Comparison of the 8th edition of TNM staging of oral cancer with the 7th edition and its prognostic significance using clinical depth of invasion and extranodal extension.

OBJECTIVES: The 8th edition of the International Union Against Cancer Control/American Joint Committee on Cancer Staging System introduced depth of invasion (DOI) and extranodal extension (ENE) into the staging of oral cavity cancer. We evaluated the prognostic ability of this new staging system compared with the 7th edition using clinical DOI (cDOI) and clinical ENE (cENE). MATERIALS AND METHODS: We retrospectively reviewed and restaged 2,118 patients with oral squamous cell carcinoma treated between 2001 and 2018 using cDOI and cENE. Overall and disease-specific survival were used as endpoints to compare the prognostic outcomes of the 7th and 8th editions using Harrell's concordance index (C-index). RESULTS: In total, 305 (14.4 %) cases were upstaged in the T category, 85 (4.0 %) cases were upstaged in the N category, and 280 (13.2 %) cases were upstaged in the overall TNM stage. The introduction of the cDOI increased the C-index and hazard ratio (HR) for each T category. The introduction of cENE increased the N3b category of 85 cases, bringing the total to 94 cases, thereby widening the differences between each N category. In the 8th edition, the C-index and HR for overall TNM stage increased, and the discrimination between stage groups improved. CONCLUSIONS: The 8th edition of the TNM clinical staging system using cDOI and cENE predominantly identified patients with a high mortality rate, thus improving the ability to discriminate and prognosticate oral cancer.

The Impact of Pretreatment Low Body Mass Index on Cause-Specific Mortality in Patients with Squamous Cell Carcinoma of the Oral Cavity.

The association between the pretreatment body mass index (BMI) and oral squamous cell carcinoma (SCC) outcomes is controversial. We aimed to examine the association between BMI and cause-specific mortality due to cancer of the oral cavity and patterns of failure that correlate with increased mortality. We enrolled 2,023 East Asian patients in this multicenter cohort study. We used the cumulative incidence competing risks method and the Fine-Gray model to analyze factors associated with cause-specific mortality, local recurrence, regional metastasis, and distant metastasis as first events. The median follow-up period was 62 mo. The 5-year cause-specific mortality for patients with underweight was 25.7%, which was significantly higher than that for patients with normal weight (12.7%, P < 0.0001). The multivariate model revealed that underweight was an independent risk factor for cause-specific mortality and regional metastasis (P < 0.05). Moreover, patients with underweight displayed a 51% and 55% increased risk of cause-specific mortality and regional metastasis, respectively, compared with their normal weight counterparts. Local recurrence was not associated with the BMI categories; however, the incidence of distant metastasis inversely decreased with BMI value. In summary, being underweight at diagnosis should be considered a high-risk mortality factor for oral SCC.

Short ramus reconstruction for hemi-mandibulectomy defect: Case reports.

Reconstruction of the mandible following hemimandibulectomy is difficult and complex. The appropriate approach to condylar reconstruction remains controversial. In this report, the authors propose the concept of "short ramus reconstruction" after hemimandibulectomy. In this technique, a neocondyle is constructed around the base of the condyle to avoid trismus and ankylosis. Four patients underwent short condylar reconstruction using fibula free flaps. Post-surgery, no patient developed trismus or ankylosis. Centric occlusion, good masticatory function, and favourable aesthetic outcomes were achieved in all cases. "Short ramus reconstruction" is a simple and convenient method to reconstruct the mandible following hemimandibulectomy.

[Pneumopericardium 4 Years after Surgery of Thymic Cancer].

A 67-year-old man had undergone thymectomy with partial resection of the left upper lobe and pericardium for thymic cancer. Four years later, he visited our hospital due to chest pain. Chest computed tomography revealed pneumopericardium. Nine months later, surgical treatment was performed due to the development of the left pneumothorax. Air leak was found from the bulla which was partially incarcerated into the pericardial space.

Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction of Tongue Cancer: A Case Report.

Breast cancers are the most common cancers in women. However, breast cancer occurring in a pectoralis major myocutaneous flap is extremely rare. This article describes a case of breast cancer occurring in such a flap used for reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a fine-needle aspiration biopsy specimen taken from the lesion suggested glandular carcinoma. The patient was diagnosed with breast cancer in the neck area of the flap and tumor excision was performed. Histologic examination of the excised tumor showed tumor cells arranged in cords, with tubular and cribriform carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to the neck with a total radiation dose of 50 Gy. Furthermore, the patient received oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor-positive breast malignancy. One year after surgery, the patient was alive with no evidence of disease. Including this case, only 2 cases of breast cancer in a pectoralis major myocutaneous flap used for reconstruction in the head and neck region have been reported.

