Selective Neck Dissection and Survival in Pathologically Node-Positive Oral Squamous Cell Carcinoma.

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is neck metastasis, which is treated by neck dissection. Although selective neck dissection (SND) is a useful tool for clinically node-negative OSCC, its efficacy for neck node-positive OSCC has not been established. Sixty-eight OSCC patients with pN1⁻3 disease who were treated with curative surgery using SND and/or modified-radical/radical neck dissection (MRND/RND) were retrospectively reviewed. The neck control rate was 94% for pN1⁻3 patients who underwent SND. The five-year overall survival (OS) and disease-specific survival (DSS) in pN1-3 OSCC patients were 62% and 71%, respectively. The multivariate analysis of clinical and pathological variables identified the number of positive nodes as an independent predictor of SND outcome (OS, hazard ratio (HR) = 4.98, 95% confidence interval (CI): 1.48⁻16.72, p < 0.01; DSS, HR = 6.44, 95% CI: 1.76⁻23.50, p < 0.01). The results of this retrospective study showed that only SND for neck node-positive OSCC was appropriate for those with up to 2 lymph nodes that had a largest diameter ≤3 cm without extranodal extension (ENE) of the neck and adjuvant radiotherapy. However, the availability of postoperative therapeutic options for high-risk OSCC, including ENE and/or multiple positive lymph nodes, needs to be further investigated.

Tumor-infiltrating CD8+ T-cell density is an independent prognostic marker for oral squamous cell carcinoma.

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear in oral squamous cell carcinoma (OSCC). METHODS: We evaluated the associations between tumor-infiltrating CD8+ T-cell density and survival in five distinct compartments in 139 OSCC cases. RESULTS: There was a significant association between increased tumor-infiltrating CD8+ T cells and their distribution. High parenchymal CD8+ T-cell density at the invading tumor edge was associated with improved overall survival (OS) and disease-specific survival (DSS; P < 0.01 and P < 0.01, respectively). High stromal CD8+ T-cell density at the tumor periphery was also associated with improved recurrence-free survival (RFS; P < 0.01). Cox regression analysis revealed that high stromal CD8+ T-cell density at the tumor periphery and high parenchymal CD8+ T-cell density at the invading edge were independent prognostic makers (hazard ratio: 0.38 and 0.19, 95% confidence interval, 0.18-0.80 and 0.05-0.72, P = 0.01 and 0.01, respectively) for RFS and OS, respectively. CONCLUSIONS: Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis.

Quantitative Evaluation of Cephalometric Radiographs of Patients With Hemifacial Microsomia.

OBJECTIVE: To clarify the morphological characteristics of hemifacial microsomia (HFM) by quantitative analysis of cephalometric radiographs. DESIGN: Retrospective study of imaging data. SETTING: Imaging data were obtained from the records of Sapporo Medical University Hospital. PATIENTS: A total of 183 patients with HFM. MAIN OUTCOME MEASURES: We used linear and angular measurements and analyzed the middle face and lower face. RESULTS: The ratios of the affected side to the unaffected (A/U) side of the lateral distance of the mandibular condyle, the mandibular ramus height, and the length of the body of the mandible in the HFM group were significantly lower than in the control group. The inclination of the body of the mandible was significantly larger in the side with HFM than in the unaffected side, and the extent of the mandibular ramus was significantly lower than in the unaffected side. The A/U ratios of the extent of the angle of the mandible and the inclination of the body of the mandible in the HFM group were larger than in the control group. Moreover, the length and the inclination of the body of the mandible had significant correlations with the distance of the shift of the menton. CONCLUSIONS: It is suggested that improving the hypoplasia of the length of the body of the mandible and the extent of the angle of the mandible on the affected side will lead to more effective treatment of jaw deformity in patients with HFM.

Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1.

Recent studies have shown that long noncoding RNAs (lncRNAs) have pivotal roles in human malignancies, although their significance in oral squamous cell carcinoma (OSCC) is not fully understood. In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC), we identified 15 lncRNAs aberrantly expressed in cancer tissues. We then validated their expression in 18 OSCC cell lines using qRT-PCR and identified 6 lncRNAs frequently overexpressed in OSCC. Among those, we found that knocking down DLEU1 (deleted in lymphocytic leukemia 1) strongly suppressed OSCC cell proliferation. DLEU1 knockdown also suppressed migration, invasion, and xenograft formation by OSCC cells, which is suggestive of its oncogenic functionality. Microarray analysis revealed that DLEU1 knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44, and TP63, suggesting that DLEU1 regulates HA-CD44 signaling. Expression of DLEU1 was elevated in 71% of primary OSCC tissues, and high DLEU1 expression was associated with shorter overall survival of HNSCC patients. These data suggest that elevated DLEU1 expression contributes to OSCC development, and that DLEU1 may be a useful therapeutic target in OSCC.

