulum causing pulsatile tinnitus.

If you suspect pulsatile tinnitus from a medical interview, you should check for jugular bulb diverticulum and cortical bone defects on temporal bone CT, in addition to thorough physical examination and contrast-enhanced imaging.

Clinical characteristics of patients with pneumatosis intestinalis.

BACKGROUND: Several theories explaining the development of pneumatosis intestinalis (PI) have been reported, but a substantial portion of cases have been idiopathic. Additionally, predictors of bowel ischaemia in PI have not been fully investigated, while PI with bowel ischaemia has deteriorated overall outcomes of PI. METHODS: Sixty-four patients diagnosed with PI (2009-2019) were allocated to two groups: with (group 1; n = 15 (23%)) and without (group 2; n = 49 (77%)) bowel ischaemia. Fourteen patients underwent emergency surgery, and bowel ischaemia was identified in nine (64%). Six patients in group 1 were diagnosed with bowel ischaemia, and were treated palliatively. On medical charts, we determined underlying conditions of PI, compared the characteristics and outcomes between the groups, and identified the predictors of bowel ischaemia. RESULTS: Group 1 patients more commonly showed abdominal pain, lower base excess, higher C-reactive protein concentrations, higher white blood cell counts and higher neutrophil-to-lymphocyte ratios, and more frequent comorbid ascites, free air and hepatic portal vein gas. Of nine bowel ischaemia surgery patients, three (33%) died; all because of anastomotic leak. All except three patients in group 2, who presented with aspiration pneumonia, responded to treatment. Only one patient had an unknown cause (1/64, 1.6%), and various underlying conditions in secondary PI were confirmed. CONCLUSION: Idiopathic PI may be identified rarely using current imaging and knowledge, but outcomes in PI patients with bowel ischaemia remain unsatisfactory. Earlier identification of bowel ischaemia by various specialists in accordance with predictors of bowel ischaemia could improve overall outcomes in PI patients.

Clinical features of patients with hepatic portal venous gas.

BACKGROUND: Hepatic portal venous gas (HPVG) is a rare clinical condition that is caused by a variety of underlying diseases. However, the factors that would permit accurate identification of bowel ischemia, requiring surgery, in patients with HPVG have not been fully investigated. METHODS: Thirty patients that had been diagnosed with HPVG using computed tomography between 2010 and 2019 were allocated to two groups on the basis of clinical and intraoperative findings: those with (Group 1; n = 12 [40%]) and without (Group 2; n = 18 [60%]) bowel ischemia. Eleven patients underwent emergency surgery, and bowel ischemia was identified in eight of these (73%). Four patients in Group 1 were diagnosed with bowel ischemia, but treated palliatively because of their general condition. We compared the characteristics and outcomes of Groups 1 and 2 and identified possible prognostic factors for bowel ischemia. RESULTS: At admission, patients in Group 1 more commonly showed the peritoneal irritation sign, had lower base excess, higher lactate, and higher C-reactive protein, and more frequently had comorbid intestinal pneumatosis. Of the eight bowel ischemia surgery patients, four (50%) died, mainly because of anastomotic leak following bowel resection and primary anastomosis (3/4, 75%). All except one patient in Group 2, who presented with aspiration pneumonia, responded better to treatment. CONCLUSIONS: Earlier identification and grading of bowel ischemia according to the findings at admission should benefit patients with HPVG by reducing the incidence of unnecessary surgery and increasing the use of safer procedures, such as prophylactic stoma placement.

Splenic artery aneurysm rupture during pregnancy: A case report of maternal and fetal survival.

