[Characteristics of lymph node metastasis of right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma].

Objective: To understand the characteristics and influencing factors of lymph node metastasis of the right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma (ESCC), and to explore the reasonable range of lymph node dissection and the value of right recurrent laryngeal nerve lymph node dissection. Methods: The clinicopathological data with thoracic ESCC were retrospectively analyzed, and the characteristics of lymph node metastasis along the right recurrent laryngeal nerve and its influencing factors were explored. Results: Eighty out of 516 patients had lymph node metastasis along the right recurrent laryngeal nerve, the metastasis rate was 15.5%. Among 80 patients with lymph node metastasis along the right recurrent laryngeal nerve, 25 cases had isolated metastasis to the right recurrent laryngeal nerve lymph node but no other lymph nodes. The incidence of isolated metastasis to the recurrent laryngeal nerve lymph node was 4.8% (25/516). A total of 1 127 lymph nodes along the right recurrent laryngeal nerve were dissected, 115 lymph nodes had metastasis, and the degree of lymph node metastasis was 10.2%. T stage, degree of tumor differentiation and tumor location were associated with right paraglottic nerve lymph node metastasis (all P<0.05). The lymph node metastasis rate along the right recurrent laryngeal in patients with upper thoracic squamous cell carcinoma (23.4%, 26/111) was higher than that of patients with middle (13.5%, 40/296) and lower (12.8%, 14/109) thoracic squamous cell carcinoma (P=0.033). In patients with poorly differentiated ESCC (20.6%, 37/180) the metastasis rate was higher than that of patients with moderately (14.6%, 39/267) and well-differentiated (5.8%, 4/69; P<0.05). The lymph node metastasis rate of patients with stage T4 (27.3%, 3/11) was higher than that of patients with stage T1 (9.6%, 19/198), T2 (19.0%, 16/84) and T3 (18.8%, 42/1 223; P<0.05). Multivariate regression analysis showed that tumor location (OR=0.61, 95% CI: 0.41-0.90, P=0.013), invasion depth (OR=1.46, 95% CI: 1.11-1.92, P=0.007), and differentiation degree (OR=1.67, 95% CI: 1.13-2.49, P=0.011) were independent risk factors for lymph node metastasis along right recurrent laryngeal nerve of ESCC. Conclusions: The lymph node along the right recurrent laryngeal nerve has a higher rate of metastasis and should be routinely dissected in patients with ESCC. Tumor location, tumor invasion depth, and differentiation degree are risk factors for lymph node metastasis along right recurrent laryngeal nerve in patients with ESCC.

[The value and related complications of lymph node dissection along bilateral recurrent laryngeal nerves in esophageal cancer patients].

Esophageal cancer is one of the most common malignant tumors of digestive tract, lymph node metastasis is a frequently encountered metastasis in the esophageal cancer patients. The number of lymph node metastasis is reported as an important prognostic factor, and it also affects the choice of postoperative treatments in the esophageal cancer. It was reported that the recurrent laryngeal nerve lymph nodes are the most common sites of nodal metastasis and need to be completely dissected during the esophagectomy for thoracic esophageal cancers. Dissection of the lymph nodes along bilateral recurrent laryngeal nerves not only improves the accuracy of staging, but also improves postoperative survival of esophageal cancer patients due to reducing the local recurrence. However, it also brings problems such as injury of laryngeal recurrent nerves, and increases postoperative complications such as pulmonary complications and malnutrition due to aspiration and coughing. Therefore, it is necessary to preserve the structure and function of bilateral recurrent laryngeal nerves during esophagectomy through careful manipulations, and minimize the impact of complications in prognosis and quality of life from injury to the recurrent laryngeal nerve.

[Thoracic recurrent laryngeal nerve lymph node metastasis guides the cervical lymph node dissection of patients with esophageal cancer].

Three-field lymph node dissection improved the postoperative survival and accuracy of pathological staging of patients with esophageal cancer, and reduced the postoperative local recurrence rate of esophageal cancer patients. However, this surgical procedure enlarged the trauma, cansed more complications, prolonged postoperative hospital stays, and seriously impaired the postoperative adjuvant therapy. Therefore, selection of patients who are suitable for three-field lymph node dissection is extremely important. The special anatomical location of recurrent laryngeal nerve lymph nodes is potentially suitable for it to serve as sentinel lymph node for the evacuation of cervical lymph nodes dissection in esophageal cancer. The guiding value of recurrent laryngeal nerve lymph node metastasis in cervical lymph node dissection of thoracic esophageal cancer is reviewed.

[Current status of prognostic evaluation of esophageal cancer patients by circumferential resection margin].

