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Vasohibin-1 (VASH1) is an angiogenesis inhibitor, while vasohibin-2 (VASH2) is a proangiogenic factor. The roles of VASH1 and VASH2 expression in gastroenterological cancers remain unclear. We searched for relevant literature, specifically studies on gastroenterological cancer, and evaluated the relationship between VASH expression and clinical outcomes. Nine studies on VASH1 involving 1,574 patients were included. VASH1 expression was associated with the TNM stage [OR (odds ratio) 2.05, 95% CI (confidence interval) 1.24-3.40], lymph node metastasis (OR 1.79, 95% CI 1.24-2.58), lymphatic invasion (OR 1.95, 95% CI 1.41-2.68), and venous invasion (OR 2.49, 95% CI 1.60-3.88); poor clinical outcomes were associated with high VASH1 expression. High VASH1 expression was associated with a significantly shorter overall survival (OS) [HR (hazard ratio) 1.69, 95% CI 1.25-2.29] and disease-free survival (DFS) (HR 2.01, 95% CI 1.28-3.15). Three studies on VASH2 involving 469 patients were analyzed. VASH2 expression was associated with the TNM stage (OR 4.21, 95% CI 1.89-9.51) and venous invasion (OR 2.10, 95% CI 1.15-3.84); poor clinical outcomes were associated with high VASH2 expression. High VASH2 expression was associated with a significantly lower OS (HR 1.61, 95% CI 1.09-2.37). In conclusion, high VASH1 and VASH2 expression levels were associated with poor clinical outcomes and prognosis in patients with gastroenterological cancers.

Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). In recent years, induction chemotherapy (ICT) has been reported to yield high response rates for locally advanced ESCC, and the efficacy and safety of ICT followed by conversion surgery (CS) have been investigated. Multimodal treatment, combining surgery with induction chemoradiotherapy (ICRT) or ICT, is necessary to improve ESCC prognosis. CS is generally performed for locally advanced ECC after ICRT or ICT when tumor downstaging is achieved, although its prognostic benefit remains controversial. The Japan Clinical Oncology Group (JCOG) has conducted a three-arm phase III randomized controlled trial (JCOG1510) to confirm the superiority of DCF (docetaxel, cisplatin, and 5-fluorouracil) ICT, over conventional dCRT, among patients with initially unresectable ESCC. In recent years, researchers have reported favorable outcomes of induction therapy followed by CS and salvage surgery, after dCRT or systemic immunochemotherapy. In this review, we will describe the latest developments in the multimodal treatment including chemotherapy, CRT, surgery, and immunotherapy, which may improve oncological and survival outcomes for patients with cT4 ESCC.

Surgical cases of robot-assisted thoracoscopic esophagectomy (RAMIE) is increasing because of the advantages of robotic system. We introduced RAMIE in 2019 and standardized the surgical procedure. The usefulness of RAMIE was examined by classifying surgical cases into early and late periods and comparing the surgical results. Fifty-four patients who underwent RAMIE were enrolled in the study. All patients underwent D2 or higher lymph node (LN) dissection, gastric tube reconstruction, and R0 surgery. The patients were divided into two groups, 26 cases in the first half up to December 2020 and 28 cases in the second half after January 2021. The patient background, surgical technique, and short-term results were compared. The tumor staging was based on the UICC 8th version. Thoracic surgery time was 274 minutes, the chest bleeding volume was 30 mL, and the postoperative hospital stay was 19 days (median). In the late stage, patients with clinical thoracic LN metastasis (p = 0.01) and advanced stage (p = 0.006) were higher than those in the early period. There were significantly more cases of thoracic duct resection and D3 dissection in the late period (p = 0.02, p = 0.009). No differences in postoperative complications and intra-hospital death was observed, however the postoperative hospital stay was significantly shortened in the late period (p = 0.001). Thorough mediastinal LN dissection by RAMIE could be safely performed by standardizing and improving the surgical procedures. RAMIE has several issues such as higher cost associated with equipment and longer operative time, but it is possible to perform precise procedures with solo surgery, and it is expected that cost reduction effects will be expected in terms of the number of participants in surgery and the length of hospital stay after surgery.

