Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism (s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance. They also showed dysbiosis associated with an increased proportion of gram-negative bacteria species and an increased lipopolysaccharide (LPS) level in feces. Intestinal permeability was elevated in association with both epithelial damage and decreased expression levels of tight junction protein zona occludens-1, and thereby LPS levels were increased in serum. For Kupffer cells, the foreign body phagocytic capacity was decreased in magnetic resonance imaging, and the proportion of M1 cells was increased in DKO mice. In vitro experiments showed that the inflammatory response was accelerated in the p62:Nrf2 double-deficient Kupffer cells when challenged with a low dose of LPS. Diet restriction improved the hepatic conditions of NASH in association with improved dysbiosis and decreased LPS levels. The results suggest that in DKO mice, activation of innate immunity by excessive LPS flux from the intestines, occurring both within and outside the liver, is central to the development of hepatic damage in the form of NASH.

Skeletal muscle mass to visceral fat area ratio is an important determinant affecting hepatic conditions of non-alcoholic fatty liver disease.

BACKGROUND: Not only obesity but also sarcopenia is associated with NAFLD. The influence of altered body composition on the pathophysiology of NAFLD has not been fully elucidated. The aim of this study is to determine whether skeletal muscle mass to visceral fat area ratio (SV ratio) affects NAFLD pathophysiology. METHODS: A total of 472 subjects were enrolled. The association between SV ratio and NAFLD pathophysiological factors was assessed in a cross-sectional nature by stratification analysis. RESULTS: When the SV ratio was stratified by quartiles (Q 1-Q 4), the SV ratio showed a negative relationship with the degree of body mass index, HOMA-IR, and liver stiffness (Q 1, 8.9 ± 7.5 kPa, mean ± standard deviation; Q 2, 7.5 ± 6.2; Q 3, 5.8 ± 3.7; Q 4, 5.0 ± 1.9) and steatosis (Q 1, 282 ± 57 dB/m; Q 2, 278 ± 58; Q 3, 253 ± 57; Q 4, 200 ± 42) measured by transient elastography. Levels of leptin and biochemical markers of liver cell damage, liver fibrosis, inflammation and oxidative stress, and hepatocyte apoptosis were significantly higher in subjects in Q 1 than in those in Q 2, Q 3, or Q 4. Moreover, fat contents in femoral muscles were significantly higher in subjects in Q 1 and the change was associated with weakened muscle strength. In logistic regression analysis, NAFLD subjects with the decreased SV ratio were likely to have an increased risk of moderate-to-severe steatosis and that of advanced fibrosis. CONCLUSIONS: Decreased muscle mass coupled with increased visceral fat mass is closely associated with an increased risk for exacerbating NAFLD pathophysiology.

Non-small-cell lung cancer metastasis to the oral cavity: A case report.

We herein report an unusual occurrence of lung cancer metastasis to the oral cavity, reflecting the progression of the primary malignancy. A biopsy of oral lesions should always be performed, even of those located in uncommon sites, in patients with a history of uncontrolled lung cancer. Although this is a rare occurrence, our patient exhibited characteristics suggestive of oral metastasis from lung cancer, namely presence of lung adenocarcinoma, development of oral metastasis during the clinical course of the disease, accompanying multiple metastatic lesions, including to the brain and abdomen, and rapid fatal progression after the manifestation of oral metastasis. It is important to acknowledge the possibility of metastasis to the oral cavity in lung cancer patients with extensive metastases. Prompt diagnosis by biopsy of the lesion is required to establish the correct diagnosis.

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.

BACKGROUND: N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the ß1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. METHODS: Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. RESULTS: Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. CONCLUSIONS: GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.

Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis.

N-acetylglucosaminyltransferase V (GnT-V), an enzyme with a key role in the branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of many solid tumors. Here we searched for correlations between the clinical features of patients with oral squamous cell carcinoma (OSCC) and GnT-V expression in the tumor, and we studied the feasibility of using GnT-V as a marker for oral cancer prognosis. Samples from 68 patients with OSCC were examined by immunohistochemistry using antibodies against GnT-V. Correlations between the expression level of GnT-V in the tumor and patient clinical features were statistically analyzed. Positive GnT-V expression was found in 48 cases (70.6%), and negative GnT-V expression was found in 20 cases (29.4%). Negative GnT-V expression was associated with mode of invasion by multiple logistic regression analysis (OR: 3.605; P = 0.048). Biological characteristics of tumors and the Ki-67 labeling index were higher in tumors with negative GnT-V expression than in those with positive GnT-V expression, although the difference was not significant (P = 0.176). Patients with negative GnT-V expression had significantly shorter survival than those with tumors having positive GnT-V expression (5-year survival rate, 58.2% and 86.5%, respectively; P = 0.025). Negative GnT-V expression was a significant unfavorable prognostic factor for OSCC (hazard ratio, 4.246; P = 0.045). The loss of GnT-V expression is a likely indicator of tumors with high potential of tumor invasion and poor prognosis in OSCC patients.

