Impact of routine recurrent laryngeal nerve monitoring in prone esophagectomy with mediastinal lymph node dissection.

BACKGROUND: The problem of recurrent laryngeal nerve (RLN) paralysis (RLNP) after radical esophagectomy remains unresolved. Several studies have confirmed that intraoperative nerve monitoring (IONM) of the RLN during thyroid surgery substantially decreases the incidence of RLN damage. This study tried to determine the feasibility and effectiveness of IONM of the RLN during thoracoscopic esophagectomy in the prone position for esophageal cancer. METHODS: All 108 patients who underwent prone esophagectomy at Tohoku University Hospital between July 2012 and March 2015 were included in this study. We divided patients into two groups: a control group (No-Monitoring group, surgery without IONM; n = 54) and a study group (Monitoring group, surgery with IONM; n = 54). In Monitoring group, neural stimulation was performed for both RLNs before and after dissection in the thoracic procedure, then for RLNs and vagus nerves (VNs) in the cervical procedure. The feasibility of IONM in Monitoring group and early surgical outcomes were retrospectively compared with those in No-Monitoring group. RESULTS: IONM could be performed for 47 cases (87.0%) in Monitoring group. Reasons for discontinuation were use of muscle relaxants (3 patients), change in thoracotomy procedure (2 patients), past rib bone fracture (1 patient), and allergic shock by transfusion (1 patient). Right RLNPs were identified postoperatively in 4 patients, and left RLNPs in 23 patients. IONM sensitivities were 92.7 and 88.0% for the right and left VNs, respectively. Incidences of postoperative RLNP, aspiration, and primary pneumonia did not differ significantly between groups. CONCLUSIONS: This study confirmed the feasibility and safety of IONM of the RLN for thoracoscopic esophagectomy in the prone position. No significant differences in postoperative outcomes were seen between esophagectomy with and without IONM.

Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has recently become one of the most effective therapies for the treatment of esophageal squamous cell carcinoma (ESCC). However, it is also true this treatment has not been effective in all patients. Therefore, it is very important to evaluate the surrogate marker of dCRT in order to improve clinical outcomes of patients with ESCC. On the other hand, our previous study had suggested that murine double minute 2 (MDM2) and p16 were associated with chemoradioresistance in ESCC. METHODS: We selected pretreatment biopsy specimens of ESCC patients from our prospective clinical study on dCRT. Seventy-nine cases histologically diagnosed as ESCC were used. We immunohistochemically investigated these specimens using antibodies against MDM2, p53, p16, and Ki-67. RESULTS: The patients included 68 males and 11 females with a mean age of 63.3 years. The number of patients in each clinical stage was as follows: 22 in c-Stage I; 17 in c-Stage II; and 40 in c-Stage III. cT, cN, and cStage were significantly more advanced in the Failure group (including patients with persistent and recurrent disease after dCRT) than in the complete response (CR) group (patients with persistent CR after dCRT). The clinical stage inversely correlated with the CR rate and the rescue rate after failure. The overall survival rate was significantly worse in the patients with advanced cT, cN, and cStage levels, and in the Failure group. MDM2 positivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.014). The number of patients with an absence of p16 immunoreactivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.010) but not in cStageI or cStageII. Moreover, the overall survival with a Ki-67 ≥ 33.7% was significantly better than that with <33.7% for patients in cStageIII (P = 0.024). CONCLUSIONS: The results of this study suggested that MDM2 and p16 are predictive markers for chemoradioresistance in cStageIII ESCC and Ki-67 is a prognostic marker following dCRT in cStageIII ESCC. These issues could contribute to the formulation of treatment strategy for patients with advanced ESCC.

Comparison of short-term outcomes between prone and lateral decubitus positions for thoracoscopic esophagectomy.

BACKGROUND: Prone thoracoscopic esophagectomy was introduced at our institution from 2012. This study describes our experiences of the main differences between thoracoscopic esophagectomy in the prone and traditional left lateral decubitus positions together with an analysis of the short-term surgical outcomes. METHOD: In total, 87 patients undergoing thoracoscopic esophagectomy between January 2012 and October 2013 at Tohoku University Hospital were enrolled; of these, 54 and 33 patients were operated in the prone (Group P) and lateral decubitus (Group L) positions, respectively. RESULTS: The background of the patients was similar, and there was no in-hospital mortality. There were no significant differences between the groups in terms of whole surgical duration, thoracic duration, and number of dissected lymph nodes. Total blood loss and thoracic estimated blood loss were significantly lower in Group P than Group L. Furthermore, postoperative pulmonary complications, intensive care unit stay, and hospital stay were significantly lower in Group P. CONCLUSION: Thoracoscopic esophagectomy in the prone position is feasible and safe. The prone position technique may be superior to conventional lateral decubitus position esophagectomy.