The recurrence rates in patients with esophageal cancer who are treated by curative esophagectomy is reported to be 29-43%. Recently, the concept of oligometastasis recurrence (OLR) has gained attention. To clarify the relationship between treatment strategy and prognosis of patients with OLR after esophagectomy. We included 124 patients with recurrence among 446 patients who underwent esophagectomy for esophageal cancer. OLR was defined as five or fewer recurrences in a single organ or five or fewer recurrences in a single lymph node. Patients were divided into two groups: OLR and non-OLR group. Recurrence within 6 months after surgery was defined as early recurrence. The relationship between early recurrence and prognosis was examined. We focused on liver and lung metastases and examined treatment methods and prognosis. Of the recurrence patients, 40 (32%) were in the OLR group and 84 (78%) were in the non- OLR group. The overall survival was 49 months in the OLR group and 17 months in the non-OLR group (p Oligometastasis is related to prognosis in patients with recurrence after esophagectomy, and patients with early recurrence or liver recurrence may have a poor prognosis.

In a phase III study, nivolumab treatment significantly prolonged survival compared with taxanes in patients with unresectable advanced or recurrent esophageal cancer who had become intolerant to first-line chemotherapy with 5-FU and platinum-based agents. We will report our experience and results of treatment with nivolumab at our hospital. The subjects were 46 patients treated with nivolumab for unresectable advanced or recurrent esophageal cancer at our hospital from January 2019 to December 2021. Clinical factors and treatment effects were investigated. The initial response was PR in 12 cases, SD in 18 cases, PD in 12 cases, and unevaluable in 4 cases. Median duration of nivolumab treatment was 3 months (1-18 months). Adverse effects grade 3 were found in 9 cases and grade 2 in 9 cases. Nivolumab was discontinued in 5 cases (10.8%) due to adverse effects. Compared between cases who discontinued nivolumab within 2 months due to ineffectiveness or adverse effects and those who were able to continue for more than 2 months, overall survival was significantly prolonged in the latter group (median OS: 23.8 vs. 36.8 months, p=0.05). In patients with unresectable advanced or recurrent esophageal cancer who responded to nivolumab, it was suggested that the drug may improve prognosis. The incidence of unsustainable adverse effects is relatively high, and it is important to control adverse effects.

Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy. The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated. Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07 cm/s or less (P

Vasohibins (VASH), which are angiogenesis regulators, consist of Vasohibin-1 (VASH1) and Vasohibin-2 (VASH2). VASH1 is an angiogenesis inhibitor, while VASH2 is a proangiogenic factor. Patients with esophageal squamous cell carcinoma (ESCC) with high tumor expression levels of VASH1 and VASH2 have been reported to show a poor prognosis. The clinical significance of VASH concentrations in the blood of patients with ESCC has not yet been investigated. Plasma samples from 89 patients with ESCC were analyzed, and the relationships between the plasma VASH concentrations and the clinicopathological factors of the patients were evaluated. Immunohistochemical examination (IHC) of the resected tumor specimens for VASH was performed in 56 patients, and the correlation between the plasma VASH concentrations and tumor expression levels of VASH was analyzed. The patient group with high plasma concentrations of VASH1 showed a higher frequency of lymph node metastasis (P = 0.01) and an invasive growth pattern (P = 0.05). Furthermore, poorly differentiated cancer occurred at a higher frequency in the patient group with high plasma concentrations of VASH2 (P

Background/Aim: In the Japanese Classification of Gastric Carcinoma, T4a gastric cancer is defined as tumor invasion contiguous to the serosa or penetrating the serosa with exposure to the peritoneal cavity. The aim of this study was to assess the impact of T4a subclassification of gastric cancer on survival. Patients and Methods: A total of 326 patients with T4a cancer who had undergone gastrectomy were enrolled. The T4a tumors were classified into two groups: serosa-contiguous or serosa-exposed. Results: The serosa-exposed group had a significantly worse prognosis, and multivariate analysis identified the T4a subclass as an independent prognostic factor. Analysis of the risk factors for recurrence identified the T4a subclass as a significant risk factor for peritoneal recurrence in patients undergoing curative gastrectomy. Conclusion: The serosa-contiguous and serosa-exposed subgroups of T4a gastric cancer showed different biological behaviors. These groups may need to be treated as separate.

