This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category T 1-2, node-negative, and no distant metastasis) treated with traditional elective neck ...dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points.
Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age ≥ 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with ≥ 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND.
Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively (
= .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9;
for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively (
for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group.
SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.
The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study ...elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.
Nanodiscs are phospholipid−protein complexes which are relevant to nascent high-density lipoprotein and are applicable as a drug carrier and a tool to immobilize membrane proteins. We evaluated the ...structure and dynamics of the nanoparticles consisting of dimyristoylphosphatidylcholine (DMPC) and apolipoprotein A-I (apoA-I) with small-angle neutron scattering (SANS) and fluorescence methods and compared them with static/dynamic properties for large unilamellar vesicles. SANS revealed that the nanodisc includes a lipid bilayer with a thickness of 44 Å and a radius of 37 Å, in which each lipid occupies a smaller area than the reported molecular area of DMPC in vesicles. Fluorescence measurements suggested that DMPC possesses a lower entropy in nanodiscs than in vesicles, because apoA-I molecules, which surround the bilayer, force closer lipid packing, but allow water penetration to the acyl chain ends. Time-resolved SANS experiments revealed that nanodiscs represent a 20-fold higher lipid transfer via an entropically favorable process. The results put forward a conjunction of static/dynamic properties of nanodiscs, where the entropic constraints are responsible for the accelerated desorption of lipids.
We report a rare case of myxofibrosarcoma arising in the neck. A 67-year-old man presented with a neck mass. Contrast-enhanced magnetic resonance imaging showed a roughly well-defined tumor with ...enhancement in the neck. It was difficult to distinguish whether it was benign or malignant by fine-needle aspiration cytology. The neck tumor was resected for the purpose of diagnostic treatment. The tumor was pathologically diagnosed as a low-grade myxofibrosarcoma with positive surgical margin. Furthermore, neck dissection was performed as additional treatment. However, the surgical margin was also pathologically positive. Therefore, postoperative radiation therapy with 60Gy was performed. The patient has remained alive for 76 months without recurrence after the first surgery. Myxofibrosarcoma has a high local recurrence rate in patients with positive pathological margin in surgery, but it may be possible to achieve local control by postoperative radiation therapy.
Discoidal high-density lipoprotein (HDL) particles are known to fractionalize into several discrete populations. Factors regulating their size are, however, less understood. To reveal the effect of ...lipid composition on their formation and characteristics, we prepared several reconstituted HDLs (rHDLs) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine (POPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and sphingomyelin at phospholipid to apolipoprotein A-I ratios of 100 and 25. When reconstitution was conducted at 37°C, the efficiency of rHDL formation from POPC was decreased as compared with that conducted at 4°C. Moreover, large rHDLs with a Stokes diameter of 9.6nm became dominant over small rHDL with a diameter of 7.9nm, which was distinctly observed at 4°C. The aminophospholipids POPS and POPE promoted the formation of small rHDLs at 37°C, but fluorescence experiments revealed that they did so in a different fashion: Fluorescence lifetime data suggested that the head group of POPS reduces hydrophobic hydration, especially in small rHDLs, suggesting that this lipid stabilizes the saddle-shaped bilayer structure in small rHDLs. Fluorescence lifetime and anisotropy data showed that incorporation of POPE increases acyl chain order and water penetration into the head group region in large rHDLs, suggesting that POPE destabilizes the planar bilayer structure. These results imply that these aminophospholipids contribute to the formation of small rHDLs under biological conditions.
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► HDLs were reconstituted with several lipids. ► Efficiency of small rHDL formation from POPC was decreased at 37°C than at 4°C. ► POPS stabilized the saddle-shaped bilayer structure in small rHDLs and promoted the small rHDL formation. ► POPE destabilizes the planar bilayer structure and promoted the small rHDL formation.