Efficacy of prolonged ingestion of Lactobacillus acidophilus L-92 in adult patients with atopic dermatitis.

To evaluate the safety and efficacy of prolonged ingestion of Lactobacillus acidophilus L-92 (L-92) on skin symptoms in adult atopic dermatitis (AD) patients, a placebo-controlled double-blinded parallel-group comparison study was performed. This included daily administration of heat-killed and dried L-92 or placebo for 24wk in 50 AD patients who were 16yr old or older. The severity of skin symptoms was evaluated at baseline and at 4, 8, 12, 16, 20, and 24wk during the intervention using the investigator global assessment, eczema area and severity index, and scoring atopic dermatitis. Serum cytokine and blood marker levels were also measured at baseline and at 4, 8, 16, and 24wk during the intervention. No adverse events were reported during the study period. Compared with the placebo group, the L-92 group showed significant decreases in investigator global assessment, eczema area and severity index, and scoring atopic dermatitis. Subjective symptoms in adult AD patients were reduced by intake of L-92. Furthermore, it was suggested that sustained ingestion of L-92 resulted in suppression of scratching behavior and maintenance of remission status of skin symptoms. Sixteen weeks after the study commenced, a significant decrease in lactate dehydrogenase and a significant increase in transforming growth factor-ß were observed in the L-92 group compared with the placebo group. In the L-92 group, a significant elevation of IL-12 (p70) level at the end of treatment period compared with before the treatment was observed. This study suggested that L-92 suppresses type-2-helper-T-cell-dominant inflammation by activating regulatory T cells and type 1 helper T cells.

Totally thoracoscopic surgery and troubleshooting for bleeding in non-small cell lung cancer.

BACKGROUND: Although accumulating data support the feasibility and efficacy of video-assisted thoracic surgery anatomic resection, few studies have reported on intraoperative complications, such as vessel injury. The purpose of this study was to evaluate intraoperative vessel injury and to analyze troubleshooting. METHODS: Twenty-six of 557 patients with non-small cell lung cancer who underwent thoracoscopic anatomic lung resection were identified as having intraoperative vessel injury between January 2004 and December 2011. The injured portion, devices used, recovery approach, and hemostatic procedure were analyzed. The perioperative outcomes in patients with and without vessel injury were compared. RESULTS: The most commonly used devices were ultrasonic coagulation shears in 9 cases, followed by scissors in 5 and an endostapler in 4. Seventeen of the 26 cases were injured at the branches of the pulmonary artery, and the others were at major vessels. Half of the patients were converted to thoracotomy, and 6 were treated by minithoracotomy. Hemostatic procedures were primary closure in 17 and sealant in 7. The perioperative outcomes, including operative time and blood loss, were significantly different between the two groups, but duration of chest tube drainage, length of hospital stay, and morbidity rate were not. No mortality was identified in the patients with vessel injury. CONCLUSIONS: Video-assisted thoracic surgery anatomic resection was feasible and safe, regardless of the intraoperative vessel injury. Although surgeons should pay attention to avoid unexpected bleeding, the magnitude of injury and effectual step-by-step management should lead to a safe operation.

Basaloid squamous cell carcinoma of the mandible: report of two cases.

Basaloid squamous cell carcinoma is a rare aggressive malignancy that is a distinct variant of squamous cell carcinoma. This report presents 2 cases of basaloid squamous cell carcinoma in the gingiva. Case 1 is a 55-year-old Japanese man who presented with a painful, red, and irregular mass on the left mandibular gingiva. Case 2 is a 65-year-old Japanese man who presented with a painless mass on the right mandibular gingiva. Both tumors were diagnosed histopathologically as basaloid squamous cell carcinoma. In case 1, the patient underwent wide resection of the gingival tumor with a partial mandibulectomy and ipsilateral functional neck dissection. The mandible was reconstructed with a titanium plate and forearm flap. In case 2, the patient underwent wide resection of the gingival tumor after local irradiation (60 Gy). At the time of writing, both patients remained in good health and free of disease.

Epstein-Barr virus-positive Hodgkin lymphoma-like earlobe lymphoid infiltrate: case report.