Tumor budding is an independent prognostic marker in early stage oral squamous cell carcinoma: With special reference to the mode of invasion and worst pattern of invasion.

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p<0.01) and tumor budding (p<0.01) were associated with regional metastasis as well as lymphovascular invasion (p = 0.04) in univariate analysis. In logistic regression analysis, however, tumor budding was the only independent predictor of regional metastasis (hazard ratio (HR) = 3.05, 95% confidence interval (CI) = 0.29-5.30, p<0.01). All three invasive patterns, the mode of invasion, WPOI, and tumor budding, were found to be significant predictors of 5-year disease-free survival (p<0.01, p = 0.03, and p<0.01, respectively) as well as lymphovascular invasion (p = 0.02) and perineural invasion (p = 0.02). A final model for Cox multivariate analysis identified the prognostic advantage of the intensity of tumor budding (HR = 2.19, 95% CI = 1.51-3.18, p<0.01) compared with the mode of invasion and WPOI in disease-free survival. Our results indicate that the intensity of tumor budding may be a novel diagnostic biomarker, as well as a therapeutic tool, for regional metastasis in patients with cT1,2N0M0 OSCC. If the pancytokeratin-based immunohistochemical features of more than five buds, and a grade 4C or 4D mode of invasion are identified, careful wait-and-see follow-up in a short period with the use of imaging modalities is desirable. If there are more than ten buds, a grade 4D mode of invasion, or WPOI-5 in the same section, wide resection of the primary tumor with elective neck dissection should be recommended.

Relationship Between Mandibular Ramus Height and Masticatory Muscle Function in Patients With Unilateral Hemifacial Microsomia.

OBJECTIVE: To clarify the relationship between mandibular ramus height and function of masticatory muscles in patients with hemifacial microsomia. DESIGN: Retrospective study of imaging and physiological data. SETTING: Images and physiological data were obtained from the records of Sapporo Medical University Hospital. PATIENTS: A total of 29 patients with hemifacial microsomia who showed Pruzansky grades I, II deformity. MAIN OUTCOME MEASURES: Mandibular ramus height and masticatory muscle volume were evaluated with multi-detector row computed tomography. The electromyographic value was measured by the K7 Evaluation System. The hemifacial microsomia patients were classified into three groups based on the mandibular ramus height ratio of the affected and unaffected sides: group 0, >1.00; group 1, 1.00 to 0.85; group 2, <0.85. The Tukey-Kramer method and Games-Howell method were used to determine correlations between parameters. RESULTS: Decreased mandibular ramus height was significantly correlated with both reduced electromyographic values of the masseter muscle (P < .05) and the amount of mandibular lateral deviation at the time of maximum opening (P < .05) on the affected side. These differences were prominent in unilateral hemifacial microsomia patients classified as group 2. CONCLUSIONS: Decreased mandibular ramus height may cause dysfunction of the masseter muscles but not the temporal muscle on the affected side in patients with hemifacial microsomia.

Hypoxia-induced epithelial-mesenchymal transition is regulated by phosphorylation of GSK3-ß via PI3 K/Akt signaling in oral squamous cell carcinoma.