INTRODUCTION: Pregnancy has been demonstrated as a significant risk factor of splenic artery aneurysm (SAA) formation and rupture. However, prompt diagnosis of SAA rupture in a pregnant patient showing acute abdomen has been practically challenging in light of its rarity and vague initial presentation. PRESENTATION OF CASE: A 40-year-old woman (gravida 1, para 0) at 35 weeks' gestation presented to the emergency department with upper abdominal pain and nausea. Because of fetal dysfunction, emergency caesarian section was performed by a Pfannenstiel incision. Following delivery, 400 g of hemorrhage was removed from the upper abdominal cavity. Computed tomography showed a 37-mm SAA associated with copious adjacent fluid. Although selective angiography did not demonstrate active extravasation, interventional isolation of the SAA was not performed because of multiple surrounding arteries. Relaparotomy with an upper midline incision was then performed. Sudden cardiac arrest occurred upon opening the lesser sac to irrigate clots, and cardiac massage and proximal and distal clamping of the SAA were required. Eventually, splenectomy with excision of the SAA and pancreatic tail was successfully performed, but gauze packing of the open surgical wound was required because of severe coagulopathy. Following removal of the packs and closure of the abdomen 2 days after splenectomy, the patient and infant satisfactorily recovered without sequelae. DISCUSSION: Given continual awareness of abdominal vascular collapse during pregnancy, undelayed diagnosis and safer intervention might be achieved. CONCLUSION: Awareness at initial presentation and multidisciplinary efforts might be essential to achieve maternal and fetal survival in SAA rupture during pregnancy.

Regulatory T cells induce CD4- NKT cell anergy and suppress NKT cell cytotoxic function.

BACKGROUND: Due to the strong tumoricidal activities of activated natural killer T (NKT) cells, invariant NKT cell-based immunotherapy has shown promising clinical efficacy. However, suppressive factors, such as regulatory T cells (Tregs), may be obstacles in the use of NKT cell-based cancer immunotherapy for advanced cancer patients. Here, we investigated the suppressive effects of Tregs on NKT cells and the underlying mechanisms with the aim to improve the antitumor activities of NKT cells. METHODS: Peripheral blood samples were obtained from healthy donors, patients with benign tumors, and patients with head and neck squamous cell carcinoma (HNSCC). NKT cells, induced with α-galactosylceramide (α-GalCer), and monocyte-derived dendritic cells (DCs) were co-cultured with naïve CD4+ T cell-derived Tregs to investigate the mechanism of the Treg suppressive effect on NKT cell cytotoxic function. The functions and phenotypes of NKT cells were evaluated with flow cytometry and cytometric bead array. RESULTS: Treg suppression on NKT cell function required cell-to-cell contact and was mediated via impaired DC maturation. NKT cells cultured under Treg-enriched conditions showed a decrease in CD4- NKT cell frequency, which exert strong tumoricidal responsiveness upon α-GalCer stimulation. The same results were observed in HNSCC patients with significantly increased effector Tregs. CONCLUSION: Tregs exert suppressive effects on NKT cell tumoricidal function by inducing more CD4- NKT cell anergy and less CD4+ NKT cell anergy. Both Treg depletion and NKT cell recovery from the anergy state may be important for improving the clinical efficacy of NKT cell-based immunotherapy in patients with advanced cancers.

Total Nasal Reconstruction with a Nonlaminated Vascularized Free Temporal Fascia as the Lining.

Various methods to generate the lining for a full-thickness nasal reconstruction have been reported. We used bilateral septal mucoperichondrial flaps, the distal portion of an expanded median forehead flap, and a nonlaminated vascularized free temporal fascia flap as a lining during total nasal reconstruction of a total full-thickness nasal defect in a 45-year-old woman with a nasal squamous cell carcinoma. In the first step of the two-stage surgery, a tissue expander was inserted into the forehead simultaneously with tumor resection. In the second step, the expanded median forehead flap, cartilage graft, bilateral septal mucoperichondrial flaps, and short pedicle vascularized free temporal fascia transfer were performed. Total nasal reconstruction could be completed without any skin graft or skin paddle of the free flap. Epithelialization of the mucosa on the transferred vascularized free temporal fascia without contracture deformity of the nasal cavity was confirmed by endoscopic examination after 8 years of follow-up. In the surgical procedure described, the facial skin, including the lining of the nostril rim, and the mucous membrane of the nasal cavity were reconstructed using facial skin and mucous membrane without long-term contracture, respectively.

