Akihito Kazuno

Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence: New predictive evaluation of anastomotic leakage after esophagectomy.

AbstractAnastomotic leakage is considered as an independent risk factor for postoperative mortality after esophagectomy, and an insufficient blood flow in the reconstructed conduit may be a risk factor of anastomotic leakage. We investigated the clinical significance of blood flow visualization by indocyanine green (ICG) fluorescence in the gastric conduit as a means of predicting the leakage of esophagogastric anastomosis after esophagectomy.Forty patients who underwent an esophagectomy with gastric conduit reconstruction were prospectively investigated. ICG fluorescence imaging of the gastric conduit was detected by a near-infrared camera system during esophagectomy and correlated with clinical parameters or surgical outcomes.In 25 patients, the flow speed of ICG fluorescence in the gastric conduit wall was simultaneous with that of the greater curvature vessels (simultaneous group), whereas in 15 patients this was slower than that of the greater curvature vessels (delayed group). The reduced speed of ICG fluorescence stream in the gastric conduit wall was associated with intraoperative blood loss (P = 0.008). Although anastomotic leakage was not found in the simultaneous group, it occurred in 7 patients of the delayed group (P < 0.001). A flow speed of ICG fluorescence in the gastric conduit wall of 1.76 cm/s or less was determined by a receiver operating characteristic (ROC) curve, identified as a significant independent predictor of anastomotic leakage after esophagectomy (P = 0.004).This preliminary study demonstrates that intraoperative evaluation of blood flow speed by ICG fluorescence in the gastric conduit wall is a useful means to predict the risk of anastomotic leakage after esophagectomy.

Impact of body mass index on postoperative complications and long-term survival in patients with esophageal squamous cell cancer.

Undernutrition and cachexia have been suggested to be risk factors for postoperative complications and survival in cancer patients. The aim of this study was to investigate whether body mass index (BMI) is related to the short-term and long-term outcomes in patients who undergo an esophagectomy for the resection of esophageal squamous cell cancer (ESCC). Three hundred forty patients who underwent an esophagectomy for the resection of ESCC between 2003 and 2008 were retrospectively reviewed. The patients were divided into two groups: an L-BMI group characterized by a BMI < 18.5 kg/m(2) and an N-BMI group characterized by a BMI ≥ 18.5 kg/m(2). Clinical and pathological outcome were compared between groups. The study included 40 patients in the L-BMI group and 300 patients in the N-BMI group. A clinicopathological assessment showed that nodal involvement was seen more frequently in the L-BMI group (P = 0.016). Pulmonary complications seemed to occur more frequently in the L-BMI group (P = 0.006). The 5-year overall survival rate was higher in the N-BMI group (63.6%) than in the L-BMI group (32.3%) (P < 0.001). The 5-year disease-free survival rate was also higher in the N-BMI group (58.0%) than in the L-BMI group (33.6%) (P = 0.001). In multivariate analysis, the BMI (hazard ratio, 2.154; 95% CI, 1.349-3.440, P = 0.001) was found to be an independent prognostic factor for overall survival. Our data suggested that a lower BMI not only increased pulmonary complications but also impaired overall and disease-free survival after an esophagectomy for the resection of ESCC.

Laparoscopic mesh repair of adult diaphragmatic hernia: A report of two cases

Congenital diaphragmatic hernia is very rare in adults. The first choice of treatment is surgery, but the optimal surgical method remains unclear. We performed laparoscopic surgeries for two types of congenital diaphragmatic hernias using a novel mesh coated with a chemically modified substance. The first patient was a 65‐year‐old man with a Bochdalek hernia without a hernial sac, and the other patient was an 80‐year‐old woman with a Morgagni hernia with a hernial sac. The short‐term outcomes of both cases were good, and laparoscopic repair seems to be a useful strategy regardless of the presence or absence of a hernial sac.

Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation.

Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2–8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.