Complications following recurrent laryngeal nerve lymph node dissection in oesophageal cancer surgery.

OBJECTIVES: The recurrent laryngeal nerve lymph node is one of the most common metastatic sites in oesophageal cancer, and dissection of this lymph node is considered beneficial. Although the risk of complications from this procedure, such as recurrent laryngeal nerve palsy, is well known, few reports have detailed those risks in a large number of cases. Our study examined the risks of recurrent laryngeal nerve lymph node dissection, with a special focus on recurrent laryngeal nerve palsy. METHODS: Retrospectively collected data from 661 patients, who underwent transthoracic oesophagectomy for oesophageal cancer, were analysed. RESULTS: Recurrent laryngeal nerve palsy occurred in 36% of the patients. Among these patients, except those in whom recurrent laryngeal nerve was intentionally excised due to metastatic lymph node, permanent palsy was detected in 12%. Bilateral recurrent laryngeal nerve lymph node dissection, cervical anastomosis and upper oesophageal cancer were independent risk factors for recurrent laryngeal nerve palsy. Although recurrent laryngeal nerve palsy was a risk factor for aspiration, tracheostomy and postoperative pneumonia, it did not directly correlate with death caused by pneumonia. Among postoperative complications, only recurrent laryngeal nerve palsy correlated with bilateral recurrent laryngeal nerve lymph node dissection. CONCLUSIONS: Recurrent laryngeal nerve palsy is a complication that should be avoided but does not seem to be severe enough to affect patient survival after surgery. Although bilateral recurrent laryngeal nerve lymph node dissection can induce recurrent laryngeal nerve palsy in patients who undergo transthoracic oesophagectomy, this procedure did not correlate with aspiration and pneumonia.

A strategy for supraclavicular lymph node dissection using recurrent laryngeal nerve lymph node status in thoracic esophageal squamous cell carcinoma.

BACKGROUND: The desirability of supraclavicular lymph node (LN) dissection, which is the cervical part of three-field LN dissection, has been discussed for a long time. In this study, we examine the pattern of supraclavicular LN metastasis in esophageal cancer, with a particular focus on the correlation between recurrent laryngeal nerve (RLN) LN and supraclavicular LN metastasis. METHODS: In all, 220 cases of R0 resected T1 to T3 squamous cell carcinomas were retrospectively examined. All of these patients underwent bilateral RLN LNs dissection; none received cancer treatment before surgery. RESULTS: Of 21 upper esophageal cancer cases, 33.3% of the patients had metastasis in the supraclavicular LN. Every patient in whom supraclavicular LN metastasis developed had metastasis in the RLN LN. Of 141 cases of middle esophageal cancer, 19.1% had metastasis in the supraclavicular LN. Among the patients whose RLN LN metastasized, 38.3% had metastasis in the supraclavicular LN. A similar correlation between RLN LN and supraclavicular LN metastasis was observed in lower esophageal cancer cases, especially in T3 cases. When considering cancers of the esophagus and patients who had metastasis in the supraclavicular LN, our data demonstrated that RLN LN metastasis did not always lead to metastasis on the same side of the supraclavicular LN. CONCLUSIONS: The status of the RLN LN can be an indicator of supraclavicular LN dissection in upper esophageal cancer patients and advanced cases of middle and lower esophageal cancer patients. Bilateral supraclavicular LN dissection should be recommended even when only unilateral RLN LN metastasis occurs.

Murine double minute 2 and its association with chemoradioresistance of esophageal squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has been established as the standard treatment for esophageal squamous cell carcinoma (ESCC). However, many patients develop persistent or recurrent disease following dCRT. We investigated factors related to chemoradioresistance and treatment outcomes in patients with ESCC who underwent salvage esophagectomy after dCRT. PATIENTS AND METHODS: We selected 38 patients with persistent disease and 24 with recurrent disease who underwent salvage esophagectomy after dCRT, immunolocalized p53, p16, p27, murine double minute 2 (MDM2), cyclin D1, Ki-67, and epidermal growth factor receptor, and correlated the findings with clinicopathological features. RESULTS: MDM2 positivity was significantly higher among patients with persistent disease than among those with recurrent disease (p<0.0001). In addition, negative p16 expression was a predictor of poor prognosis among patients with persistent disease. CONCLUSION: MDM2 overexpression plays an important role in chemoradioresistance of ESCC; furthermore, negative p16 expression can predict poor prognosis of patients with persistent disease.