Perioperative management of laparoscopic surgery in a patient with protein S deficiency complications: A case report.

Patients with protein S deficiency are prone to developing thrombosis. During laparoscopic surgery in patients with protein S deficiency, there is a risk of deep venous thromboembolism. In the present case, the patient was a 66-year-old man. He was diagnosed with colon cancer, and surgery was planned. Because of the presence of protein S deficiency, he required careful perioperative management for laparoscopic surgery. Surgery was successfully performed. On postoperative assessment, no thrombi were observed. Our approach of perioperative management might help in the treatment of patients with protein S deficiency.

Endoscopic contralateral transmaxillary approach for pterygoid process osteotomy in total maxillectomy: A technical case report.

An approach for total maxillectomy with endoscopic transection of the pterygoid process via the contralateral maxillary sinus is described. In total maxillectomy, the resection of the pterygoid process of the sphenoid is a key step for successful resection. However, a conventional craniofacial approach requires extensive incision in the face, elevation of the lateral cheek flap. Even after elevation of the lateral cheek flap, visualization of this region is not good. An endoscopic approach through the contralateral maxillary sinus improved visualization of the pterygoid process, and osteotomy using a diamond-drilling bar was successfully performed. This technique has the potential to widen the indication for total maxillectomy in malignant neoplasms of the maxillary sinus.

CD45RA-Foxp3high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma.

BACKGROUND: Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3. METHOD: The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined. RESULTS: The frequency of CD4+Foxp3+ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RA-Foxp3high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RA-Foxp3high Tregs correlated with a poor prognosis and the low frequency of CD45RA-Foxp3high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RA-Foxp3high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation. CONCLUSION: CD45RA-Foxp3high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.

Adamantinoma-like Ewing family tumor of soft tissue associated with the vagus nerve: a case report and review of the literature.

Adamantinoma-like Ewing family tumor (EFT) is a rare subset of EFTs showing mixed features of Ewing sarcoma and adamantinoma of the long bones. All currently reported cases of the adamantinoma-like type have been associated with bone. Recently, a unique type of EFT was reported showing complex epithelial differentiation associated with the vagus nerve. Here we describe another unique type of EFT arising in the soft tissue of the neck associated with the vagus nerve. An 11-year-old girl presented to our hospital with a neck tumor on her right side. Surgical resection was performed, and histopathologic examination demonstrated a high-grade malignant neoplasm. The tumor was composed of sheets of small round proliferating cells, basaloid tumor nests with marked squamous differentiation, biphasic growth pattern with epithelioid tumor nests, and spindle cell proliferation. Immunohistochemically, the tumor cells showed diffuse expression of CD99 and FLI-1. In addition, small round cells and basaloid/squamoid components were immunoreactive for AE1/AE3, CAM5.2, cytokeratin 5/6, high-molecular weight keratin, p63, and p40 (ΔNp63). Reverse transcription polymerase chain reaction and direct sequencing analysis revealed that the tumor harbored a t(11;22) translocation, involving EWSR1 and FLI-1, which are characteristic of EFTs. According to these findings, our case has characteristics of both a subset of adamantinoma-like EFT and EFT with complex epithelial differentiation. We suggest that EFT with complex epithelial differentiation is in a common spectrum with the adamantinoma-like type and that adamantinoma-like EFTs can arise in soft tissue, leading to difficulty in differential diagnosis with malignant epithelial tumors.

Development of a heme sensor using fluorescently labeled heme oxygenase-1.