Hodgkin lymphoma (HL) is a malignancy of the lymph system usually occurring on the lymph nodes. A 57-year-old Japanese woman presented with the chief complaint of an enlarging tumor of the left ear. An excisional biopsy was taken, and histological examination showed a mixed infiltration of cells, including Reed-Sternberg cells and their mononuclear forms against a background of small lymphocytes. Reed-Sternberg cells were CD15, CD20, CD30, Ki-67, MUM-1, CD45, EMA, and Epstein-Barr virus-encoded small RNA was detected by in situ hybridization. We diagnosed this tumor as a skin infiltration with a lymphocyte-rich classical HL pattern. Skin involvement of HL is most often a secondary phenomenon representing a rare late manifestation of disease dissemination; however, we could not detect any evidence of systemic lesion for 6 months after the initial presentation. A case of HL only involving the skin was reported by several past reports, which termed it primary cutaneous HL. But, it is still controversial whether HL initially occurs on the skin because a diagnostic gray zone exists between HL, some non-HL entities, and nonneoplastic lymphoid infiltrates. Clinical and histological features of this case suggest that the skin will become a primary site of HL.

The incidence of internal malignancies in autoimmune bullous diseases.

Autoimmune bullous diseases are classified into pemphigus and pemphigoid. Pemphigus is designated as incurable disease by the Ministry of Health, Labor and Welfare, and it is said that pemphigus is difficult to care and can be fatal. The clinical course of bullous pemphigoid (BP) is better than that of pemphigus. However, as to the incidence of internal malignancies, it is well known that there is a significant difference between the two diseases. As the incidence of internal malignancies is high in BP, it is described in textbooks that patients with BP should be followed by a detailed screening for internal malignancies. We investigated the incidence of internal malignancies in 204 Japanese patients with autoimmune bullous disease who visited Tokai University Hospital in Kanagawa, Japan. We found that the incidence of internal malignancies was 11.2% in patients with pemphigus and 10.4% in patients with BP. Among pemphigus variants, the incidence was as high as 20% for pemphigus erythematosus. No relationship was found between malignancies and the severity of the autoimmune bullous diseases. Therefore it is clinically important to carry out a detailed screening for internal malignancies in patients with pemphigus as well as in patients with BP.

A case of implantation dermatosis that formed a tumor.

A 51-year-old man visited our hospital complaining of a tumor located above his lip. He had been hit on his upper left lip by a chopstick holder 2 months previously. The lesion turned into a tumor and gradually enlarged. The tumor was well circumscribed, smooth and covered with reddish, partially milk-white skin. During surgery to remove the tumor, a piece of a chopstick was found in the subcutaneous tissue, and a diagnosis of implantation dermatosis (ID) was made. On histology, the tumor appeared as an abscess that had increased fibroblasts, small vessels and a large number of neutrophils. In the Japanese published work, we found 86 cases of ID; three were similar to our case and had been clinically diagnosed as adnexal tumors. There were also six cases that showed abscess formation similar to our case on histology. In a survey of the published work from other countries, there were 44 ID cases. There were no common features found among the cases reported in the published work.

A case of superficial angiomyxoma.

We report a case of a 19-year-old man who showed a brownish, elastic-soft, multilocular, pedunculated, solid tumor (10 × 6 × 6 cm), with scale crust and erosion, on the medial side of the right thigh. The histopathology of a specimen removed completely revealed a tumor that was located between the middle layer of the dermis and the subcutaneous fatty tissue, was filled with a mucoid material, and was surrounded by a fibrous tissue. The tumor consisted of small thin-walled blood vessels and spindle-shaped or stellate tumor cells without cytological atypia in addition to the mucoid material. Immunohistochemistory revealed that the tumor cells express the vimentin stain. Based on these clinical and histologic findings, we diagnosed the skin condition as superficial angiomyxoma.

Feasibility of modified DLQI-based questionnaires for evaluation of clinical efficacy of herbal medicine in chronic skin diseases.

BACKGROUND: The efficacy of herbal medicines is thought to be ambiguous. The quality of life (QOL) of patients has been well-recognized as an useful measurement and we thought it to be a measurement of the efficacy of herbal medicine. OBJECTIVE: The aim of this study was to examine the feasibility of modified DLQI-based questionnaires in evaluating the efficacy of herbal drugs in chronic skin diseases. METHODS: 19 in-patients with chronic skin diseases were selected and treated by the herbal medicines just added on the previous drugs. By using the QOL-sheet, the patients' QOL before and after herbal treatments were converted to scores and we examined the scores to be a useful measurement. The QOL-sheet was made referring to the dermatology life quality index (DLQI) with our original questions and visual analogue scale (VAS) in Japanese. RESULTS: The herbal drugs were effective as the treatment with significant difference (P < 0.05) at clinical impression, DLQI and VAS. No significant differences of correlation between clinical impression, DLQI/DLQI with AQ and VAS/VAS with AQ was proved (P > 0.05). CONCLUSIONS: The QOL-sheet scored both by DLQI and by VAS may be useful to evaluate the efficacy of herbal medicines. However it may be necessary to reconsider the contents of our original questions.

