Search

We report the use of indocyanine green (ICG) fluorescence for intraoperative diagnosis in two cases of strangulated ileus. We successfully preserved the bowel and avoided postoperative complications by detecting adequate perfusion and no necrosis in the intestine's strangulated regions. In the first case, enhanced computed tomography (CT) revealed a closed loop intestine, which showed poor contrast, and we performed laparotomy with ICG fluorescence. In the second case, the CT scan revealed bowel obstruction without ascites. We conservatively treated the patient with the insertion of a long tube. The patient's condition did not improve, and we performed laparotomy using ICG fluorescence. In both of these cases, the visual observation during laparotomy showed that the ileum had dark-red discoloration. We demonstrated perfusion and preserved the ileum by injecting 2.5 mg of ICG intravenously; fluorescence was observed in the dark-red ileum using the PINPOINT system (Novadaq, Kalamazoo, MI, US). Both patients recovered successfully after the surgery with no adverse events. Our data suggest that ICG fluorescence imaging can be one of the decision-making modalities in patients with strangulated ileus.

At the beginning of the COVID-19 pandemic in 2020, many hospitals around the world recommended stopping elective surgery as a precaution to stop the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The number of elective surgeries was reduced in Japan due to several waves of the pandemic. This work describes the management of COVID-19 and actual polymerase chain reaction (PCR) screening in operating theaters at the National Center for Global Health and Medicine (NCGM), a designated hospital for specified infectious diseases in Japan. The following three steps for COVID-19 infection control were taken to maintain the operating theater: i) Do not bring COVID-19 into the operating theater, ii) Infection control for all medical staff, and iii) Surgical management of surgical patients with COVID-19. We introduced checklists for surgical patients, simulations of surgery on infected patients, screening PCR tests for all surgical patients, and use of a negative pressure room for infective or suspected cases. We determined the flow and timing of surgery for patients with COVID-19. However, many aspects of COVID-19 infection control measures in the operating theater are still unclear. Therefore, infection control measures require further advances in the future to manage new infections.

Preoperative dental cleaning and treatment are increasingly performed as part of perioperative management, and postoperative pneumonia has been reported to be reduced by these dental interventions in patients with esophageal cancer. However, few studies have surveyed the impact of dentition on postoperative sputum culture and pneumonia. Fifty-five consecutive patients who underwent subtotal esophagectomy at Center Hospital of the National Center for Global Health and Medicine between November 2015 and August 2020 were included. Salvage cases, two-stage procedures, and cases with inadequate dental findings were excluded. The number of lost teeth was investigated, and the relationship between sputum surveillance cultures collected on the first to fourth day after surgery and the development of postoperative pneumonia was analyzed. Postoperative sputum surveillance culture revealed pathogenic organisms in 31 (56%) patients. Candida species/P. aeruginosa/Klebsiella species/E. cloacae/S. maltophilia/S. pneumoniae/S. aureus were detected in 27/13/9/7/5/4/4/4%, respectively. Pathogenic organisms were detected significantly more frequently in cases with more than ten lost teeth (p Twelve patients (22%) had postoperative pneumonia with Clavien-Dindo grade 2 or higher. Postoperative pneumonia occurred significantly more frequently in patients with more than ten lost teeth (p=0.03, odds ratio 4.62, 95% CI 1.20-17.8). Postoperative pneumonia occurred significantly more frequently in patients in whom pathogens were detected (p=0.046, odds ratio 5.75, 95% CI 1.12-29.4). Patients with many lost teeth tended to have pathogens detected in early postoperative surveillance cultures before the onset of pneumonia and have more risk of developing postoperative pneumonia.