Free heme, the protein-unbound form of heme, has both toxic and regulatory effects on cells. To detect free heme at low concentrations, we developed a heme sensor using fluorescently labeled heme oxygenase-1 (HO-1), an enzyme that catalyzes oxidative heme degradation and has a high affinity for heme. The response of the heme sensor is based on the fluorescence quenching that occurs when heme binds to the enzyme. Each of the three fluorescently labeled HO-1s exhibits a 1:1 binding stoichiometry and an absorption spectrum similar to that of the heme complex of the wild-type HO-1. Titration of the labeled proteins with hemin resulted in fluorescence quenching in a hemin concentration-dependent manner, presumably due to an energy transfer from the fluorophore to the heme bound to HO-1. The sensor showed a potent affinity for heme with a dissociation constant in the low nanomolar range and a high selectivity for heme. Based on the linear response of the sensor to heme, we performed a fluorometric microplate assay. The sensor was able to selectively detect free heme but did not respond to heme bound to native hemoglobin. This assay will be a useful tool for determination of free heme in biological samples containing protein-bound heme.

Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-galactosylceramide-pulsed antigen presenting cells.

PURPOSE: The intravenous administration of α-Galactosylceramide (α-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-γ producing cells in the peripheral blood after the treatment appeared to be associated with prolonged survival. An exploratory study protocol was designed with the preoperative administration of α-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site. METHODS: Patients with operable advanced lung cancer received an intravenous injection of α-GalCer-pulsed APCs before surgery. The resected lung and tumor infiltrating lymphocytes (TILs) as well as peripheral blood mononuclear cells were collected and the invariant NKT (iNKT) cell-specific immune responses were analyzed. RESULTS: Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-γ production by the α-GalCer-stimulated TILs. CONCLUSION: The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.

Nasal submucosal administration of antigen-presenting cells induces effective immunological responses in cancer immunotherapy.

Human NKT cells are known to have strong antitumor activities and to be activated by specific ligand, α-galactosylceramide (αGelCer). We examined the migration pattern of αGalCer-pulsed DCs and the immune responses after administration by different routes. DCs injected into nasal submucosa quickly migrated to the lateral neck lymph rather than the lateral lymph nodes. The absolute number of NKT cells and the IFN-γ-producing cells increased in peripheral blood after injection of the DCs into nasal submucosa. We conducted a phase I study with αGalCer-pulsed DCs administered in nasal submucosa of patients with head and neck cancer, and evaluated safety and feasibility. The results showed that nasal submucosal administration of α-GalCer-pulsed DCs was safe and a smaller number of these DCs could exhibit significant immune responses and some positive clinical effects. In additional study, the use of the intra-arterial infusion of activated NKT cells and the submucosal injection of α-GalCer-pulsed DCs has been shown to induce significant antitumor immunity and had beneficial clinical effects in the management of advanced head and neck squamous cell carcinoma. The NKT cell-based cancer immunotherapy may be helpful in management of head and neck cancer and needs to be explored in further detail.

A randomized, double-blind, placebo-controlled study of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis.

OBJECTIVE: Self-care with ten-cha is the most common complementary alternative medicine for allergic rhinitis in Japan, but evidence for an actual therapeutic effect is lacking. The purpose of the study was to investigate the effect of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis. METHODS: The study was performed in the otolaryngology departments of 5 facilities (Chiba University, Kagoshima University, Fukui University, Okayama University, and Nippon Medical School) from July to December 2009. A randomized double-blind study was performed with central enrollment and allocation. The subjects ingested 400mg of ten-cha extract or placebo (3 capsules/day) daily for 4 weeks as a food intervention. The number of subjects was chosen with anticipation of an effect equivalent to that of mast cell-stabilizing drugs. A nasal allergy diary-based symptom score and a QOL score were used for evaluation. RESULTS: The ten-cha and placebo groups included 47 and 42 subjects, respectively. The improvement rates for sneeze, nasal discharge, nasal obstruction, and symptom scores were greater in the ten-cha group than in the placebo group throughout the intervention period, and the effect tended to increase with time in the ten-cha group. However, the differences between the groups were not significant. QOL was not significantly improved in either group. CONCLUSION: Ingestion of ten-cha had an effect on allergic rhinitis, but the effect of Ten-Cha was limited and did not differ significantly from placebo. These results suggest that ten-cha does not exhibit an effect equivalent to mast cell-stabilizing drugs at the dose used in this study.