Subspace-based support vector machines for pattern classification.

In this paper, we discuss subspace-based support vector machines (SS-SVMs), in which an input vector is classified into the class with the maximum similarity. Namely, for each class we define the weighted similarity measure using the vectors called dictionaries that represent the class, and optimize the weights so that the margin between classes is maximized. Because the similarity measure is defined for each class, for a data sample the similarity measure to which the data sample belongs needs to be the largest among all the similarity measures. Introducing slack variables, we define these constraints either by equality constraints or inequality constraints. As a result we obtain subspace-based least squares SVMs (SSLS-SVMs) and subspace-based linear programming SVMs (SSLP-SVMs). To speedup training of SSLS-SVMs, which are similar to LS-SVMs by all-at-once formulation, we also propose SSLS-SVMs by one-against-all formulation, which optimize each similarity measure separately. Using two-class problems, we clarify the difference of SSLS-SVMs and SSLP-SVMs and evaluate the effectiveness of the proposed methods over the conventional methods with equal weights and with weights equal to eigenvalues.

Incremental learning of feature space and classifier for face recognition.

We have proposed a new approach to pattern recognition in which not only a classifier but also a feature space of input variables is learned incrementally. In this paper, an extended version of Incremental Principal Component Analysis (IPCA) and Resource Allocating Network with Long-Term Memory (RAN-LTM) are effectively combined to implement this idea. Since IPCA updates a feature space incrementally by rotating the eigen-axes and increasing the dimensions, the inputs of a neural classifier must also change in their values and the number of input variables. To solve this problem, we derive an approximation of the update formula for memory items, which correspond to representative training samples stored in the long-term memory of RAN-LTM. With these memory items, RAN-LTM is efficiently reconstructed and retrained to adapt to the evolution of the feature space. This function is incorporated into our face recognition system. In the experiments, the proposed incremental learning model is evaluated over a self-compiled video clip of 24 persons. The experimental results show that the incremental learning of a feature space is very effective to enhance the generalization performance of a neural classifier in a realistic face recognition task.

Accumulation of allo-isocitric acid by a Penicillium strain.

The occurrence of L(S)-allo-isocitric acid in nature, as a new fungal product, was first found in the culture medium of Pen. purpurogenum Stoll var. rubri-sclerotium Thom. No. 1148. The acid was obtained as its gamma-lactone in a crystalline form. Some chemical and physical characters were described. The acid was the only one detectable acid accumulated by its fungus in the given condition, and the yield of the acid by weight exceeded about 70% of the consumed glucose.

Fuzzy least squares support vector machines for multiclass problems.

In least squares support vector machines (LS-SVMs), the optimal separating hyperplane is obtained by solving a set of linear equations instead of solving a quadratic programming problem. But since SVMs and LS-SVMs are formulated for two-class problems, unclassifiable regions exist when they are extended to multiclass problems. In this paper, we discuss fuzzy LS-SVMs that resolve unclassifiable regions for multiclass problems. We define a membership function in the direction perpendicular to the optimal separating hyperplane that separates a pair of classes. Using the minimum or average operation for these membership functions, we define a membership function for each class. Using some benchmark data sets, we show that recognition performance of fuzzy LS-SVMs with the minimum operator is comparable to that of fuzzy SVMs, but fuzzy LS-SVMs with the average operator showed inferior performance.

n-Hexane sensitivity of Escherichia coli due to low expression of imp/ostA encoding an 87 kDa minor protein associated with the outer membrane.

Most Escherichia coli strains are resistant to n-hexane. E. coli OST4251 is a n-hexane-sensitive strain that was constructed by transferring the n-hexane-sensitive phenotype from a n-hexane-sensitive strain by P1 transduction. OST4251 is resistant to diphenyl ether, which is less harmful than n-hexane to micro-organisms. The genetic determinant responsible for this subtle difference in the solvent resistance is mapped at 1.2 min on the E. coli chromosome. Nucleotide sequence analysis showed that IS2 and IS5 had integrated upstream of the imp/ostA structural gene in OST4251. The integration of IS2 decreased the activity of the imp/ostA promoter. A product of the gene was identified immunologically as an 87 kDa minor protein associated with the outer membrane. Upon transformation with plasmids containing the imp/ostA gene, OST4251 produced a high level of the gene product in the membrane and acquired n-hexane resistance. Thus, the low level of promoter activity resulted in low Imp production and the n-hexane-sensitivity phenotype. It is likely that the gene product contributes to n-hexane resistance by reducing the influx of n-hexane.