Technique of the double-channel ESD method performed with an EEMR tube

Endoscopic submucosal dissection (ESD) recently has been aggressively performed to treat superficial esophageal cancer; however, it is difficult to secure a good field of view for mucosal dissection, and the technique requires considerable skill. We have developed a double-channel ESD method using an endoscopic esophageal mucosal resection (EEMR) tube that makes it possible to perform the submucosal dissection with a good field of view while applying countertraction. Countertraction is achieved by maneuvering a fine grasping forceps inserted through the side channel of the EEMR tube, and the field of view of the submucosal dissection layer can be easily exposed. This technique can be performed while constantly observing the submucosal dissection layer with a stable field of view, and it is also easy to handle the blood vessels. Moreover, there is no disturbance of the field of view by the dissected mucosa.

Clinical Significance of New Magnetic Resonance Thoracic Ductography Before Thoracoscopic Esophagectomy for Esophageal Cancer

BackgroundPreoperative simulation of the thoracic duct using magnetic resonance thoracic ductography (MRTD) would enable a safe lymph node dissection near the thoracic duct and the prevention of chylothorax after an esophagectomy. The aim of this study was to determine whether MRTD is useful for preventing injury to the thoracic duct during surgery and for reducing the incidence of chylothorax after surgery.MethodsWe evaluated 130 patients who underwent preoperative MRTD followed by a thoracoscopic esophagectomy for the treatment of thoracic esophageal cancer between August 2014 and April 2017 (MRTD group). These patients were then compared with 160 patients with esophageal cancer who underwent a thoracoscopic esophagectomy without preoperative MRTD (non-MRTD group).ResultsFour patients in the non-MRTD group developed Type IIIB chylothorax (International Consensus on Standardization), while none of the patients in the MRTD group developed Type III chylothorax. Some type of abnormal finding was found during MRTD in 24 patients (18.5%). Among them, 13 patients (10.0%) exhibited abnormal divergence, which was the most frequent finding, followed by 5 patients (3.8%) with window formation and 2 patients (1.5%) with stitch formation.ConclusionsThe present study revealed the frequencies of abnormal findings of the thoracic duct and of patients with false-negative MRTD findings. Injury to the thoracic duct can be avoided through the use of appropriate care during procedures performed in patients with abnormal findings on preoperative MRTD.

Voluntary Exercise Positively Affects the Recovery of Long-Nerve Gap Injury Following Tube-Bridging with Human Skeletal Muscle-Derived Stem Cell Transplantation

The therapeutic effects of voluntary exercise on the recovery of long-gap nerve injury following the bridging of an acellular conduit filled with human skeletal muscle-derived stem cells (Sk-SCs) have been described. Human Sk-SCs were sorted as CD34+/45− (Sk-34) cells, then cultured/expanded under optimal conditions for 2 weeks. Surgery to generate a long-gap sciatic nerve injury was performed in athymic nude mice, after which the mice were divided into exercise (E) and non-exercise (NE) groups. The mice were housed in standard individual cages, and voluntary exercise wheels were introduced to the cages of the E group one week after surgery. After 8 weeks, the human Sk-34 cells were actively engrafted, and showed differentiation into Schwann cells and perineurial cells, in both groups. The recovery in the number of axons and myelin in the conduit and downstream tibial nerve branches, and the lower hindlimb muscle mass and their tension output, was consistently higher by 15–25% in the E group. Moreover, a significantly higher innervation ratio of muscle spindles, reduced pathological muscle fiber area, and acceleration of blood vessel formation in the conduit were each observed in the E group. These results showed that the combined therapy of tube-bridging, Sk-34 cell transplantation, and voluntary exercise is a potentially practical approach for recovery following long-gap nerve injury.