Migration and immunological reaction after the administration of αGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer.

BACKGROUND: Antigen-presenting cells (APCs) play a crucial role in the induction of immune responses. However, the optimal administration route of tumor-specific APCs for inducing effective immunological responses via cancer immunotherapy remains to be elucidated. Human NKT cells are known to have strong anti-tumor activities and are activated by the specific ligand, namely, α-galactosylceramide (αGalCer). METHODS: Seventeen patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in this study. Patients received an injection of αGalCer-pulsed APCs into the nasal, or the oral floor submucosa. Then total body image and single photon emission computed tomography (SPECT) images were examined. The immunological responses including the number of peripheral blood NKT cells, anti-tumor activities and the CD4(+) CD25(high) Foxp3(+) T cells (Tregs) induced following APCs were also compared. RESULTS: APCs injected into the nasal submucosa quickly migrated to the lateral lymph nodes and those injected into the oral floor submucosa dominantly migrated to the submandibular nodes rather than the lateral lymph nodes. An increase in the absolute number of NKT cells and the IFN-γ producing cells was observed in peripheral blood after injection of the APCs into the nasal submucosa, however, these anti-tumor activities were not detected and the increased frequency of Treg cells were observed after administration into oral floor. CONCLUSIONS: These results indicate that a different administration route of APCs has the potential to bring a different immunological reaction. The submucosal administration of αGalCer into the oral submucosa tends to induce immunological suppression.

Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy.

Vα24 natural killer T (NKT) cells have potent anti-tumor activity. We performed a phase II clinical study in patients with head and neck squamous cell carcinoma (HNSCC) using ex vivo expanded Vα24 NKT cells and α-galactosylceramide (αGalCer; KRN7000)-pulsed antigen-presenting cells (APCs) to investigate the efficacy and induction of NKT cell-specific immune responses. The subjects were 10 patients with locally recurrent and operable HNSCC. One course of nasal submucosal administration of αGalCer-pulsed APCs and intra-arterial infusion of activated NKT cells via tumor-feeding arteries was given before salvage surgery. Anti-tumor effects, NKT cell-specific immune responses in extirpated cancer tissue and peripheral blood, safety, and pathological effects were evaluated. Five cases achieved objective tumor regression. The number of NKT cells increased in cancer tissues in 7 cases and was associated with tumor regression. The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects.

A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy.

Invariant natural killer T (iNKT) cells possess potent antitumor effects after activation with a specific glycolipid antigen, α-galactosylceramide (αGalCer). A phase I-II clinical study of αGalCer-pulsed dendritic cells (DC) to activate endogenous iNKT cells was previously performed in patients with non-small-cell lung cancer (NSCLC). In this clinical trial, the patients with increased interferon-γ (IFN-γ) production (>two-fold) in PBMC after the DC treatment (good responder group) experienced a prolonged overall survival time in comparison with the poor responder group. We extended the previous study and performed a microarray-based gene expression analysis using peripheral blood CD56(+) cells and CD56(-) CD3(+) T cells from patients enrolled in the above-mentioned clinical study. We sought to identify any biomarkers associated with the immune responses in this immunotherapy trial. Six patient samples corresponding to three subjects in the good responder group and three subjects in the poor responder group were included in the microarray analysis. Genes differentially expressed between pre-treatment and post-treatment samples were selected for analysis. Subsequently, genes that were only expressed in the good responder group or poor responder group were chosen. After these procedures, four selected genes were quantified by reverse transcriptase-polymerase chain reaction in another eight patient samples, and two genes, LTB4DH and DPYSL3, were confirmed to be candidate genes for the predictor of a good immune response. The expression profile of these two genes may be associated with the responsiveness of IFN-γ production after αGalCer-pulsed DC treatment.