Risk of anastomotic leakage after esophagectomy is reported comorbidity, surgical technique, and others. One of management to reduce AL is to measure indocyanine green (ICG) of gastric conduit. It may be more sensitive and useful than traditional method. Furthermore, by changing the anastomotic technique with modified Collard method, AL rate was reduced from 15% to 4% and anastomotic stenosis was also reduced. In this study, we examined some marker of stomach roll depiction by ICG. We enrolled 52 cases for which ICG data were obtained from August 2019 to December 2021. The distance from stump of the stomach roll was measured by marking the line ICG 5mg stained after 30, 60 seconds We examined some data of arterial network between left and right gastroepiploic arteries, the depiction of gastric conduit, and intra andextramural vessels from the wall from the recorded images. We decided anastomotic line stained with ICG in 30 second. We reconstructed gastric conduit with 42 stomach roll and 10 subtotal stomach. The distance of gastric conduit stained with ICG was Mean ± SD: 47 ± 19 mm (0-80 mm) at 30 seconds and 28 ± 17 mm (0-60 mm) at 60 seconds. Arterial network between left and right gastroepiploic artery: yes/no (8:43), whole gastric wall depiction: yes/no (24/28), extramural blood flow: yes/no (44/7). There was no necrosis of gastric conduit, AL rate was 3.8% (2/52), and anastomotic stenosis requiring endoscopic bougie was 2%. Ten cases of subtotal stomach had no AL and stenosis. By using ICG, anastomotic line drawn in 30 second was shorter than 60 seconds and gastric conduit was shorter than traditional line. Determining good blood flow sites using ICG in gastric conduit and widening anastomotic caliber using modified Collard method may have reduced AL and stenosis. It is considered to be very simple procedure that does not depend on surgeon.

Background: It is important to check for secondary cancer after esophagectomy. Especially, radiation or chemotherapy for recurrent esophageal cancer, were often performed, and it may be difficult to select treatment for metachronous cancer. We report a case of surgical resection for metachronous cervical esophageal cancer after 7 years for thoracic esophageal cancer with multidisciplinary treatment. Method: A 73-year-old woman underwent right thoracotomy and intrathoracic anastomosis before preoperative chemotherapy for lower thoracic esophageal cancer cT3N3M1 (LN104R) 7 years ago. Final pathological finding was UICC-pT3N3M1 and postoperative additional irradiation was performed. Fifteen months after surgery, there was recurrence of LN112AoP, and definitive chemoradiation therapy was performed. The lesion maintained complete response. Seven years later, upper gastrointestinal endoscopy revealed residual cervical esophageal cancer, and the diagnosis was cT1b (SM) N0M0. Result: Since re-CRT was difficult because of history of irradiation and CRT, we selected surgical cervical esophagectomy without thoracotomy. After partial excision of sternum to widen the view of the upper mediastinum, bilateral laryngeal recurrent nerves were preserved, and trachea and cervical esophagus were exposed. We resected cervical esophagectomy and reconstructed by pedicled jejunum with microvascular anastomosis. The stump of gastric conduit in the thoracic cavity was closed. The final pathology was UICC-pT1bN0M0. Conclusion: There are some cases in which long-term survival can be obtained even for advanced esophageal cancer. It is important to check for secondary cancer after esophagectomy. Radiation therapy and chemotherapy are often used for recurrence of esophageal cancer. We experienced surgical resection for metachronous cervical esophageal cancer 7 years after multidisciplinary treatment for esophageal cancer.

The most common treatment for advanced gastric cancer (AGC) is systemic chemotherapy. The standard treatment for advanced gastric cancer differs worldwide. In Japan, two phase III clinical trials demonstrated the non-inferiority of S-1 compared with 5-fluorouracil (5-FU) and superiority of cisplatin plus S-1 (CS), compared with S-1, with respect to overall survival (SPIRITS trial). Oxaliplatin (L-OHP) has a favorable toxicity profile compared with cisplatin; hence, a phase III clinical trial (G-SOX trial) demonstrated the progression-free survival (PFS) and overall survival in CS was 5.4 and 13.1 months and those in SOX was 5.5 and 14.1 months, respectively. Serious adverse events were more frequently seen in CS than in SOX. So, SOX is as effective as CS for advanced gastric cancer with favorable safety profile. After the publication of this G-SOX trial, the combination of oral or intravenous 5-FU and various doses of L-OHP have been reported. And FOLFOX6 regimen (FOLFOX: a combination of 1-LV and FU with L-OHP) was approved for the treatment of AGC in Japan in 2017. FOLFOX was promising for patients with severe peritoneal metastasis from AGC, because the FOLFOX regimen does not require hydration and does not include oral agents. This review summarizes the efficacy and safety of doublet combinations of platinum and fluoropyrimidines using L-OHP for advanced gastric cancer.