The thoracic inlet space might influence the blood vessel perfusion in the gastric conduit. The purpose of this study was to clarify the impacts of the thoracic inlet space on blood vessel perfusion in the gastric conduit and anastomotic leakage after esophagectomy.One hundred and forty-two esophageal cancer patients underwent esophagectomy followed by gastric conduit reconstruction via the retrosternal route. The blood flow speed in the gastric conduit was measured using indocyanine green fluorescence before and after reconstruction. Parameters at the thoracic inlet space were measured using CT. We then investigated the correlation between these two parameters and whether they could predict anastomotic leakage after esophagectomy.Blood flow speed in the gastric conduit was slower after reconstruction than before reconstruction (P 0.001). The incidence of anastomotic leakage (n = 23) was higher among patients with a delayed blood flow speed before reconstruction (n = 27) than among those with a non-delayed blood flow speed before reconstruction (n = 115) (P 0.001). Among the patients with a non-delayed blood flow speed before reconstruction, the thoracic inlet area (TIA, sternum-tracheal distance × clavicle head distance) was positively correlated with the blood flow speed after reconstruction (P = 0.023) and was identified as an independent predictor of anastomotic leakage (P 0.001).A narrow TIA was associated with a delayed blood flow speed in the gastric conduit after reconstruction and was capable of predicting anastomotic leakage in the patients with a non-delayed blood flow speed before reconstruction.

Background Recently, due to increasing reports of stenosis after esophagojejunostomy created using circular staplers and a transorally inserted anvil (OrVil™) following laparoscopic proximal gastrectomy (LPG) and total gastrectomy (LTG), linear staplers are being used instead. We investigated our preventive procedure for esophagojejunostomy stenosis following use of circular staplers. Methods Since the anastomotic stenosis is considered to be mainly caused by tension in the esophageal and jejunal stumps at the anastomotic site, we have been performing procedures to relieve this tension, by cutting off the rubber band and pushing the shaft of the circular stapler toward the esophageal side, since July 2015. We retrospectively compared the incidence of anastomotic stenosis in cases of LPG and LTG performed before July 2015 (early phase, 30 cases) versus those performed after this period (later phase, 22 cases). Results Comparison of the incidence of anastomotic stenosis according to the type of surgery, LPG or LTG, and between the two time periods versus all cases, indicated a significantly lower incidence in the later phase than in the early phase (4.5 vs. 26.7%, p p Conclusions It is possible to use a circular stapler during laparoscopic esophagojejunostomy, as with open surgery, if steps to reduce tension on the anastomotic site are undertaken. These procedures will contribute to the spread of safe and simple laparoscopic anastomotic techniques.

Background Surgery for cases of thoracic esophageal cancer with a right aortic arch is rare, and the anatomic abnormalities in such patients necessitate a different surgical approach. Since the position of the recurrent laryngeal nerve often differs from the usual in these cases, the lymph node dissection around the recurrent laryngeal nerve, which is an important step in surgery for thoracic esophageal cancer, requires careful attention. There are some reports on the usefulness of intraoperative recurrent laryngeal nerve monitoring during esophageal cancer surgery. Herein, we report a case of successful thoracoscopic esophagectomy for esophageal cancer in a patient with a right aortic arch using intraoperative recurrent laryngeal nerve monitoring. Case presentation A 70-year-old man was diagnosed as having esophageal cancer (Ut, type 0-IIc, T1b/MtLt, type 0-IIc, T1b, N2, M0, cStage II) and was treated by neoadjuvant chemoradiotherapy followed by radical surgery. Preoperative CT examination revealed a right aortic arch, and based on the findings of 3D-CT, we classified the right aortic arch as type IIIB1 (Edwards classification), which is the most frequent type of right aortic arch. We performed thoracoscopic esophagectomy via a left thoracic approach with the patient placed in the prone position, cervical esophagogastric conduit reconstruction via the retrosternal route, and three-field lymph node dissection. Although Kommerell’s diverticulum could be easily confirmed, the descending aorta took a meandering course, making it difficult for the esophagus to be mobilized and detached and therefore also to identify the ductus arteriosus and left recurrent laryngeal nerve. Intraoperative recurrent laryngeal nerve monitoring using NIM-RESPONSE® 3.0 (Medtronic Japan, Tokyo, Japan) allowed the position of the left recurrent laryngeal nerve to be accurately determined, and upper mediastinal lymph node dissection and mobilization of the upper thoracic esophagus were performed safely. Postoperatively, the patient showed no evidence of recurrent laryngeal nerve palsy, but needed conservative treatment for anastomotic leakage. The patient was discharged 46 days after the surgery. Conclusion It was suggested that intraoperative recurrent laryngeal nerve monitoring is useful in esophageal cancer with a right aortic arch undergoing surgery, in whom anatomic abnormalities of the recurrent laryngeal nerve can be expected.

