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Temporomandibular joint herniation (TJH) is a rare condition in which the contents of the temporomandibular joint herniate into the external auditory canal (EAC). The foramen of Huschke (FH), also known as the foramen tympanicum, is an anatomical defect in the anteroinferior aspect of the EAC bone, and persisting FH is thought to be one of the causes of TJH. We report a case of spontaneous TJH along with a review of the literature. A 42-year-old man with aural fullness visited our department for the examination of the temporomandibular joint and a potentially neoplastic lesion in March 2020. Computed tomography performed previously showed a soft tissue density with a bone defect in the anterior wall of the left EAC. Otoscopic examination revealed a dome-shaped raised mass in the anterosuperior wall of the left side of the EAC. The mass protruded when the mouth was closed and disappeared when the mouth was opened. The patient was diagnosed with left TJH based on the clinical and imaging findings. Due to the lack of clinical symptoms, we decided not to perform aggressive surgical treatment for TJH, but to follow up carefully with regular imaging examinations. Fifteen months have passed since the first visit, and the symptoms have not worsened. This case report shows that TJH presents with characteristic clinical and imaging findings. Therefore, understanding the pathophysiology of this disease is essential for oral and maxillofacial surgeons who deal with temporomandibular joint diseases on a daily basis.

A mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary gland. It frequently occurs in the parotid and minor salivary glands, but rarely originates from the sublingual gland. We report a case of a low-grade MEC arising from the sublingual gland with a MAML2 gene split on fluorescence in situ hybridization (FISH). In May 2017, a 57-year-old woman visited our hospital with left-sided tongue numbness and swelling of the floor of the mouth. We performed a biopsy, but the lesion was indistinguishable from malignant tumors such as MEC, or atypical epithelium associated with inflammation. Subsequently, an MEC was suspected based on computed tomography findings of invasion into the bone marrow and destruction of the outer margin of the mandibular cortex. In July 2017, tracheostomy, bilateral supraomohyoid neck dissection, combined resection of the floor of the mouth and reconstruction of the free peroneal composite flap with a vascular handle were performed under general anesthesia. Although perineural and mandibular invasion was observed, the tumor was considered a low-grade malignancy based on histopathological findings. Furthermore, a split signal in the MAML2 gene was detected on detailed molecular analysis using FISH. No recurrence was observed more than three years after definitive surgery. The presence of the MAML2 fusion gene is useful for the accurate diagnosis of an MEC. Overall, we report a rare case of an MEC in the sublingual gland with mandibular invasion where MAML2 fusion was confirmed.

COVID-19 is pandemic since 2020 and further information is necessary on the risk factors associated with the infection of SARS-CoV-2. As an entry mechanism, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as receptor and transmembrane serine protease 2 (TMPRSS2) to activate fusion with host plasma membrane. Because dysgeusia is an early symptom of COVID-19, we here studied the expression of ACE2 and TMPRSS2 in the tongue and the associated tissues of mice and humans with immunohistochemistry and immunoblot analysis. ACE2 expression was low in the human tongue but was observed in the squamous epithelium, perineurium, arterial wall, salivary glands as well as taste buds. In contrast, mice showed high expression. In sharp contrast, TMPRSS2 expression was high in all the cells mentioned above in humans but relatively low in mice except for salivary glands. We then performed semi-quantitation of immunohistochemistry data of human ACE2 and TMPRSS2 and analyzed for age, sex, alcohol intake, and smoking habit with logistic regression analysis. We found that alcohol intake and female gender were the significant risk factors for increasing TMPRSS2 expression. In conclusion, TMPRSS2 is an important factor to be considered regarding SARS-CoV-2 entry and amplification in the oral cavity, which is promoted through drinking habit.

Lingual artery (LA) aneurysms are particularly rare, and pseudoaneurysms are associated with trauma, infection, and surgical intervention. LA aneurysms can be fatal if not recognised or treated; however, only a few cases of idiopathic LA aneurysms have been reported in the literature, all of which have been described as pseudoaneurysms. To address this knowledge gap in reporting a true LA aneurysm, here, we describe a 55-year-old woman with an idiopathic aneurysm of the lingual artery. The lesion was detected by another department on a computed tomographic angiography of the neck, which was performed as a post-aneurysmectomy evaluation of the right internal carotid artery. The embolisation failed twice, after which we performed an aneurysmectomy of the left atrium. A histopathological examination of the excised aneurysms revealed fibromuscular dysplasia (FMD). Thus, we believe that FMD may be a cause of external LA aneurysms. Our findings will be relevant for oral surgeons and physicians who may consider FMD as a differential diagnosis when treating multiple LA aneurysms.