A previous study conducted a transcriptome analysis of paired normal and esophageal squamous cell carcinoma (ESCC) tissue samples. The results showed that the expression of serine protease 27 (PRSS27) was perturbed in tumor samples. Hence, this retrospective study aimed to validate the prognostic significance of PRSS27 in patients with preoperative treatment for ESCC. We enrolled 86 patients who received preoperative treatment before esophagectomy for ESCC. The expression of PRSS27 in resected ESCC and biopsy tissue samples obtained before preoperative treatment was evaluated via immunostaining, and its relationship with clinicopathological features and prognosis was analyzed. In normal esophageal mucosa tissue samples, PRSS27 was expressed in the cytoplasm of spinous cells in the suprabasal layer and basal cells in the basal layer. Of 64 resected ESCC tissue samples, 35 (54.7%) expressed PRSS27 and 29 (45.3%) did not. Moreover, ectopic nuclear expression of PRSS27 was observed. Based on multivariate analysis, PRSS27 expression in resected tumor samples was a predictor of poor prognosis. In cases in which PRSS27 expression was observed in biopsy samples, patients with PRSS27-negative resected tumors had a better postoperative prognosis than those with PRSS27-positive resected tumors. PRSS27 expression in resected ESCC tissue samples is a poor prognostic factor in ESCC patients with preoperative treatment. Furthermore, conversion of PRSS27 expression from positive in biopsy samples to negative in resected tumor samples is a predictor of good prognosis in these patients. Hence, PRSS27 status is an effective tool for decision making regarding adjuvant treatment in ESCC patients.

Hepatectomy for gastric cancer liver metastases (GCLM) has a 5-year survival rate of 9-42%; however, indications for hepatectomy remain unclear. Many researchers have reported prognostic factors for GCLM after hepatectomy, but surgical indications vary according to the literature. Furthermore, the indication for optimal candidates for neoadjuvant chemotherapy and intensive chemotherapy is also unclear. To understand the indications for surgery and chemotherapy intended for hepatectomy for GCLM, a new treatment algorithm was created based on previously reported evidence from the viewpoint of hepatic surgeons.

Definitive chemoradiation (dCRT) is the mainstay treatment for cStage IVa esophageal squamous cell carcinoma (ESCC) with good performance status (PS), according to standard practice guidelines. Salvage surgery may incur operation complications and risk of mortality. According to the esophageal cancer practice guidelines outlined by the Japan Esophageal Society, when a tumor is residual and recurrent, chemotherapy and palliative symptomatic treatment is continued. However, salvage operation has been selected as a therapeutic option for recurrent or residual tumors after dCRT. There is weak evidence for not recommending surgery for cStage IVa ESCC exhibiting residual disease following dCRT. It has been reported that during salvage surgery the only prognostic factor that is thought to be performed is complete resection (R0), but at the same time, salvage esophagectomy increases the incidence of postoperative complications and mortality. The phase II chemoselection study by Yokota T et al. in Japan showed that multidisciplinary treatment initiated by induction therapy, in which docetaxel is added to cisplatin and 5-fluorouracil, resulted in a good prognosis in the short term. In this review, we discuss the surgical strategy and future of unresectable clinical T4 (cT4) ESCC.

Chylothorax is a relatively rare complication of esophagectomy but can lead to fatal conditions. The aim of this report was to present a case of lymphangiography from the para-aortic lymph node (PALN) under computed tomography (CT) guidance, which could be an alternative modality to ultrasound sonography from the groin. A 58-year-old man was diagnosed as having postoperative chylothorax after esophagectomy following neoadjuvant chemotherapy. As the pleural effusion did not improve, intranodal lipiodol lymphangiography from the inguinal lymph node was performed but was unsuccessful. Therefore, CT-guided lymphangiography from the left PALN was performed, and the pleural effusion drainage significantly disappeared. CT-guided lipiodol lymphangiography from the PALN for chylothorax after esophagectomy was safe and thus can be considered an alternative treatment option to ultrasonography-guided intranodal lymphangiography. The flexible use of CT and ultrasonography for lymphangiography may improve the treatment outcomes of chylothorax after esophagectomy.

Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and β-catenin at the cell–cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of β-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2′-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.

4′-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer used for cell proliferation imaging. The aim of this study was to evaluate the prediction of prognosis with pretreatment 4DST PET/CT compared to fluorodeoxyglucose (FDG) PET/CT in patients with esophageal cancer. In this prospective study, we analyzed 46 patients (68.2 ± 10.0 years old) with pathologically proven esophageal squamous cell cancer who underwent pretreatment 4DST and FDG PET/CT. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion proliferation (TLP) were measured for FDG and 4DST PET. The study endpoints were progression-free survival (PFS) and overall survival (OS). Patients’ clinical backgrounds, including age, histological type, clinical stage, and surgical treatment, were adjusted using the Cox proportional-hazards model. In the follow-up period (median 18.8 (interquartile range: 10.1–29.0) months), 26 and 19 patients showed disease progression and cancer-related death, respectively. After adjusting for clinical variables, only the 4DST parameters (SUVmax (p = 0.001) and TLP (p = 0.022)) were statistically significant for predicting PFS. FDG MTV (p = 0.031), 4DST SUVmax (p = 0.022), and TLP (p = 0.023) were statistically significant for predicting OS. Of the PET parameters, 4DST SUVmax yielded the highest adjusted hazard ratio for both PFS (4.88, 95% confidence intervals (CI): 1.83–12.97) and OS (4.19, 95% CI: 1.23–14.20). Higher accumulation of 4DST in the primary tumor may lead to shorter OS and PFS. 4DST PET/CT is useful for predicting prognosis and may outperform FDG PET/CT.

Geriatric patients often have cognitive decline which might cause postoperative complications, including delirium, therefore, it is very important to evaluate mental ability before surgery. The Flemish version of the triage Risk Screening Tool (fTRST), which focuses on the assessment of cognitive function, is reported to be useful for identifying patients with geriatric risks. The aim of our study is to predict postoperative delirium easily in geriatric patients with esophageal cancer (EC). Methods Patients aged ≥70 years old with EC were retrospectively included who received an operation at National Center for Global Health and Medicine from February 2016 to November 2019. The fTRST were administered to all patients. To evaluate objectively, Yamaguchi University Mental Disorder Scale (YDS), one of the famous exams to assess the patient’s cognitive function, were also performed. The impaired were defined as fTRST ≥2 and YDS ≤ 12. We evaluated postoperative delirium and compared the fTRST with YDS. Results Overall, 40 patients were included. Median age was 76 years (range, 70 to 89 years), and 37 patients (85%) were male. Twenty-three patients (58%) were fTRST impaired, 6 patients (15%) were YDS impaired. 21 patients (52%) had postoperative delirium. The abnormal fTRST (p = 0.001) and YDS (p = 0.02) were both at risk for postoperative delirium. In multivariable analysis, the abnormal fTRST was significantly associated with postoperative delirium (OR 5.96; CI 1.33–26.7, p = 0.02). Conclusion The fTRST is useful tools to predict postoperative delirium and prior to YDS in elderly patients with EC. Further studies are needed to design interventions to prevent postoperative delirium for those vulnerable patients.

Esophageal squamous cell carcinoma (ESCC) is associated with the accumulation of genetic and epigenetic changes in the background mucosa. Dysregulated DNA methylation is known to lead to the inactivation of tumor suppressor genes and the activation of oncogenes. To identify the genes whose expression is perturbed by abnormal DNA methylation in ESCC, integrative transcriptomics by serial analysis of gene expression (SAGE) and methylome sequencing by methyl-DNA immunoprecipitation (MeDIP) analysis were performed. We found 159 genes with significantly decreased expression in ESCC compared to that in noncancerous esophageal mucosa. MeDIP-seq analysis identified hypermethylation in the promoter region of 56 of these genes. Using surgically resected tissues of 40 cases, we confirmed that the paired-like homeodomain 1 (PITX1) gene was hypermethylated in ESCC compared to that in normal tissues (P < 0.0001) by pyrosequencing. PITX1 overexpression in ESCC cell lines inhibited cell growth and colony formation, whereas PITX1 knockdown accelerated cell growth. A PITX1-transfected ESCC cell line, KYSE30, formed smaller tumors in nude mice than in mock-transfected cells. Hypermethylation of PITX1 was associated with tumor depth (P = 0.0011) and advanced tumor stage (P = 0.0052) and predicted poor survival in ESCC (hazard ratio, 0.1538; 95% confidence interval, 0.03159–0.7488; P = 0.0169). In this study, we found a novel tumor suppressor gene of ESCC, PITX1, which is silenced by DNA hypermethylation. Downregulation of PITX1 contributes to the growth and progression of ESCC. Hypermethylation of the PITX1 in ESCC correlated with tumor progression and advanced stage cancer, and may predict a poor prognosis.