OBJECTIVE: Epithelial-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis induced by hypoxia. Here, we examined whether phosphorylation of GSK3-ß via phosphoinositide 3-kinase (PI3 K)/Akt signaling is involved in enhancing the hypoxia-induced EMT in oral squamous cell carcinoma (OSCC). STUDY DESIGN: Experiments were performed in OSCC cell lines (HSC-2, HSC-3, HSC-4, SAS, and HO-1-U-1) under normoxic or hypoxic conditions. The EMT was assessed by Matrigel invasion assays and wound healing assays. OSCC cell lines (HSC-2 and HSC-4) overexpressing hypoxia-inducible factor (HIF)-1α were established to examine the effects of HIF-1α on EMT-related factors. Immunohistochemical staining was performed to examine phosphorylation of GSK3-ß in 33 cases of tongue squamous cell carcinoma. RESULTS: Under hypoxic conditions, OSCC cell lines exhibited HIF-1α expression and showed evidence of the EMT. In cells overexpressing HIF-1α, the levels of phospho-Akt and phospho-GSK3-ß were increased, resulting in induction of the EMT. Inhibition of GSK3-ß phosphorylation suppressed these effects. Moreover, the intensity of pGSK3-ß staining was significantly increased with cN stage and cTNM stage in patients with tongue squamous cell carcinoma. CONCLUSIONS: Our data showed that the hypoxia-induced EMT in OSCC was enhanced by GSK3-ß phosphorylation, suggesting that GSK3-ß may be important in the invasion and metastasis of OSCC.

TIMP-1 as well as Microvessel Invasion and High Nuclear Grade Is a Significant Determinant Factor for Extension of Tumor Diameter in Localized RCC.

Objectives. To clarify what kind of pathological factor is necessary for the extension of tumor diameter in localized RCC, we studied localized RCC patients. Methods. We retrospectively reviewed medical records of 237 RCC patients in our institute who underwent nephrectomy. We performed immune histological analysis of MMP-2, MMP-9, TIMP-1, TIMP-2, and MT-MMP-1 for all samples. Results. Among the clinicopathological factors, multivariate analysis revealed nuclear grade; TIMP-2 and MT-MMP-1 were independent prognostic factors of localized RCC (risk ratio 1.50, p = 0.037, risk ratio 1.12, p = 0.008, and risk ratio 1.84, p = 0.045, resp.). By the multiple logistic regression analysis among pT1a versus pT1b, TIMP-1 was an independent factor (risk ratio 3.30, p = 0.010) whereas all pT1 versus pT2a and all pT1 + pT2a versus pT2b high nuclear grade (risk ratio 5.15, p = 0.0015) and Micro vessel invasion (MVI, risk ratio 3.08, p = 0.002) were independent factors. For all pT1 + pT2a versus pT2b, nuclear grade (risk ratio 3.39, p = 0.020) and MVI (risk ratio 2.91, p = 0.018) were independent factors. Conclusion. Higher expression of TIMP-1 is necessary for advancement tumor diameter from pT1a to pT1b, and a process of tumor diameter extension beyond pT1 and pT2a category needs presence of MVI and high nuclear grade.

Efficacy of transurethral prostate enucleation by bipolar system for patients with benign prostatic hyperplasia.

BACKGROUND: The aim of this paper was to evaluate the efficacies and safety of transurethral prostate enucleation by bipolar system (TUEB) for the patients with benign prostatic hyperplasia (BPH). METHODS: We prospectively evaluated clinical outcomes of TUEB in 55 patients with BPH from July 2005 to January 2011. Mean ages of the patients were 69.2 years. International Prostate Symptom Score (IPSS), IPSS-quality of life (IPSS-QOL) were assessed before and 12 months after surgery. Serum PSA, maximal flow rate (MFR), and post-void residual (PVR) were also evaluated before and 6 and 12 months after surgery. RESULTS: The median prostate volumes and resection volumes were 64.1 g (interquartile range [IQR]: 48-87) and 34.4 g (25-60.2), respectively. The median operation time was 138.0 min (100.2-169.2). Total IPSS scores and IPSS-QOL were significantly improved (from 24 [17-31] to 5 [2-8] points, and from 6 [5-6] to 2 [1-2] points, both P<0.001). MFR and PVR were significantly improved 6 and 12 months after TUEB (from 6.2 [3.9-8.3] to 15.1 [10.5-20.9], and 14.6 [10.2-20.5] mL/s, P<0.0001, and from 151.5 [81.5-284.7] to 16.5 [0-30.5], and 6.0 [0-41.0] mL, P<0.0001, respectively). Serum PSA also significantly decreased, 6 and 12 months (from 7.5 [4.7-9.8] to 1.1 [0.5-1.5], and 0.6 [0.3-1.9] ng/mL, P<0.0001). Although hemoglobin decreased after operation, no case experienced blood transfusion. Three episodes of urinary tract infections, 14 cases of mild stress urinary incontinence, 2 cases of urinary retention were occurred transiently with recovery within 1 month after surgery. CONCLUSIONS: We identified favorable efficacy and safety of TUEB. TUEB appears to be another possibility in the treatment of BPH.