Prognosis for gingival carcinomas with a delayed diagnosis after dental extraction.

PURPOSE: In gingival squamous cell carcinoma (GSCC), the association between survival and previous dental extraction (DE) is controversial. The purpose of this study was to investigate the prognosis for patients in whom GSCC was detected after DE was performed. PATIENTS AND METHODS: DE for GSCC tumor symptoms was performed in 19 patients before diagnosis (DE group) and not in 58 patients (non-DE group). The clinical features, characteristics, and prognosis were evaluated statistically between the 2 groups. RESULTS: The interval from DE to the first hospital visit was 1.1 to 97 weeks (median, 7.3 weeks). There was no significant difference in tumor status, node status, local recurrence, pathologically positive lymph nodes, or distant metastasis between the DE and non-DE groups. Bone invasion was observed radiographically in 6 patients with mandibular GSCC in the DE group (100%) and 13 in the non-DE group (68.4%). There was a significant difference in bone invasion between the DE and non-DE groups (P < .01). Segmental mandibulectomy was performed in 11 patients (84.6%) in the DE group and 21 patients (61.8%) in the non-DE group. Extent of resection tended to be larger for the DE group. The 5-year overall survival rate was 84.6% for the DE group and 65.8% for patients with mandibular GSCC in the non-DE group. For maxillary GSCC, the survival rates differed significantly between groups (33.3% in DE group and 73.7% in non-DE group). CONCLUSIONS: For mandibular GSCC, the resection field was appropriate for the extent of bone invasion after DE and the prognosis was similar to that in the non-DE group. For maxillary GSCC, a broad surgical field is suggested because of the potential for rapid spread in cancellous bony trabeculae.

Neuroleptic malignant syndrome in a patient with tongue cancer: a report of a rare case.

Background. Neuroleptic malignant syndrome (NMS) is a rare but life-threatening complication of neuroleptic drugs, which are used widely in head and neck cancer (HANC) patients who develop delirium. Methods and Results. Postoperative delirium in a 39-year-old man with tongue cancer was treated with haloperidol and chlorpromazine. Three days after the first administration of antipsychotics, the patient exhibited elevated body temperature, autonomic and extrapyramidal symptoms, and impaired consciousness. A definitive diagnosis was made using the research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were immediately discontinued. The patient was given dantrolene and bromocriptine to treat the NMS. The patient's hyperthermia, elevated creatinin kinase (CK), and muscle rigidity improved gradually, with all symptoms of NMS resolving completely by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for early signs of NMS and use antipsychotics conservatively to avoid NMS and its potentially fatal outcome.

Radiation-induced carotid artery stenosis in a patient with carcinoma of the oral floor.

Radiation-induced carotid artery stenosis (RI-CS), a life-threatening condition, can occur after external radiation for head and neck cancer. We here describe a case of asymptomatic RI-CS in a 73-year-old patient treated with chemoradiotherapy and radical neck dissection for a basaloid squamous cell carcinoma of the oral floor. Stenosis of the left carotid artery, diagnosed as RI-CS, showed on an MRI performed 1.5 years after radiotherapy. Blood from the left side of the anterior cerebral artery and the middle anterior artery was flowing to the brain through the anterior and posterior communicating arteries, so no stent surgery or other treatment was necessary. The cancer has not recurred during approximately 5 years of followup after radiotherapy, and the patient has had no adverse effects from the RI-CS since it was diagnosed 3.5 years ago. This case emphasizes the necessity of early scrutiny for RI-CS in patients given radiotherapy for oral cancer.

Presurgical orthopedic treatment ameliorates postoperative nasal deformity after cheiloplasty.

We assessed the postoperative nasal form and symmetry after presurgical use of a Hotz plate (HP) in patients with unilateral complete cleft lip and palate (UCLP). The subjects were 28 infants with UCLP who underwent cheiloplasty. Of these subjects, 14 underwent presurgical orthopedic treatment using the HP (HP group) and 14 underwent the same treatment without the HP (non-HP group). Photographic records were obtained 1 and 6 months after cheiloplasty, and the results of anthropometric analysis were compared between the 2 groups. The nasal inclination and the ratio of the width of the nasal base to the total width of the nose were significantly improved in the HP group compared with the non-HP group at both postoperative time points. Thus, presurgical use of the HP significantly improved the nasal asymmetry and deformity in UCLP patients after primary cheiloplasty and nasal repair.

Presurgical nasoalveolar molding orthopedic treatment improves the outcome of primary cheiloplasty of unilateral complete cleft lip and palate, as assessed by naris morphology and cleft gap.