Background & Aim E-cadherin is a member of the cadherin family and plays a major role in cell–cell adhesion of normal epithelium. Decreased or lack of E-cadherin expression has been reported in breast, colon and bladder cancer, and the disruption of the E-cadherin-mediated cell–cell adhesion is considered the first crucial step of metastasis. The esophageal stratified epithelial cells have many spines that intermingle with each other through desmosomes, in which E-cadherins play an important role for cell–cell adhesion. However, the significance of E-cadherin expression in the progression of esophageal squamous cell carcinoma (ESCC) still remains to be clarified. In the present study, we investigated the relation between E-cadherin expression in tumors and the clinicopathological features of ESCC. Method E-cadherin expression was evaluated in ESCC specimens of 61 patients who underwent surgery from April 2008 to December 2015 at the National Center for Global Health and Medicine by immunohistochemical staining. Distribution of E-cadherin in cancerous tissues was classified as Preserved (expression in cell membrane alone) or Disturbed (expression in cytoplasm or decreased/lack of expression of E-cadherin). Significance of the distribution pattern was analyzed by comparison to clinicopathological features. Results Thirty-seven of 61 (61%) cases revealed Preserved expression pattern while Disturbed distribution was observed in 24 of 61 (39%) cases. Compared to Preserved pattern, Disturbed expression of E-cadherin in tumors was significantly associated with advanced TNM stages (P=0.0462). Conclusion E-cadherin was expressed in most cases of ESCC; however, its distribution was not restricted in membrane but in the cytoplasm of tumors. Disturbed expression of E-cadherin in tumors correlated with advanced stage of ESCC, suggesting that the disruption of the E-cadherin-mediated cell–cell adhesion may play an important role in the progression of ESCC.

Highlights • The treatment for aortogastric tube fistula with active infection is challenging. • The patient developed aortogastric tube fistula after lower esophagectomy. • Repetitive surgical approach allowed hemodynamic and infection control. • There had been no recurrence of esophageal cancer and stent issues for 22 years., Introduction Aortogastric tube fistula is a rare and fatal complication of esophagectomy. The treatment for aortogastric tube fistula with active infection is challenging, wherein a contamination around the fistula can cause a high risk of aneurysm and recurrence of bleeding, even if large amount of bleeding is controlled immediately. Presentation of case We present a case of a 54-year-old male patient who underwent lower esophagectomy for esophageal squamous cell carcinoma 22 years ago. He developed aortogastric tube fistula on postoperative day 46. The patient underwent two surgeries and stenting for aortogastric tube fistula and pseudoaneurysm between days 46 and 120 following the first surgery, and digestive reconstruction was performed 6 months after the first surgery. Computed tomography and esophagogastroduodenoscopy were performed periodically, and the postoperative course was uneventful for 22 years. However, the patient died from pneumonia at the age of 76 years. Autopsy findings revealed no recurrence of esophageal cancer, anastomotic complications, or stent issues. The fistula between the aorta and gastric tube was closed with a stent and connective tissue. Intrathoracic findings revealed that the cause of death was severe bilateral pneumonia. Discussion Immediate hemodynamics stabilization and interval infection control enabled successful disease management. Conclusion Tenting for aneurysm was performed under aseptic conditions, and the patient did not experience recurrence of esophageal cancer and stent issues, which contributed to the long-term survival of 22 years.