Laparoscopic adrenalectomy for adrenal tumors: a 21-year single-institution experience.

OBJECTIVE: We have performed laparoscopic adrenalectomy including retroperitoneoscopic adrenalectomy via a single large port (RASLP) and conventional laparoscopic adrenalectomy (CLA) for adrenal tumors since 1992, and report our experience to date. METHODS: The study population consisted of 134 patients who underwent laparoscopic adrenalectomy from 1992 to 2012. Fifty-eight patients (18 aldosterone-producing adenomas, 13 adenomas with Cushing's syndrome, 1 adenoma with preclinical Cushing's syndrome, and 26 nonfunctioning tumors) were treated using RASLP, and 76 patients (33 aldosterone-producing adenomas, 17 adenomas with Cushing's syndrome, 6 adenomas with preclinical Cushing's syndrome, 17 pheochromocytomas, and 3 nonfunctioning tumors) were treated using CLA. Complications were graded according to the modified Clavien system. RESULTS: The majority of RASLPs were performed during the 1990s, whereas all patients underwent CLA after 2000. The mean operation times (166 vs. 205 minutes, p < 0.01) and intraoperative estimated blood loss (85 vs. 247 mL, p < 0.01) were significantly lower in the CLA group. Conversion to open surgery was required in three patients (5%) in the RASLP group and five patients (7%) in the CLA group (p = 0.73). Postoperative complications were grade 1 in three patients and grades 4 and 5 in one patient each in the RASLP group, whereas grade 2 in one patient was observed in the CLA group (p = 0.085). CONCLUSION: Although this study included biases such as different eras and indications, CLA resulted in decreased operative times, blood loss, and postoperative complications compared with RASLP. CLA has so far become our preferred procedure for patients with adrenal tumor in our experience.

Lower urinary tract symptoms in female patients with pelvic organ prolapse: efficacy of pelvic floor reconstruction.

OBJECTIVE: To evaluate the impact of pelvic floor reconstruction on lower urinary tract symptoms in patients with pelvic organ prolapse. METHODS: We carried out a prospective study at a single institution. A total of 223 female patients who underwent tension-free vaginal mesh surgery for pelvic organ prolapse between January 2006 and February 2010 were enrolled and prospectively evaluated. A total of 171 cases with concurrent stress urinary incontinence (76% of all cases) underwent concomitant transobturator tape sling. For evaluation of lower urinary tract symptoms, parameters included International Prostate Symptom Score, its quality of life score, International Consultation on Incontinence Questionnaires Short Form, overactive bladder questionnaire, maximal flow rate and postvoid residual. These parameters were evaluated at baseline, and at 3, 6 and 12 months after the surgery. RESULTS: The severity of International Prostate Symptom Score total scores significantly correlated with preoperative pelvic organ prolapse quantification stages, overactive bladder questionnaire total scores and International Consultation on Incontinence Questionnaires Short Form scores. A total of 37% of stage 4 showed ≥20 International Prostate Symptom Score (severe cases). Postvoid residual significantly increased in stage 4 compared with stage 2. Tension-free vaginal mesh improved International Prostate Symptom Score, overactive bladder questionnaire and International Consultation on Incontinence Questionnaires Short Form significantly, and also achieved grade 0 pelvic organ prolapse quantification in 91% of all cases at 1 year after surgery. Postvoid residual values significantly improved and remained stable for 1 year. Worse overactive bladder questionnaire score was a significant predictive factor for poor postoperative International Prostate Symptom Score. CONCLUSION: The tension-free vaginal mesh plus transobturator tape procedure improves lower urinary tract symptoms in the majority of patients presenting pelvic organ prolapse.

Anti carbocyanative cyclization of enynes under nickel catalysis.

Anti carbocyanative cyclization using 1,6-enynes under nickel catalysis is described. This reaction is triggered by hydronickelation to alkenes followed by carbometalation. Steric repulsion caused by the bulky substituents on alkynes promotes isomerization of the carbon-carbon double bond geometry in an organonickel intermediate to introduce both alkyl and cyano groups in an anti fashion.

Clinical significance of computed tomographic assessment and anatomic features of the inferior alveolar canal as risk factors for injury of the inferior alveolar nerve at third molar surgery.