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.

Preoperative 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. We 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). Four 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. The 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.

Basaloid squamous cell carcinoma (BSC) of the esophagus is classified as an epithelial malignant tumor and is a rare variant of squamous cell carcinoma (SCC). Most previous reports have suggested that advanced BSC has a poorer prognosis than typical SCC because of its high biological malignancy, but the biological activity of superficial BSC remains unclear. Twenty cases of superficial BSC, which underwent surgical resection in Tokai University Hospital between January 2004 and December 2013, were analyzed retrospectively. Among these cases, 19 cases with a T1 depth of invasion (BSC group) were compared with 180 cases of SCC that were resected during the same period and were pathologically diagnosed as T1 (SCC group). The frequency of lymph node metastasis in the T1 BSC group was significantly lower (2 patients, 11%) than that in the SCC group (84 patients, 47%) (P = 0.005). The frequency of lymphatic invasion in the BSC group was also lower (9 patients, 47%) than that in the SCC group (131 patients, 73%) (P = 0.021). The pathological type of the metastatic lymph node was BSC in all the superficial BSC cases with lymph node metastasis. This study demonstrated that lymph node metastasis was less likely to occur in cases with superficial BSC than in cases with superficial SCC.

A 65-year-old woman with no significant medical history visited the emergency department complaining of epigastric discomfort. A computed tomography of the thorax and abdomen showed the attenuation of the pulmonary artery and a posterior mediastinal hematoma. Angiography showed a tortuous esophageal branch of the left gastric artery and a pseudoaneurysm, and during the later phase, the left lower lobe of the lung was enhanced, and finally, the left pulmonary vein was enhanced. We considered that the patient was exhibiting hypoperfusion of the left pulmonary artery arising from left pulmonary artery hypoplasia, since the left lung was supplying the systemic circulation. Transcatheter arterial embolization was performed. The patient has not experienced any recurrence of a ruptured pseudoaneurysm or epigastric discomfort. Here, we report the first documented case of pulmonary artery hypoplasia associated with posterior mediastinal hematoma accompanied by a ruptured aneurysm of the left gastric artery.

The present study investigated prognostic factors in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) among various clinicopathological features related to neoadjuvant chemotherapy (NAC) and surgery, and the indications for additional treatment after surgery were considered. A total of 113 patients with clinical stage II or III ESCC, who had undergone NAC followed by a thoracic esophagectomy with a three-field lymphadenectomy were retrospectively reviewed. NAC consisted of either two courses of cisplatin and 5-fluorouracil or three courses of docetaxel, cisplatin and 5-fluorouracil, with a new course beginning every 3 weeks. The overall survival (OS) rate was poorer in the pN-positive group than in the pN-negative group (P

SUMMARY The relationship between lymphovascular invasion (LVI) and prognosis in patients with superficial esophageal squamous cell carcinoma (SESCC) is unclear. The aim of this study is to evaluate prognostic factors in patients with lymph node-negative SESCC. A total of 195 patients with pathologically confirmed T1a-MM, T1b, and lymph node-negative SESCC were retrospectively reviewed in this study. Overall, the disease-free survival (DFS) rate was poorer in the lymphatic invasion-positive group than in the lymphatic invasion-negative group (p = 0.002) and a multivariate analysis suggested that lymphatic invasion was the only independent prognostic factor of DFS in patients with lymph node-negative SESCC (HR = 4.075, p = 0.005). Distant organ recurrence occurred in one patient (1/52, 1.9%) in the T1b-SM2 group and in six patients (6/61, 9.7%) in the T1b-SM3 group; all of these patients had LVI. LVI-positive patients had a poorer DFS than invasion-negative patients in the T1b-SM2 and SM3 groups (p = 0.026), and a multivariate analysis suggested that LVI was the only independent prognostic factor of DFS in patients with lymph node-negative SM2 and SM3 SESCC (HR = 5.165, p = 0.031). Lymph node-positive patients had a significantly poorer DFS rate than lymph node negative and LVI positive patients among the SM2 and SM3 SESCC patients (p = 0.018). The present results suggested that LVI was an independent prognostic factor in patients with SM2 and SM3 lymph node-negative SESCC; however their prognosis was not worse than that of patients with lymph node-positive SM2 and SM3 SESCC, for whom adjuvant therapy is indicated as a standard treatment.