Standard gastrectomy with lymphadenectomy is recommended following endoscopic submucosal dissection (ESD) due to the risk of lymph-node metastasis for resected cancers. However, when lymphatic flows remain unchanged after ESD, a minimally invasive function-preserving surgery based on the sentinel node (SN) concept may be applicable. In this study, using porcine survival models, we aimed to investigate whether gastric lymphatic flows were modified following ESD. Twelve pigs, each with one simulating lesion 3 cm in size, were used. Indocyanine green (ICG) fluid was endoscopically injected into the submucosa in four quadrants surrounding the lesion. Following laparoscopic observation of lymphatic flows, the lesions were resected by ESD. After 4 weeks, ICG fluid was injected in four quadrants surrounding the scar and lymphatic flows were observed in the same manner as the initial procedure. The distribution of lymphatic flows, including stained SNs, was compared. In ten lesions (83.3%), the distribution of flows remained unchanged. However, in one lesion, the flow along the right gastric epiploic artery (R-GEA) disappeared on the lesser curvature of the middle stomach. In addition, in one lesion, the flow along R-GEA emerged on the lesser curvature of the lower stomach. Our study revealed that, despite ESD, lymphatic flows remained unchanged in most parts of the stomach. The SN concept may be applied after ESD, except for lesions on the lesser curvature. However, in the case of the lesser curvature, special care must be given to the SN concept.

Surgery for esophageal carcinoma is known to be associated with high morbidity. Recent studies have reported a correlation of nutritional and inflammatory parameters with postoperative course. This study aims to clarify the risk factors for operative morbidity after resection of esophageal carcinoma. Consecutive patients who underwent esophagectomy for esophageal squamous cell carcinoma at our institute were included (n = 102; 89 males and 13 females; mean age: 67.3 years). Clinicopathological characteristics, presence or absence of sarcopenia, and modified Glasgow prognostic score were assessed, and their correlation with postoperative complications was investigated using univariate and multivariate analyses. Sarcopenia was defined using a combination of muscle mass area and body mass index. Of the included 102 patients, 45 (44.1%) exhibited sarcopenia (sarcopenia group), while 57 (55.9%) did not (non-sarcopenia group). No significant difference was observed between the groups regarding surgical procedures and tumor stage; furthermore, there was no mortality. Twenty-six patients developed respiratory complications (including 20 cases of pneumonia). On univariate analysis, sarcopenia, modified Glasgow prognostic score, and American Society of Anesthesiologists physical status were found to be significantly associated with the development of postoperative respiratory complications. On multivariate analysis, sarcopenia was found to be an independent risk factor for postoperative respiratory complications after esophagectomy. We believe that identifying patients at risk and providing preoperative nutritional support as well as physical therapy aimed at strengthening of body muscles may help reduce the incidence of postoperative respiratory complications in such patients.

In the original publication of the article, Fig. 1 was published incorrectly.

We previously conducted transcriptome analysis of a paired specimen of normal and esophageal squamous cell carcinoma (ESCC) tissues and found that mRNA expression of cystatin A (CSTA), a member of the cystatin superfamily, was perturbed in tumors compared with that in the background mucosa. However, little is known about the significance of CSTA expression in ESCC. The mRNA expression of CSTA was evaluated by qRT-PCR using 28 paired frozen samples of tumor and nontumor mucosae. The protein expression of CSTA was evaluated by the immunostaining of formalin-fixed, paraffin-embedded sections of ESCC samples from 59 patients who underwent surgery, and its relationship with clinical features was analyzed. The mRNA expression of CSTA was significantly decreased in ESCC compared with that in matched normal mucosa (P