PURPOSE: To assess the clinical features of the inferior alveolar canal (IAC) using computed tomography (CT) and to analyze the significance of CT examination at third molar surgery. MATERIALS AND METHODS: A retrospective cohort study was performed involving 99 patients (145 teeth). The relationship between cortication status, buccolingual position, and shape of the IAC on the CT image and inferior alveolar nerve (IAN) injury after third molar surgery were statistically analyzed. RESULTS: The shape of the IAC was categorized into 3 groups: round/oval, teardrop, and dumbbell. IAN injury was observed in 7 of 145 cases (4.8%). All 7 cases exhibited absence of cortication; 3 were dumbbell shape and 4 were round/oval. According to logistic regression analysis of cases with absence of cortication, IAC shape was closely related to IAN injury. CONCLUSIONS: These results suggest that assessment of the IAC shape and cortication status at third molar surgery may be clinically useful.

Stereoselective synthesis of vinyl-substituted (Z)-stilbenes by rhodium-catalysed addition of arylboronic acids to allenic alcohols.

Vinyl-substituted (Z)-stilbenes are stereoselectively synthesised on treatment of 4-arylbuta-2,3-dien-1-ols with arylboronic acids in the presence of a rhodium(i) catalyst. The reaction proceeds through the regioselective addition of organorhodium(i) species across the aryl-substituted carbon-carbon double bond of the allene moiety and subsequent delta-elimination of Rh(i)-OH.

[Clinical investigation of bisphosphonate-related osteonecrosis of the jaws].

We examined the clinical features of bisphosphonate(BP)-related osteonecrosis of the jaws(BRONJ), a serious complication resulting from intravenous BP treatment for multiple myeloma and malignant tumors with bone metastasis. We retrospectively reviewed the medical records of 36 patients who received intravenous BP therapy for the above-mentioned conditions, at Sapporo Medical University Hospital between July 2006 and October 2008. BP therapy caused BRONJ in 7 of 24 patients, but did not affect the bones of the other 17 patients. The other 12 of the 36 patients involved in the study were prescribed BP only after they had undergone an oral examination and treatment for dental inflammation. Of these patients, 7 developed BRONJ with BP treatment, after tooth extraction or acute dental inflammation. Treating dental inflammation before prescribing BP prevented the development of BRONJ. BRONJ is highly intractable and does not resolve with the standard treatment for osteomyelitis. Therefore, preventive therapy, which can be achieved by cooperation between medical doctors and dentists, is currently the most effective strategy for BRONJ. Conservative treatment with antibiotics may also be useful for maintaining or improving the quality of life of BRONJ patients.

A case of retroperitoneal bronchogenic cyst treated by laparoscopic surgery.

We describe herein a rare case of a retroperitoneal bronchogenic cyst successfully treated by laparoscopic surgery. A 39-year-old man with low-grade fever was referred to our hospital because of suspicion of an adrenal tumor. Abdominal computerized tomography (CT) and ultrasonography revealed a homogenous solid mass, 35 x 30 mm in diameter, in the left suprarenal region. Laboratory studies showed that the levels of adrenal hormones were normal except for the white blood cell count of 9,700/microL and C-reactive protein of 1.7 mg/dl. We diagnosed it as a non-functioning adrenocortical adenoma or an adrenal cyst. However, one year later he underwent laparoscopic surgery because the mass had gradually increased by 10 mm and the low-grade fever persisted. Pathological evaluation of the surgical specimens established the diagnosis of retroperitoneal bronchogenic cyst. The low-grade fever disappeared after the surgery.

[Enucleation of renal cell carcinoma in von Hippel-Lindau disease using a microwave tissue coagulator].

The patient was a 37-year-old man who had undergone left nephrectomy under the diagnosis of left renal cell carcinoma associated with von Hippel-Lindau (VHL) disease 4 years ago. Computed tomography (CT) revealed 3 individual tumors 20 mm, 13 mm and 9 mm in maximum diameter in the right kidney. All three renal tumors were enucleated with a microwave tissue coagulator (MTC) without renal pedicle clamping. There were no major complications related to nephron-sparing surgery such as postoperative bleeding, persistent urine leakage and deterioration of renal function. Our findings suggest that renal tumors with VHL disease can be enucleated using a MTC safely and successfully without damaging renal function.