SUMMARY Nononcological prognostic factors in superficial esophageal squamous cell carcinoma (SESCC) patients remain unclear. The aim of this study is to evaluate the relationship between sarcopenia and surgical outcome in patients with SESCC who had undergone definitive surgery. A total of 194 SESCC patients who had undergone thoracic esophagectomy with three-field lymphadenectomy without neoadjuvant therapy at Tokai University Hospital between January 2006 and December 2015 were analyzed retrospectively. Manual tracing using CT imaging was used to measure the cross-sectional areas of the skeletal muscle mass. The cutoff values for the skeletal muscle index used to define sarcopenia were based on the results of a previous study. Twenty-eight patients (14.4%) had sarcopenia, while the remaining 166 patients (85.6%) did not. A multivariate analysis suggested that sarcopenia was an independent risk factor for postoperative pulmonary complications (OR = 3.232, P = 0.026). The overall survival rate and the disease-free survival rate were both significantly worse in the sarcopenia group than in the nonsarcopenia group (P

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.

Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for esophageal squamous cell carcinoma diagnosed as clinical stage II/III in Japan, and the indications for chemotherapy for esophageal cancer are increasing. Here, we report two patients who suffered from upper gastrointestinal perforation during NAC for esophageal cancer. NAC with cisplatin and 5-fluorouracil (CF regimen) was performed for both patients. Emergency operations were performed in all the patients prior to curative surgery for esophageal cancer. Endoscopic examination should be performed to confirm peptic ulcers or scars before NAC with CF regimen, and premedication with a proton pump inhibitor and the avoidance of steroid use are recommended for patients with a history of peptic ulcer to prevent perforation during NAC. Whether the occurrence of perforations during NAC is a risk factor for recurrence or a poor prognosis should be investigated in patients with esophageal cancer.

Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk-MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs were isolated from green fluorescence protein transgenic mice and then expanded and transplanted with PGA felt for the hybrid transplantation (HY group) into the RLN transected mouse model. Transplantation of culture medium (M group) and PGA + medium (PGA group) were examined as controls. After eight weeks, trans-oral video laryngoscopy demonstrated 80% recovery of spontaneous vocal-fold movement during breathing in the HY group, whereas the M and PGA groups showed wholly no recoveries. The Sk-MSCs showed active engraftment confined to the damaged RLN portion, representing favorable prevention of cell diffusion on PGA, with an enhanced expression of nerve growth factor mRNAs. Axonal re-connection in the HY group was confirmed by histological serial sections. Immunohistochemical analysis revealed the differentiation of Sk-MSCs into Schwann cells and perineurial/endoneurial cells and axonal growth supportive of perineurium/endoneurium. The number of axons recovered was over 86%. These results showed that the stem cell and cytokine delivery system using hybrid transplantation of Sk-MSCs/PGA-felt is a potentially practical and useful approach for the recovery of transected RLN.

Background Mixed adenoneuroendocrine carcinoma (MANEC) is a tumor of the gastrointestinal tract that contains both exocrine and endocrine components, with each component exceeding 30% of the total tumor area. Because MANECs are exceedingly rare, no therapeutic strategies have been established yet. Case presentation An 81-year-old man was referred to our hospital with a 5-month history of dysphagia. Esophagogastroduodenoscopy revealed an ulcerated mass in the lower thoracic esophagus, extending up to the esophagogastric junction (33 to 40 cm from the incisors). The initial biopsy diagnosis was adenocarcinoma. Computed tomography revealed no evidence of lymph node or distant metastasis. The patient was treated by thoracoscopic esophagectomy with three-field lymph node dissection and gastric tube reconstruction via a posterior mediastinal approach, under the diagnosis of esophagogastric junctional cancer (T3N0M0, stage IIA). Histopathological examination revealed two distinct components, namely, a neuroendocrine carcinoma component and an adenocarcinoma component, and the patient was diagnosed as having mixed adenoneuroendocrine carcinoma (MANEC). He presented with liver metastasis 6 months after the surgery. Thereafter, the tumor became even more aggressive, and the patient died 8 months after the surgery. Conclusions We report a patient with MANEC of the esophagogastric junction. Close attention should be paid to such patients, as MANEC can be a highly aggressive tumor, showing rapid progression. In the treatment of MANEC, it is necessary to carefully consider the pathological features in each individual case.

Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgically excised pair-wise from 35 patients with esophageal cancer. Following tissue homogenization and metabolite extraction, a total of 110 compounds were absolutely quantified by CE-TOFMS. We compared the concentrations of the metabolites between Ts and NTs, between pT1 or pT2 (pT1-2) and pT3 or pT4 (pT3-4) stage, and between node-negative (pN-) and node-positive (pN+) samples. Principal component analysis and hierarchical clustering analysis revealed clear metabolomic differences between Ts and NTs. Lactate and citrate levels in Ts were significantly higher (P=0.001) and lower (P

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.

The Wnt signaling pathway is widely implicated in various types of cancer. Canonical Wnt signaling, including Wnt3a, may be a key component of cancer progression or chemoresistance. Consequently, it was hypothesized that Wnt3a expression may be a prognostic factor of esophageal squamous cell carcinoma (ESCC) due to its roles in chemoresistance and tumor progression. The aim of the present study was to investigate the association between Wnt3a expression and prognosis in patients with ESCC. Wnt3a expression was evaluated in resected specimens from 139 patients with thoracic ESCC who were subjected to curative surgery without neoadjuvant therapy in Tokai University Hospital between 2007 and 2009. Samples were assessed using immnohistochemistry. Patients with ESCC were divided into two groups according to the expression of Wnt3a in tumor tissue. The influence of Wnt3a expression on clinicopathological findings and prognosis of ESCC were subsequently investigated. Immnohistologically, 68 cases were Wnt3a-positive in the cytoplasm of cancer cells, whereas 71 cases were negative. Multivariate analysis by Cox proportional hazard model showed the association between pN (HR=3.539, P=0.001), venous invasion (HR=2.798, P=0.012), Wnt3a expression (HR=1.691, P=0.046) and overall survival (OS). OS rate and disease-free survival rate were poorer in Wnt3a-positive group compared with those in the Wnt3a-negative group as indicated by the log-rank test (P=0.012 and P=0.023, respectively). In pathological stages I and II, there was no significant difference in the OS rate between Wnt3a-positive and Wnt3a-negative groups; however, the OS rate of the Wnt3a-positive group was significantly worse than that of Wnt3a-negative group in pathological stage III (log rank test; P=0.017). Wnt3a-positive patients with recurrence had a significantly poorer prognosis compared with Wnt3a-negative patients (log-rank test; P=0.023). The present findings suggested that Wnt3a may be a prognostic factor of ESCC.

Background Plication of an esophageal hiatus during surgery for esophageal hiatal hernia is a common practice; however, a mesh may be used if the hiatus is markedly enlarged. Recently, various late complications occurring as a result of mesh-induced esophageal and/or gastric wall injuries have been reported. Case presentation A 71-year-old woman presented at a neighborhood clinic in November 2010 with chief complaints of respiratory distress on exertion and heartburn. She was diagnosed as having a large esophageal hiatal hernia and was treated at our hospital using a laparoscopic Toupet fundoplication with mesh repair of the esophageal hiatus. Two years and 1 month after the operation, the patient complained of a bowel obstruction. An upper gastrointestinal endoscopy revealed that part of the mesh had extruded into the esophageal lumen, resulting in ulceration and stricture of the esophageal wall. Endoscopic balloon dilatation failed to improve the esophageal stricture. In July 2012, the patient underwent a lower esophagectomy with proximal gastrectomy and was discharged on the 25th hospital day. Conclusions We experienced a rare case requiring surgical treatment for a mesh-induced esophageal wall injury after surgery for a giant esophageal hiatal hernia. The selection of a soft, durable mash and its firm securement at a position distant from the gastrointestinal wall may be important to avoid late esophageal wall injury.

Background Most of benign esophageal strictures caused by gastroesophageal reflux are short segments and can be treated by an endoscopic dilatation, but cases of long-segment stenosis requiring an esophagectomy are rare. Case presentation A 62-year-old woman had undergone emergency surgery for a giant ovarian tumor rupture at another hospital. A duodenal perforation occurred after surgery but improved with conservative treatment. She had undergone long-term nasogastric tube placement for 4 months because she was on a mechanical ventilator and did not receive proton pump inhibitors (PPIs). Thereafter, the patient experienced dysphagia. An esophagogastroduodenoscopy (EGD) revealed circumferential reflux esophagitis (grade D) and a stricture located 25 to 40 cm from the incisor teeth. She received medical treatment with fasting and PPIs. The second EGD revealed that the reflux esophagitis had improved somewhat, but that the esophageal stricture had worsened. Thereafter, balloon dilatation was attempted, but the stricture did not improve and she was referred to our hospital. Finally, she was diagnosed as having a benign esophageal stricture caused by reflux esophagitis. She underwent a thoracoscopic esophagectomy with gastric tube reconstruction through the antethoracic route. Her postoperative course was uneventful. Pathologically, a circumferential stricture with white scar formation and no malignant cells were observed. Conclusions We experienced a rare case requiring esophagectomy for long-segment stenosis caused by reflux esophagitis. It is suggested that the possibility of esophageal stricture needs to be kept in mind when treating GERD patients with long-term nasogastric tube placement.