Delivery of cytolethal distending toxin B induces cell cycle arrest and apoptosis in gingival squamous cell carcinoma in vitro.

The cytolethal distending toxin (Cdt) from Actinobacillus actinomycetemcomitans consists of three proteins, CdtA, CdtB, and CdtC, which are responsible for cell cycle arrest and apoptosis. In the present study, local delivery systems of recombinant CdtB and CdtB-expressing plasmid were established using Ca9-22, human gingival squamous cell carcinoma cell line. When CdtB was delivered to Ca9-22 cells using a BioPORTER, a 32-kDa protein was detected by Western blotting, and G2 cell cycle arrest and apoptosis occurred. In addition, the CdtB delivered upregulated the expression of phosphorylated p53 and the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) in Ca9-22 cells, suggesting that these intracellular molecules might contribute to the induction of G2 cell cycle arrest and apoptosis. When the CdtB-expressing plasmid was transfected into Ca9-22 cells by lipofection or electroporation, CdtB (32 kDa) was clearly detected. Further, TdT-mediated dUTP nick end labeling positive cells were observed after transfection of the CdtB-expressing plasmid. These findings indicated that delivery of the CdtB protein and transfection of the cdtB gene induced cell cycle arrest and apoptosis in Ca9-22 cells in vitro, and we conclude that it may be possible to induce apoptosis in human gingival squamous cell carcinoma by electroporation of the cdtB gene.

Involvement of caspase activation through release of cytochrome c from mitochondria in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans.

We previously reported that infection with the periodontopathic bacterium Actinobacillus actinomycetemcomitans induced apoptosis in a mouse macrophage cell line J774.1. In the present study, we examined the involvement of cytochrome c and caspases in the induction of apoptosis in A. actinomycetemcomitans-infected J774.1 cells. Following infection, the expression levels of cytochrome c, and cleaved forms of caspase-3 and caspase-9 in the cells were examined using immunoblot analysis. Cytochrome c was released from mitochondria into the cytoplasm after A. actinomycetemcomitans-infected J774.1 cells were cultured for 6 h, and caspase-3 and caspase-9 were found to be cleaved forms in the cells. Further, caspase-9 activity was markedly increased, and phosphorylated p53 was detected in the cells 30 h following infection. These results suggest that apoptosis in A. actinomycetemcomitans-infected J774.1 cells is regulated by the release of cytochrome c from mitochondria into cytoplasm and the subsequent activation of caspases through phosphorylation of p53.

Myocardial infarction in a patient with severe aortic stenosis and normal coronary arteriograms: involvement of the circumferential subendocardial wall of the left ventricle.

A case of severe aortic stenosis with normal coronary arteriograms was associated with myocardial infarction involving the circumferential subendocardial wall of the left ventricle. The infarct was caused solely by the severe aortic stenosis and resulted from the extreme disparity between myocardial oxygen supply and demand.

Effect of cilostazol on the ventricular escape rate and neurohumoral factors in patients with third-degree atrioventricular block.