Esophageal cancer is the sixth leading cause of cancer-related death worldwide due to its high malignancy and poor prognosis. In recent decades, the applications of new technologies, devices and neoadjuvant therapy lead to the great progress in the diagnosis and treatment of esophageal cancer. However, the five-year survival rate of esophageal cancer remains unsatisfied. Clinical and pathological factors such as the primary tumor (T), regional lymph nodes (N) and distant metastasis (M) and the longitudinal margins of esophageal lesions, lymphatic invasion, peripheral nerve invasion have been identified as important predictors of the prognosis of esophageal cancer. However, the effect of circumferential resection margin on the prognosis evaluation of esophageal cancer is still controversial, and no definite identification of circumferential resection margin of esophageal cancer has been acknowledged worldwide. Therefore, the studies of circumferential resection margin involvement in predicting the prognosis of esophageal cancer are reviewed.

[Key technology of lymph node dissection along recurrent laryngeal nerve and its associated complication prevention in patients with thoracic esophageal cancer].

Esophageal cancer is one of the most prevalent cancers in China. Lymph node metastasis is one of the most important prognostic factors and severely affect the long-term survival after surgical treatment. Therefore, systemic two-field lymph node dissection including thoracic and abdominal draining nodes of the esophagus during surgery is essential in order to improve the long-term survival for the patients with thoracic esophageal cancer, and it is also the basis for precise staging and postoperative adjuvant treatment regimen- making. As reported in the literature, lymph node metastases along bilateral recurrent laryngeal nerve was the highest, therefore, the lymph node dissection along bilateral recurrent laryngeal nerve is the most important manipulation during esophagectomies, however, it is also the most technically difficult procedure during operation. It usually results in postoperative complications especially the respiratory complications due to paralysis of recurrent laryngeal nerves caused by lymph node dissection. Therefore, the gain and loss of lymph node dissection along bilateral recurrent laryngeal nerve has been a disputed and entangle topic for thoracic surgeons, and the purpose of this paper is to summarize author's experience and the key technology to prevent the associated complications in lymph node dissection along recurrent laryngeal nerve during esophagectomies for the patients with thoracic esophageal cancer.

Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation.

To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing-finishing pigs by i.v. administration at a single dose of 10 mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C(i,v) = X(0 )(8.4191 × 10(-4) × e(-0.2371t) + 1.2788 × 10(-5) × e(-0.0069t)) after i.v. and C(p.o) = X(0) (-8.4964 × 10(-4) × e(-0.5840t) + 8.4195 × e(-0.2371t) + 7.6869 × 10(-6) × e(-0.0069t)) after p.o. Monte Carlo simulation showed that T(>MIC) was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance.

A physiologically based pharmacokinetic model for valnemulin in rats and extrapolation to pigs.

A flow-limited, physiologically based pharmacokinetic (PBPK) model for predicting the plasma and tissue concentrations of valnemulin after a single oral administration to rats was developed, and then the data were extrapolated to pigs so as to predict withdrawal interval in edible tissues. Blood/tissue pharmacokinetic data and blood/tissue partition coefficients for valnemulin in rats and pigs were collected experimentally. Absorption, distribution and elimination of the drug were characterized by a set of mass-balance equations. Model simulations were achieved using a commercially available software program. The rat PBPK model better predicted plasma and tissue concentrations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, lung and muscle were 0.96, 0.94, 0.96, 0.91 and 0.91, respectively. The rat model parameters were extrapolated to pigs to estimate valnemulin residue withdrawal interval in edible tissues. Correlation (R(2) ) between predicted and observed liver, kidney and muscle were 0.95, 0.97 and 0.99, respectively. Based on liver tissue residue profiles, the pig model estimated a withdrawal interval of 10 h under a multiple oral dosing schedule (5.0 mg/kg, twice daily for 7.5 days). PBPK models, such as this one, provide evidence of the usefulness in interspecies PK data extrapolation over a range of dosing scenarios and can be used to predict withdrawal interval in pigs.

Pharmacokinetics and bioavailability of valnemulin in broiler chickens.

The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic characterization was performed by non-compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(V(z)) of 4.27 ± 0.99 L /kg. Mean valnemulin t(1/2ß)(h), Cl(ß)(L /h /kg), V(ss)(L /kg) and AUC((0-∞))(µg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a C(max) of 2.2 µg/mL achieved at 0.43 h (t(max)), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 µg/mL, 1.54 ± 0.27 h and 74.42%. A multiple-peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2-6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens.

A fast automatic RBS/w channeling system for damage depth profiling.

A computer-aided data acquisition coupling with goniometer-control system dedicated for damage depth profile measurements is established. The channeling direction searching is performed along tilt and azimuth directions. The system includes a computer code to convert the measured spectra into damage depth profile. The analyzing time for each sample requires approximately 20-30 min. The damage depth profiles of the self-implanted (100) silicon samples are in reasonable agreement with the calculated results yielded by the SRIM Monte-Carlo simulation code.