Our previous differential transcriptome analysis between a paired specimen of normal and esophageal squamous cell carcinoma (ESCC) tissues found aberrant expression of kallikrein-related peptidase 13 (KLK13) in tumors. In this study, we evaluated the expression of KLK13 in many ESCC cases in relation with clinical features, and the prognosis. Eighty-eight ESCC cases were subjected to immunohistological staining for KLK13 and classified into KLK13-negative and KLK13-positive groups. Difference of clinical features and the prognosis between the groups was analyzed. In normal esophageal mucosa, KLK13 expression was evident but limited in the stratum granulosum in all cases. By contrast, only 27 of 88 ESCC samples showed KLK13 expression, whereas the remaining 61 tumors showed no KLK13 expression. The KLK13-positive group was significantly associated with pT classification (deeper tumor invasions; P = 0.0282), pN classification (lymph node metastasis; P = 0.0163), and advanced TNM stage (P = 0.0198). In KLK13-positive samples, KLK13-expressing cells often expressed Ki67, a proliferation marker, unlike normal mucosa, in which Ki67-expressing cells were limited to the basal layer and did not express KLK13. Compared with patients with KLK13-negative group, KLK13-positive group showed poorer postoperative prognosis. Relatively high levels of KLK13 expression in ESCC were associated with cell proliferation and correlated with tumor progression, advanced cancer stage, and poor prognosis.

Background Peptic ulcer occurring in the gastric tube after esophagectomy sometimes penetrates into the mediastinal structures. We reported a case of sternal penetration of gastric tube ulcer successfully treated. Methods A CASE REPORT: Results A 73-years-old man who had undergone video-assisted thracoscopic esophagectomy (VATS) with 3-field lymphadenectomy reconstructed by retrosternal route after neoadjuvant chemo-radiation therapy. He visited outpatient complaining mild pain and redness of skin on anterior chest wall after 7 months of esophagectomy. Computed tomography (CT) revealed gastric tube ulcer penetrated into sternum. Upper GI endoscopy showed active ulcer in lower gastric tube. Biopsy was confirmed no malignant cell but bone tissues. He was admitted and started medication of proton pomp inhibiter and nutritional therapy. After 1 month he was improved symptoms and endoscopic findings. Conclusion There was a rare case of penetration into sternum due to gastric tube ulcer. In the literatures, 4 cases were reported about penetration into sternum. All four cases had symptoms of pain and redness of skin and were diagnosed with upper GI endoscopy and CT. Two cases underwent surgery and another cases were treated conservational therapy. Disclosure All authors have declared no conflicts of interest.

Background Our previous report showed that periplakin (PPL), a member of the plakin family of proteins, was expressed in all the normal esophageal squamous cells, except the Ki67 + basal cell layer; however, PPL-negative cells were observed in esophageal squamous cell carcinoma (ESCC) tissue samples and the proportion of PPL-positive areas in tumors showed considerable variation. In this study, we analyzed the relationships between PPL expression in tumors and the clinicopathological features of ESCC. Methods PPL expression was evaluated by immunostaining ESCC samples from 70 patients who underwent surgery and we classi ed the samples into PPL-negative and PPL-positive groups based on the proportion of PPL-positive areas in tumors, and the relationships among PPL expression, clinical features, and the ESCC prognosis were analyzed. ESCC cell line KYSE270 cells were stably transfected with the PPL expression vector and their growth was assessed by colony formation assay and subcutaneous xenografts in athymic mice. Results As found in our previous study, decreased PPL staining intensity was observed in all of the cancer tissues analyzed, compared with that observed in paired normal esophageal mucosae; however, the PPL-positive group (the percentage of PPL-positive tumor cells was > 20% on immunostaining) exhibited positive associations with the pT classi cation (larger primary tumor) (P = 0.029), pN classi cation (lymph node metastasis) (P = 0.0462), and advanced stages of cancer (P = 0.0253). High PPL expression was observed in all of 26 lymph node metastases analyzed. Furthermore, patients with PPL-positive tumors showed poor postoperative prognosis compared to those with PPL-negative ones. Forced expression of PPL in the KYSE270 ESCC cell line induced a strati ed structure and colony formation. In addition, PPL-transfected cells formed larger tumors in nude mice than mock-transfected cells, suggesting that relatively high PPL expression in tumors may facilitate cell-cell adhesion by desmosome formation and eventual cell growth in vivo. Conclusion PPL expression was generally reduced in ESCC compared with paired non-cancer tissue; however, relatively high levels of PPL expression in tumors correlated with tumor progression, lymph node metastasis, advanced stage cancer, and a poor prognosis. Disclosure All authors have declared no conflicts of interest.