Ossifying fibroma is a fibro-osseous lesion of the jaw and usually occurs as a single lesion. Little is known about ossifying fibromas, which occur as a manifestation of hyperparathyroidism-jaw tumor syndrome (HPT-JT), an autosomal dominant disorder. We experienced a patient with HPT-JT who had ossifying fibromas on both sides of the mandible. A 32-year-old female was referred to our department because of swelling on the right side of the mandible. She had a history of parathyroid adenomas and endometrial hyperplasia; however, there was no family history of parathyroid, mandibular, or renal lesions. She was diagnosed with recurrent parathyroid adenoma close to the time of her visit to our department. A biopsy revealed that the jaw lesion was an ossifying fibroma, and genetic testing revealed HPT-JT. She underwent surgery for the parathyroid and mandibular lesions and is currently undergoing follow-up. Accurate diagnosis of HPT-JT is important because it is an inherited condition and is associated with a high incidence of parathyroid carcinoma. This case indicates that cooperation among multiple medical care departments is essential for proper diagnosis and treatment of HPT-JT.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. HNSCC patient prognosis is closely related to the occurrence of tumor metastases, and collagen within the tumor microenvironment (TME) plays a key role in this process. Lysyl hydroxylase 2 (LH2), encoded by the Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2 (PLOD2) gene, catalyzes hydroxylation of telopeptidyl lysine (Lys) residues of fibrillar collagens which then undergo subsequent modifications to form stable intermolecular cross-links that change the biomechanical properties (i.e. quality) of the TME. While LH2-catalyzed collagen modification has been implicated in driving tumor progression and metastasis in diverse cancers, little is known about its role in HNSCC progression. Thus, using gain- and loss-of-function studies, we examined the effects of LH2 expression levels on collagen cross-linking and cell behavior in vitro and in vivo using a tractable bioluminescent imaging-based orthotopic xenograft model. We found that LH2 overexpression dramatically increases HNSCC cell migratory and invasive abilities in vitro and that LH2-driven changes in collagen cross-linking robustly induces metastasis in vivo. Specifically, the amount of LH2-mediated collagen cross-links increased significantly with PLOD2 overexpression, without affecting the total quantity of collagen cross-links. Conversely, LH2 knockdown significantly blunted HNSCC cells invasive capacity in vitro and metastatic potential in vivo. Thus, regardless of the total “quantity” of collagen crosslinks, it is the “quality” of these cross-links that is the key driver of HNSCC tumor metastatic dissemination. These data implicate LH2 as a key regulator of HNSCC tumor invasion and metastasis by modulating collagen cross-link quality and suggest that therapeutic strategies targeting LH2-mediated collagen cross-linking in the TME may be effective in controlling tumor progression and improving disease outcomes.

Jaw-closing oromandibular dystonia (JCOD) is a potential symptom of dystonia. Because aspects of its pathogenesis and effective treatment remain to be determined, treating JCOD is challenging. There are some reports that JCOD may lead to secondary tooth wear and temporomandibular joint dysfunction, but whether associated severe bruxism can cause maxillary sinusitis after a bite injury is unknown. Herein we report a case of maxillary inflammation involving maxillary sinusitis after JCOD associated with hypoxic encephalopathy. A 60-year-old woman with JCOD as a symptom of generalized dystonia was referred to our department due to gingival swelling and bleeding in the region of the bilateral maxillary molars. The gingiva of the bilateral maxillary molars had evidently been injured by the mandibular molars. Computed tomography revealed dense soft-tissue masses in the bilateral maxillary sinuses, and an alveolar bone defect. Maxillary sinusitis caused by a bite injury was diagnosed. Because conservative treatment was not effective, tooth extraction was performed under general anesthesia to control the inflammation. The bite wound and maxillary sinusitis improved postoperatively, and the JCOD was completely resolved 3 days after the operation. We surmised that abnormal sensory-motor linkages may have been the main cause of the JCOD. Three years have now elapsed since the surgery, and there has been no recurrence of JCOD and no oral complications. We suggest that JCOD should be treated, because pain and abnormal sensations in the oral region may be involved in its development.