We evaluated the effects of presurgical nasoalveolar molding (NAM) with an orthopedic appliance and compared them with a passive orthopedic method (Hotz plate, HP), focusing on the naris morphology and width of the alveolar and palate cleft gap. The subjects were 28 unilateral complete cleft lip and palate patients treated with primary cheiloplasty at Tsukuba University Hospital from 2004 to 2011. Thirteen patients were treated preoperatively with NAM (NAM group), and 15 with HP (HP group). The surgical outcome was assessed according to left-right naris symmetry, as measured by the area ratio, perimeter ratio, aspect a/u ratio (aspect ratio of the affected side/aspect ratio of the unaffected side), and Hausdorff distance. In addition, the alveolar and palate cleft width was measured at the times of orthopedic plate setting and primary cheiloplasty. The aspect ratio was significantly smaller in the NAM group than in the HP group before the operation. In both groups, the aspect ratio, perimeter ratio, and Hausdorff distance were significantly smaller after the operation than before. The width of the alveolar and palate cleft gap was significantly narrowed in the NAM group, and the cleft gap at the initiation of NAM correlated significantly with the Hausdorff distance after cheiloplasty. We found that NAM improved the form of the naris after primary cheiloplasty and decreased the palate cleft gap more effectively than HP and that the width of the palate cleft gap was correlated with the surgical outcome of the naris.

A novel method for evaluating postsurgical results of unilateral cleft lip and palate with the use of Hausdorff distance: presurgical orthopedic treatment improves nasal symmetry after primary cheiloplasty.

OBJECTIVE: To evaluate surgery results, we established a novel method to digitize nasal morphology with the use of Hausdorff distance and analyzed nose morphology after cheiloplasty. STUDY DESIGN: We evaluated the naris after primary cheiloplasty of 30 unilateral cleft lip and palate patients. Similarity between left and right sides was assessed by visual evaluation, area ratio, perimeter ratio, aspect a/u ratio, and Hausdorff distance. The postoperative naris morphology was also compared between 15 patients treated with a Hotz plate before surgery and 15 not treated. RESULTS: Significant correlation with visual evaluation was found for Hausdorff distance. For the groups with and without Hotz plate treatment, the visual evaluation was higher and Hausdorff distance significantly lower in the treated group. CONCLUSIONS: The morphologic measurement obtained using the Hausdorff distance was the closest to visual evaluation, and assessment using Hausdorff distance suggested that using a Hotz plate helps retain the symmetry of the nares after cheiloplasty.

Angiosarcoma of the scalp diagnosed by the presence of neck inflammation: a case report.

Angiosarcoma is an uncommon malignancy, which spread out from the endothelial cells of vessels. Scalp angiosarcoma with cervical lymph node metastasis is particularly rare. This article describes a rare case of angiosarcoma of the scalp, presenting as neck inflammation. Imaging procedures such as computed tomography (CT), magnetic resonance image (MRI) and ultrasonography (US) were not sufficient to diagnose this case. A needle biopsy provided an effective and accurate diagnosis of cervical lymph node metastasis. Additional observation and physical examination was required to diagnose the origin of the primary cancerous lesion. Once the angiosarcoma diagnosis was confirmed histologically, sequential weekly and monthly docetaxel (DTX) treatment was effective in preventing reoccurrence. Nonetheless, the optimization of angiosarcoma treatment remains a future goal. Although patients generally describe pain and swelling at the primary lesion site, this patient complained only of painful neck inflammation, without any indication of pain or swelling of the scalp. A revised diagnostic protocol should note that cervical lymph node metastasis of unknown primary origin may result from angiosarcoma of the scalp.

Real-time tissue elastography for the diagnosis of lymph node metastasis in oral squamous cell carcinoma.

We compared conventional ultrasound (US) B-mode, color Doppler and elastographic assessment of lymph node (LN) stiffness against pathological findings from surgical samples, to determine the most useful factors for identifying LN metastases. Seventy-one LNs in 19 patients with oral squamous cell carcinoma (OSCC) were examined. Using our new system, elastography images were scored from 1-5. The score 1-4 were correlated with the blue area of each LN, which indicated increased stiffness: (1) none; (2) < 50%; (3) 50%; or (4) > 50%. A score 5 indicated central necrosis and did not correlate with the blue area. We found significant differences in minimal diameter, shape index, margin, internal structure, hilus presence or absence, elastography score and percentage of blue area between metastatic and nonmetastatic LNs. Stepwise regression analysis identified elastography score 3-5 as an independent significant LN metastatic factor, suggesting that our scoring system may be useful for accurately diagnosing metastatic LNs.

Basal cell adenoma arising in a minor salivary gland of the palate.