A 55-year-old woman experienced gastrointestinal dysfunction caused by scleroderma. An initial endoscopy revealed an erosive lesion in a long segment of Barrett's esophagus, and a biopsy led to a diagnosis of ectopic gastric mucosa. Two years later, an irregular, elevated tumor developed at the same site. This tumor was suspected of having invaded the submucosal layer. A second biopsy led to a diagnosis of adenocarcinoma. The patient subsequently underwent a thoracoscopic esophagectomy. The resected specimen revealed an invasive tumor front that had invaded the deep layer of a duplicated muscularis mucosae. Intraepithelial neoplasia partially surrounded the tumor. This lesion was thought to have developed into an adenocarcinoma according to the orderly sequence of metaplasia, intraepithelial neoplasia and finally adenocarcinoma over a 2-year period. The present case suggests that erosive lesions in Barrett's esophagus should be strictly followed up by endoscopy, even if a biopsy does not reveal any neoplastic findings.

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.

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.

Prognostic factors for superficial esophageal cancer cannot be limited to such factors as lymph node metastasis (N factor), depth of tumor invasion (T factor), and genetic alterations. The purpose of this study was to examine whether invasive growth patterns of tumors, such as infiltrative growth pattern c (INFc) and budding, represent new useful prognostic factors for superficial esophageal cancer.We investigated 87 cases of superficial esophageal cancer in patients treated with radical surgery. First, the invasive growth pattern of the tumor was pathologically evaluated based on the traditional infiltrative growth pattern (INF) classification. Next, new INF criteria were proposed, and the invasive pattern was re-evaluated. We also investigated budding (Bud) in the stroma of the invasive frontal lesion.When the patients were divided into two groups, with and without an INFc component, the group with an INFc component had a poorer outcome than the group without an INFc component. When the group with an INFc component was defined as "new INFc", new INFc was correlated with the T factor (p = 0.006) and the ly factor (lymphatic invasion) (p = 0.041). Bud was correlated with the T factor (p = 0.001), the N factor (p = 0.030), and new INFc (p0.001). An analysis of survival revealed new INFc (p = 0.002) and Bud (p = 0.006) to be prognostic factors. The survival of the group with new INFc(+)/Bud(+) was poorer than that with new INFc(-)/Bud(-) (p = 0.007).New INFc and Bud, which represent new invasive patterns, were prognostic factors for superficial esophageal cancer.

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.

Background The purpose of this study was to clarify the long-term and short-term outcomes of consecutive patients who underwent thoracoscopic esophagectomy in prone position using a preceding anterior approach for the resection of esophageal cancer at a single institution. Methods We retrospectively reviewed a database of 690 patients with thoracic esophageal cancer who had undergone a thoracoscopic esophagectomy (TE, 351 patients) or an esophagectomy through thoracotomy (OE, 343 patients) between 2003 and 2017. To compare the long-term outcomes of TE and OE, we used a propensity score matching analysis and a Kaplan-Meier survival analysis. To analyze the short-term outcomes of TE, patients were chronologically divided into three groups (117 patients per group). As for thoracoscopic procedure, the esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The intraoperative factors, the number of dissected lymph nodes, and the incidence of adverse events were compared among the three period groups. Results As for long term outcome, 203 patients from each group, for a total of 406 patients, were completely selected and paired. The 5-year survival of the TE patients (66.8%) was better than that of the OE patients (56.4%) (P = 0.044). The thoracoscopic times were 226 min, 241 min, and 214 min (P Conclusion The long-term outcome of TE patients might be better than that of OE patients. As for the short-term outcomes, intraoperative factors, quality of lymph node dissection, and reduction of adverse events were best in the third period group. Establishment of standard procedure and accumulation of surgical cases seemed to make TE a safe and effective procedure for esophageal cancer. Disclosure All authors have declared no conflicts of interest.