Background aims When cells are exposed to stresses such as mechanical stimuli, they release growth factors and adapt to the surrounding environment H ere, we demonstrated that mechanical stimulation during culture affects the production of osteogenic and angiogenic factors. Methods Human bone marrow derived mesenchymal stromal cells (hMSCs) and human periodontal ligament fibroblasts (HPLFs ) were cultured under cyclic stretch stimulation for 24 h. Collected of the cells and conditioned media (CM), the gene and protein expression levels of osteogenic and angiogenic factors were evaluated. CM was also evaluated for angiogenic activity and calc ification ability. In in vivo study, CM was administered to a mouse calvarial defect model and histologically and radiologically evaluated. Results Quantitative real time polymerase chain reaction results showed that the expression of bone morphogenetic pro tein 2, 4 (BMP 2, 4), vascular endothelial growth factor A (VEGF A), and platelet derived growth factor AA (PDGF AA) was upregulated in the cyclic stretch stimulation group in comparison with the non stretch group in each cell type. Enzyme linked immunosor bent assay results revealed that the expression of BMP 2,4, VEGF A was upregulated in the cyclic stretch group in comparison with the non stretch group in each cell type. Only HPLFs showed significant difference in PDGF AA expression between the cyclic str etch and the non stretch group. Tube formation assay and Alizarin Red S staining results showed that angiogenic activity and calcification ability of CM was upregulated in the cyclic stretch stimulation group in comparison with the non stretch group in eac h cell type. CM was administered to the mouse calvarial defect model. Histological and radiological examination showed that the bone healing was promoted by CM from the cyclic stretch culture group. Immunohistological staining revealed that CM from cyclic stretch group have greater angiogenic effect than CM from the non stretch group. Conclusions These results indicate that osteogenesis was promoted by CM obtained under cyclic stretch stimulation through the increase of angiogenesis in the mouse calvarial defect model.

Objective Owing to variations in the exterior appearances of noncancerous diseases in the oral cavity, clinicians may have difficulty diagnosing oral squamous cell carcinoma (OSCC). Tissue biopsy is confirmatory, but invasive. Therefore, reliable tumor markers for OSCC are required. Here, exosomal Alix (exoAlix) levels were measured in serum/salivary samples from patients with OSCC and healthy controls (HCs). Methods Fifty-seven patients admitted to Nagoya University Hospital from 2017 through 2019 were enrolled, and serum samples (OSCC, n = 29; HC, n = 21) and/or saliva samples (OSCC, n = 23; HC, n = 20) were collected. Exosomal fractions were isolated using ultracentrifugation. ExoAlix levels were measured using enzyme-linked immunosorbent assay. Results Serum/salivary exoAlix levels were significantly higher in patients with OSCC than in HCs. Receiver operating characteristic analyses revealed that sensitivity, specificity, positive predictive value, and area under the curve were 0.345, 1.000, 1.000, and 0.685, respectively, for serum exoAlix and 0.348, 1.000, 1.000, and 0.712, respectively, for salivary exoAlix at optimal cut-off values (serum, 0.205; saliva, 0.193). All tested OSCC tissue sections (n = 21) were immuno-reactive for Alix. Conclusion Serum and salivary exoAlix were identified as potential diagnostic OSCC biomarkers. Serum exoAlix was suitable for prediction of therapeutic responses.

Warthin tumor is a type of salivary gland tumor that occurs mainly in the parotid gland. Warthin tumors rarely occur in multiple regions and simultaneously with oral cancer. We report a case of Warthin tumors that were suspected to be lymph node metastases of maxillary gingival cancer. In early May 2011, a 56-year-old man visited our department because of pain in the gingiva of the upper right jaw. We performed a biopsy of the lesion, and the diagnosis was squamous cell carcinoma (SCC). In early June, we started concurrent chemoradiation therapy (CCRT). We confirmed swelling of the lymph nodes with CT and MRI images and a high standard uptake value (SUV) around the right submandibular lymph nodes and superior internal jugular lymph node on FDG-PET images. However, swollen lymph nodes are not typical manifestations of metastasis; therefore, we applied radiotherapy to only the primary tumor and planned to perform neck dissection after CCRT. According to CT images after CCRT, the size of the primary tumor had drastically changed; however, there was no change in the lymph nodes. Therefore, we performed right total neck dissection as planned. We submitted several lymph nodes for diagnosis, and Warthin tumors were detected in these lymph nodes. As there were no malignancies in the other samples, metastasis was excluded. In the eight years since the patient’s first visit, no SCC or Warthin tumor recurrence has been observed. This case demonstrates that salivary gland tumors can mimic metastases.

Summary Objective Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. Design To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. Results SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. Conclusions Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.