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Background: The objective of the study is to evaluate the non-Inferiority of survival, the superiority of postoperative disability, and the complication of the neck in neck ...dissections based on sentinel lymph node navigation in early oral cancer patients, compared with standard selective neck dissections. Methods: This study was a randomized, multicenter, non-inferiority trial at 16 institutions in Japan. Eligibility criteria included histologically confirmed squamous cell carcinoma in the oral cavity; clinical categories T1 and T2, N0M0 by UICC TNM classification 7th edition, clinical depth of invasion (DOI) of T1 was over 4mm (defined as late T1); previously untreated; age at least 18 years; and written informed consent. We randomly assigned patients (1:1) to receive either sentinel lymph node biopsy (SNB) or standard selective neck dissections (ND) with stratification of T category (lateT1 vs T2) and subsite (tongue vs others). The primary endpoint was 3-year overall survival with a non-inferiority margin of 12%. Sentinel nodes (SNs) were detected using radioisotope method and examined with multislice frozen section analysis intraoperatively, following HE and cytokeratin stain for a final postoperative diagnosis. Patients with positive SNs had neck dissections in a one-stage or back up procedure. Results: Between November 2011 and January 2016, 271 patients were enrolled and randomized to SNB group (134 patients) and ND group (137 patients) with a median follow-up of 37 months (IQR 36-39). Pathological positive nodal status was 34% (46/132) in SNB group and 26% (34/133) in ND group (Chi-Square p = 0.10). 3-year overall survival in SNB group was 89% (95%CI 82-93%), which was non-inferior to that in ND group (86%, 95%CI 79-91%). 3-year relapse-free survival was 80% (95%CI 72-86%) in SNB group and 81% (95%CI 73-87%) in ND group. Arm abduction of postoperative 1 and 3 months in ND group was disturbed significantly compared with SNB group. Conclusions: SNB navigated ND could replace elective ND without survival disadvantage and reduce postoperative disability of the neck in patients with early oral cancer. Clinical trial information: 000006510.
Nascent high-density lipoproteins (HDLs), which are also known as discoidal HDLs, are formed by the interaction of apolipoprotein A-I (apoA-I) with transmembrane ATP-binding cassette transporter A1 ...(ABCA1). However, the molecular mechanism governing disc formation is not fully understood. Here, we evaluated the thermodynamic and kinetic stability of disc formation from mixtures of 1-palmitoyl-2-oleoylphosphatidylcholine and apoA-I by quantifying the discs and vesicles produced. Sodium cholate dialysis experiments revealed that the discs are thermodynamically more stable than the vesicle/apoA-I mixture (Δ*G = −52 kJ/disc mol at 37.0 °C) because the decrease in enthalpy (Δ*H = −620 kJ/disc mol) exceeds the decrease in entropy (TΔ*S = −570 kJ/disc mol). Circular dichroism spectral measurements ascribed 68% of the decrease in enthalpy during disc formation to the formation of helices in apoA-I. Fluorescence measurements suggested that phospholipids enclosed in the discs are more closely packed than those in the vesicles so that they are entropically destabilized. To determine if the disc could be spontaneously produced from vesicles, we measured the decrease in the turbidity of vesicles in response to the addition of apoA-I. However, the rate of disc formation was very slow, suggesting that the large kinetic barrier against disc formation makes the vesicle/apoA-I mixtures metastable. These results raise the possibility that ABCA1 may act to lower the activation energy, thereby facilitating disc formation.
Early-stage oral or oropharyngeal carcinomas are often treated with surgical resection. Resulting wounds that are too large for primary closure can be covered with skin grafts or patches made from ...various biomaterials. Recently, polyglycolic acid sheets have been used for this purpose.
We treated six patients with large wounds resulting from the resection of oral or oropharyngeal squamous cell carcinoma by grafting polyglycolic acid sheet patches. All patients were initially treated at the National Cancer Center East Hospital from March 2010 through July 2012. After mucosal resection, the wounds were covered with polyglycolic acid sheet patches attached with fibrin glue. Oral intake was started 4 days after surgery.
Mucosal resection was the initial treatment in seven patients (five with oral squamous cell carcinoma and two with oropharyngeal squamous cell carcinoma). The polyglycolic acid sheet patches became detached in two patients (on the day of surgery and on postoperative day 6), who then required large doses of analgesics. A patient who underwent tooth extraction also required large doses of analgesics. The other four patients required only small doses of analgesics. One patient had bleeding at the surgical site. No adverse effects were caused by the polyglycolic acid sheet patch or by fibrin glue.
Our study has shown that grafting of a polyglycolic acid sheet patch is effective and provides good pain control for patients with large, open wounds after mucosal resection of oral or oropharyngeal squamous cell carcinoma. We plan to evaluate tissue contraction and oral intake after polyglycolic acid patch grafting.
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