BACKGROUND: Basal cell adenoma is a benign neoplasm of the salivary glands. This tumor usually arises in the major glands, with the parotid being the most frequent site of occurrence, while it is rare in the minor salivary glands. We report a case of basal cell adenoma of a minor salivary gland on the palate. CASE: The patient was a 68-year-old man. Intraoral examination revealed a mass measuring 20 × 20 mm that was elastic-hard, dark violet, non-ulcerated, and covered the normal mucosa. Computed tomography scan and magnetic resonance imaging (MRI) both showed a mass situated in front of the soft palate. The T1-weighted MRI revealed tumor isointensity, and the T2-weighted image showed tumor hyperintensity. The clinical diagnosis was palate tumor, and excision was performed under general anesthesia. Histopathological examination revealed that an encapsulated mass had grown under the epithelium and indicated a diagnosis of basal cell adenoma. DISCUSSION: Although no recurrence has been detected in the 3 years and 6 months of follow up, there was a case of malignant transformation of a basal cell adenoma reported. Therefore, careful follow-up observation will continue to be important.

Inflammatory pseudotumor: report of a case in the mandible.

BACKGROUND: Intraoral inflammatory pseudotumor (IPT) is a rare, benign non-neoplastic lesion that presents as a rapidly growing mass with aggressive behavior, which can be mistaken for a malignant process. CASE REPORT: This article presents a rare case of IPT of the mandible in a 70-year-old male patient. Examination of the oral cavity revealed a hemorrhagic soft mass of the mandibular region. The patient was treated with surgery. Histologic examination of the resected specimen showed proliferation of fascicular spindle cells and a dense, chronic inflammatory cell infiltrate consisting of neutrophils, eosinophils, and lymphocytes. Immunohistochemically, the spindle cells expressed vimentin, α smooth muscle actin, and CD68, indicating a diagnosis of IPT. DISCUSSION: IPT is an unusual benign pathology in the oral and maxillofacial area. Because of its aggressive clinical and radiological features, it can be mistaken for a malignancy. We suggest that oral and maxillofacial surgeons should be aware of the specific features of IPT to avoid unnecessary aggressive treatments such as a radical resection.

Cheilitis glandularis: two case reports of asian-Japanese men and literature review of Japanese cases.

Cheilitis glandularis (CG) is a rare disorder characterized by swelling of the lip with hyperplasia of the labial salivary glands. CG is most frequently encountered in the lower lip, in middle-aged to older Caucasian men; however Asian cases were rarely reported. In this paper we present two cases of CG in Asian-Japanese men. One was a 23-year-old male with CG of the superficial suppurative type. The other was a 54-year-old male with deep suppurative type. We also reviewed the Japanese cases of CG in the literature and discussed about clinical feature of Japanese CG.

Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: Although dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear. STUDY DESIGN: This study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs and to leave the asymptomatic ones untreated, regardless of their impacted position. RESULTS: Eighty-seven ITMs were observed in 35 patients. The ITMs were in the maxilla of 25 patients and the mandible of 28 patients. Dental extraction of 7 teeth was performed in 6 patients without complications. All of the patients received the scheduled HSCT therapy and none experienced odontogenic infection while myelosuppressed. CONCLUSIONS: This management plan for ITM appears to be appropriate for pre-HSCT patients. Moreover, the experienced dental provider is suggested as a necessary and valuable part of the HSCT team.

Treatment of localized oral MALT lymphoma by rituximab: a case report.

INTRODUCTION: Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoma tissue (MALT) among intraoral malignant lymphomas is very rare. Moreover, no case of oral MALT lymphoma treated with monoclonal antibody therapy has been reported. DISCUSSION: We describe a case of MALT lymphoma arising in an 87-year-old Japanese woman under the buccal mucosa that was successfully treated with rituximab, a chimeric monoclonal antibody against the B cell-specific antigen CD20. Currently, 5 months after completing treatment, the patient is alive and has partial regression of the tumor.

Treatment for lung metastasis from head and neck squamous cell carcinoma: a preliminary study of docetaxel.

OBJECTIVES: The aims of the study were to investigate the prognosis of patients with lung metastasis after treatment for head and neck squamous cell carcinoma (HANSCC) and to preliminarily evaluate the efficacy and toxicity of docetaxel (DOC)-based chemotherapy. MATERIALS AND METHODS: The effectiveness of the chemotherapy was evaluated retrospectively according to the tumor response rate and survival time post-metastasis. Thirty patients were enrolled in the study. Twenty-seven have died, two are living, and one was lost during follow-up. Nineteen patients were treated for lung metastasis with chemotherapy. DOC-based chemotherapy was given to seven patients and non-DOC-based chemotherapy to 12. RESULTS AND DISCUSSION: The response rate was 28.6% for the first administration of DOC-based chemotherapy, but only 8.3% for the non-DOC-based chemotherapy. Thus, DOC-based chemotherapy had a better response rate for lung metastases than other chemotherapy agents tested. Although the sample size was small, DOC seems to shrink or inhibit the growth of lung metastases in patients with primary HANSCC.