STUDY OBJECTIVES: This study assessed whether the antiplatelet agent cilostazol, which has potent cyclic nucleotide phosphodiesterase type-3 inhibitory activity, affects the ventricular escape rate and neurohumoral factors in patients with third-degree atrioventricular block. DESIGN: Prospective, but nonrandomized, study. SETTING: Cardiology division of an acute care hospital. PATIENTS: We studied 12 patients with third-degree intra-His or infra-His atrioventricular block who were in functional class II or III of the New York Heart Association classification. None of the patients had experienced Adams-Stokes attacks. INTERVENTIONS: These patients were given cilostazol orally at a dose of 200 mg daily for at least 1 week. MEASUREMENTS AND RESULTS: Before and after treatment with cilostazol, continuous 24-h ECG monitoring and measurement of plasma natriuretic peptide concentrations were performed. Cilostazol significantly increased the mean (+/- SEM) total 24-h QRS count from 57,300 +/- 2,800 to 74,400 +/- 3,200 beats (p = 0.001) and significantly decreased the maximum geometric mean R-R interval over a 24-h period from 1,900 ms (95% confidence interval [CI], 1,700 to 2,100 ms) to 1,600 ms (95% CI, 1,400 to 1,900 ms; p = 0.02), although none of the patients showed the abolishment of the atrioventricular conduction abnormalities. The total 24-h count of premature ventricular beats was not different before treatment (15 beats; 95% CI, 5 to 44 beats) and after treatment (12 beats; 95% CI, 5 to 30 beats; p = 0.57). Treatment with cilostazol significantly decreased the concentration of plasma atrial natriuretic peptide from 88 pg/mL (95% CI, 49 to 160 pg/mL) to 51 pg/mL (95% CI, 32 to 80 pg/mL; p = 0.007) and of brain natriuretic peptide from 166 pg/mL (95% CI, 71 to 389 pg/mL) to 77 pg/mL (95% CI, 30 to 178 pg/mL; p = 0.02). CONCLUSIONS: Cilostazol significantly increased the ventricular escape rate and significantly decreased the level of circulating natriuretic peptides. Thus, cilostazol could be safely given to selected patients over the short term with third-degree atrioventricular block.

Brain natriuretic peptide as a risk marker for incident hypertensive cardiovascular events.

We examined the effects of aging and hypertensive left ventricular hypertrophy on the plasma level of brain natriuretic peptide (BNP), and assessed BNP as a risk marker for incident hypertensive cardiovascular events. One hundred and eighty-five hypertensive patients were echocardiographically divided into a hypertensive group with normal left ventricular mass (n=96; age range, 37-86 years; left ventricular mass, 97+/-14 g/m2) and a hypertensive group with left ventricular hypertrophy (n=89; 37-90 years; 140+/-20 g/m2). Forty-four normotensive subjects served as the normotensive group (32-84 years; 91+/-15 g/m2). We examined the association of age with BNP in the three groups and also evaluated BNP as a risk marker for incident cardiovascular events by following up all patients for 40 months. All three groups demonstrated a significant positive relationship between age and BNP. The slope of the relation between age and BNP was steepest in the hypertensive group with left ventricular hypertrophy (p<0.0001 vs. the other two groups). Multiple regression analysis revealed that age, pulse pressure and left ventricular mass index were significantly associated with the increase in BNP. Multivariate Cox proportional hazards regression analysis, which was used to assess the potential association of age, pulse pressure, left ventricular mass index and BNP with the cardiovascular events during follow-up, revealed the highest correlation between BNP and incident cardiovascular events (risk ratio=1.011; p=0.0011). BNP, which is synergistically increased with aging and left ventricular hypertrophy, may be an important risk marker for hypertensive cardiovascular events.

Occurrence of transient U-wave inversion during vasospastic anginal attack is not related to the direction of concurrent ST-segment shift.

STUDY OBJECTIVES: We sought to assess the incidence of transient U-wave inversion during vasospasm of the left anterior descending coronary artery (LAD) with ST-segment depression as opposed to that with ST-segment elevation. DESIGN: Retrospective study. SETTING: Cardiology division of acute-care hospitals. PATIENTS: We studied 49 patients with vasospastic angina whose vasospasm was induced in the LAD, not in the left circumflex coronary artery, by intracoronary injection of acetylcholine. MEASUREMENTS AND RESULTS: The ECG traces obtained during acetylcholine-induced vasospasm of the LAD were examined. Based on the direction of ST-segment shift, the patients were categorized into two groups: the ST-segment elevation group (n = 27) and the depression group (n = 22). There were no differences in age, gender, or cardiovascular risk factors between the two groups. The distribution of the spastic site in the LAD was also similar. A total reduction in luminal diameter during a provoked attack was more often observed in the ST-segment elevation group than in the ST-segment depression group (37% vs 9%, p = 0.02). Collateral circulation to the LAD was found in only one patient in each group. There were no differences between the two groups in heart rate, systolic BP, and double product of heart rate and systolic BP during the attack. The incidence of acetylcholine-induced anginal attack with U-wave inversion in the ST-segment depression group was nearly as high as that in the ST-segment elevation group (77% vs 78%, p > 0.99). CONCLUSIONS: The development of transient U-wave inversion during vasospasm of the LAD induced by intracoronary injection of acetylcholine does not depend on the magnitude of myocardial ischemia as judged by the direction of ST-segment shift.