Extracellular vesicles (EVs), several tens to hundreds of nanometers in size, are vesicles secreted by cells for intercellular communication. EVs released from mesenchymal stem cells (MSC-EVs) have the potential to treat multiple diseases. This study aimed to determine the effects of MSC-EVs on bisphosphonate-related osteonecrosis of the jaw (BRONJ), whose pathogenesis and treatment are not yet established. To this end, zoledronic acid (ZOL) was administered to bone marrow cells and fibroblasts in vitro. In vivo, a BRONJ model was produced by administering ZOL to rats and extracting teeth. Each MSC-EV-treated and nontreated group was compared histologically and molecularly. In vitro, the nontreated group showed an increased number of β-galactosidase-positive cells and expression of senescence-associated genes p21, pRB and senescence-related inflammatory cytokines. Conversely, MSC-EV administration decreased the number of senescent cells and expression levels of p21, pRB and inflammatory cytokines. In vivo, in the nontreated group, the socket was partially uncovered by the oral epithelium, leaving an exposed bone. Conversely, in the MSC-EV-treated group, the socket was healed. Besides, in the nontreated group, β-galactosidase-positive cells existed in the socket and colocalized with the CD90 and periostin-positive cells. However, there were few β-galactosidase-positive cells in the MSC-EV-treated group. Furthermore, gene expression of stem cell markers Bmi1 and Hmga2 and the vascular endothelial marker VEGF was significantly increased in the MSC-EV-treated group, compared with that in the nontreated group. These results indicate that MSC-EVs prevent ZOL-induced senescence in stem cells, osteoblasts, and fibroblasts and reduce inflammatory cytokines. Furthermore, administration of MSC-EVs prevented senescence of cells involved in wound healing and the spread of chronic inflammation around senescent cells, thereby promoting angiogenesis and bone regeneration and preventing BRONJ.

Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury. A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined. Immune-related liver injury (≥ Grade 3) occurred in 29 (5.3%) patients (Grade 3, n = 20; Grade 4, n = 8; Grade 5, n = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n = 6 (20.7%); cholestatic, n = 17 (58.6%); and mixed, n = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (≥ Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65–10.80, P = 0.003], and fever over 38 °C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68–14.40, P

Self-injury (SI) can be defined as deliberate harm to one’s own body without conscious suicidal intent. This report describes a case of septicaemia triggered by SI. The patient was a 40 year-old woman, who was diagnosed with Cornelia de Lange syndrome (CdLS). She was hospitalized in a medical long-term care sanatorium and was recently transferred from a familiar sanatorium. She started to bite herself on the mandibular labial alveolar mucosa; this had never been observed. As the self-biting wound gradually increased and the resultant inflammation spread to surrounding tissues, she was referred to our hospital. During the course of treatment, she suffered from septicaemia secondary to aspiration pneumonia. When a case of SI is encountered, clinicians should be aware of the possibility of progression from local infected foci, such as a self-biting wound to septicaemia, and make appropriate interventions at an early stage without underestimating the seriousness of such a condition.

Background Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. Methods A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. Results Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. Conclusions This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.

Background: Surgical site infections (SSI) are associated with increased morbidity and mortality. The purpose of this study was to investigate the ability of perioperative oral management (POM) to reduce the risk of SSI in abdominal surgery. Real-world data collected from 16 Japanese university hospital was reviewed. Methods: The medical records of consecutive 2,782 patients (1,750 men and 1,032 women) who underwent abdominal surgery under general anesthesia in 16 university hospitals were retrospectively reviewed. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. Results: SSI were observed in 275 patients (incidence rate: 9.9%) and POM was delivered in 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group (ECOG) performance status, the American Society of Anesthesiologists (ASA) classification, the surgical site, the preoperative Prognostic Nutritional Index score, POM, the extent of surgery, the operation time, and the amount of intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann-Whitney U-test, p

Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-β-galactosidase-positive cell number and upregulated senescence-related gene (p16INK4a, p19Arf, p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-β) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer.

BackgroundThe clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury.MethodsWe evaluated the characteristics and clinical course of immune-related liver injury in 1087 patients treated with ICIs for advanced malignancies between August 2014 and December 2020. ResultsDuring the follow-up period (median, 270 days), 56 patients (5.2%) had immune-related liver injury (≥Grade 3). The liver-injury patterns were hepatocellular (n = 25, 44.6%), mixed (n = 10, 17.9%), or cholestatic (n = 21, 37.5%), and the median time to onset of liver injury was 36, 85, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (P = 0.036). Corticosteroids were administered to 29 (51.8%) patients. While liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns (mixed, n = 8; cholestatic, n = 7), and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. Conclusion The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differs according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

Background: Postoperative surgical site infections (SSI) can be major complications, which can prolong postoperative treatment. Perioperative oral management (POM) was first covered by Japanese national health insurance system in 2012, and patients that are scheduled to undergo major surgical treatment receive dental and oral management during the perioperative period.Objectives: The purpose of the present study was to investigate the ability of POM to prevent perioperative SSI in patients undergoing abdominal surgery.Methods: The patients’ medical records were retrospectively reviewed, and the effects of POM were investigated in a multicenter analysis involving many cases. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. Results: In total, the cases of 2,782 patients (1,750 males 1,032 females) were reviewed. Of these, POM was performed in 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group (ECOG) performance status, the American Society of Anesthesiologists (ASA) classification, the surgical site, the preoperative Prognostic Nutritional Index score, POM, the extent of surgery, the operation time, and the amount of intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann-Whitney U-test, p