Clinicopathological significance of laminin-5γ2 chain expression in superficial esophageal cancer

The glycoprotein laminin 5γ2 chain (LN-5γ2) has recently become a focus of increased interest and investigation as a marker of invasion in gastrointestinal malignancies. We investigated the significance of LN-5γ2 expression as a prognostic factor in superficial esophageal cancer. The study population consisted of 87 patients who had undergone a transthoracic esophagectomy and three-field lymphadenectomy for the treatment of superficial esophageal cancer at Tokai University Hospital. Formalin-fixed, paraffin-embedded sections of the resected specimens were examined using immunohistochemical staining and hematoxylin and eosin staining to assess the correlations between the LN-5γ2 expression pattern and the clinicopathological factors (age, sex, T-factor, N-factor, ly-factor, v-factor, degree of differentiation, infiltrative growth pattern, tumor node metastasis classification of malignant tumors [TNM] stage, etc.) and the patient outcome. The expression pattern of LN-5γ2 was classified into an extracellular type (E type), characterized by the staining of extracellular matrix such as the basement membrane and the stroma (31 cases, 35.6%), and a cytoplasmic type (C type), characterized by the staining of the cytoplasm in the cancer cells (56 cases, 64.6%). The expression pattern was not correlated with any of the clinicopathological factors that were assessed. However, univariate analyses of the survival analysis data showed that the N-factor (P = 0.011), TNM stage (P = 0.011), and LN-5γ2 C type (P = 0.017) were prognostic factors. A multivariate analysis revealed that the N-factor (P = 0.049) and LN-5γ2 C type (P = 0.048) were prognostic factors. In the survival analysis, a univariate analysis of the 75 T1b cases also showed that the N-factor (P = 0.048), TNM stage (P = 0.048), and LN-5γ2 C type (P = 0.029) were prognostic factors, while a multivariate analysis showed that the LN-5γ2 C type (P = 0.035) was a prognostic factor. The C type expression of LN-5γ2, i.e. confined to the cytoplasm, was correlated with an unfavorable outcome among the patients with superficial esophageal cancer in the present series. Observation of the LN-5γ2 expression pattern may be useful for the diagnosis of highly malignant tumors.

Expression of vasohibin‑1 and ‑2 predicts poor prognosis among patients with squamous cell carcinoma of the esophagus

Vasohibin (VASH) -1 and -2 are novel angiogenic regulators. The aim of the present study was to assess the prognostic values of VASH1 expression and VASH2 expression in esophageal squamous cell carcinoma (ESCC). A total of 209 patients with ESCC were investigated. Resected tumor specimens were immunostained using anti-CD34 antibody, anti-VASH1 antibody and anti-VASH2 antibody. The ratio of the microvessels density and the VASH1 density as the VASH1-positive ratio were defined and the patients were divided into two groups (a high VASH1 group and a low VASH1 group) according to the average value. The patients were also divided into two groups (a high VASH2 group and a low VASH2 group) according to VASH2 expression upon immunostaining. The clinical outcomes of these two groups were then evaluated. The high VASH1 group contained 106 patients (50.7%). The high VASH2 group contained 48 patients (23.0%). Long-term survival was significantly poorer in the high VASH1 group compared with that in the low VASH1 group. A slight correlation between VASH1 expression and VASH2 expression was observed. The low VASH1/low VASH2 group had a better prognosis than the other three groups with different combinations of VASH1 and VASH2 expression levels. The present study showed that high VASH1 expression and high VASH2 expression may be novel independent predictors of a poor prognosis in patients with ESCC and that a slight correlation between VASH1 and VASH2 expression existed. The present findings suggest that combined evaluation of VASH1 and VASH2 expression should provide an improved understanding of their clinicopathological features.

Effectiveness of neoadjuvant chemotherapy with etoposide and cisplatin followed by surgery for esophageal neuroendocrine carcinoma: a case report

Patients with esophageal neuroendocrine carcinoma (ENEC), which is a rare disease, are considered to have a poor prognosis because of aggressive progression and widespread dissemination (1). The optimal treatment strategy for ENEC remains to be established. In this report, we describe a patient with ENEC who successfully achieved a pathologically complete response with neoadjuvant chemotherapy.