In both advanced and early gastric cancer with preoperatively suspected lymph node metastasis, extended lymph node dissection is needed to achieve R0. Since extended lymph node dissection is difficult to perform laparoscopically, few reports have reported long-term outcomes in large numbers of patients. The purpose of this study was to investigate oncologic outcomes after laparoscopy-assisted distal gastrectomy (LADG) with extended lymph node dissection. Between April 2004 and March 2010, LADG with extended lymph node dissection was performed at our hospital for 880 patients diagnosed with T1N0-1 or T2N0 (N is classified by Japanese topographic classification) gastric cancer in the lower or middle body of the stomach. D2 lymph node dissection was performed for stage IB (T1N1, T2N0) cancers. Modified D2 lymph node dissection was performed for stage IA (T1N0). Overall survival (OS), disease-free survival (DFS), and form of tumor recurrence at 4 years were investigated retrospectively. Median follow-up was 42 months. The 4-year OS was 98.2 % for all patients. By stage, OS/DFS were 99.0/99.0 % in stage IA patients, 95.9/95.9 % in stage IB, 92.6/92.0 % in stage IIA, and 90.0/92.9 % in stage IIB. A total of 11 patients died, including 4 deaths from recurrence (liver metastasis, n = 1; peritoneal dissemination, n = 2; distant lymph node and bone metastases, n = 1). There is 1 patient is alive with recurrence (liver). Mean time until recurrence was 14 months. Oncologic outcomes were good in patients with T1N0-1 and T2N0 gastric cancer who underwent LADG with extended lymph node dissection. This approach appears effective for treating T1N0-1 and T2N0 gastric cancer.

Laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) was introduced as a function-preserving and minimally invasive operation for early gastric cancer (EGC) in Japan. This study investigated the postoperative outcomes, complications, and associated risk factors of the procedure.From January 2005 to December 2009, 307 patients with EGC diagnosed before surgery underwent LAPPG. The postoperative outcomes and complications were assessed in this study. Postoperative complications were classified according to the Clavien-Dindo classification of surgical complications, and risk factors related to complications were analyzed.The mean operation time for LAPPG was 229.4 ± 47.5 minutes and estimated blood loss was 49.1 ± 62.0 mL. The mean total number of dissected lymph nodes was 31.6 ± 10.4, with nodal involvement observed in 25 patients (8.5%). The preoperative diagnostic accuracy of EGC was 93.2%. Complications developed in 53 patients (17.3%), and major complications, classified as grades greater than Clavien-Dindo classification IIIa, were observed in 4 patients (1.3%). The most frequent complication was gastric stasis, occurring in 19 patients (6.2%). Body mass index (BMI) and surgical experience of LAPPG were identified as significant risk factors of postoperative complications. Body mass index was related to severity of the complications. The patients' serum total protein and albumin did not change significantly after surgery.Laparoscopy-assisted pylorus-preserving gastrectomy is a safe operation with excellent postoperative outcomes in terms of minimized major complications based on the Clavien-Dindo classification in patients with EGC in the middle third of the stomach. To prevent postoperative complications, surgeons need to ensure an extra leaning period for LAPPG, and LAPPG should be performed cautiously in patients with high BMI.

Total gastrectomy or proximal gastrectomy is usually performed either as an open procedure or laparoscopically for the treatment of early gastric cancer (EGC) in the upper stomach. However, quality of life after either total or proximal gastrectomy is not so satisfactory. The authors report a novel surgical procedure, laparoscopy-assisted subtotal gastrectomy (LAsTG), by which a very small remnant stomach is preserved, for the surgery of selected EGCs in the upper stomach. Twenty-three patients with EGC in the upper stomach underwent LAsTG. After lymph node dissection and mobilization of the stomach, the stomach was transected about 2 cm proximal to the tumor and a very small remnant stomach was preserved. An anvil was inserted transorally into the remnant stomach by using the OrVil™ system. The reconstruction method was Roux-en-Y, and hemidouble-stapling gastrojejunostomy with a circular stapler was performed intracorporeally. There were no intraoperative complications or conversions to open surgery. Mean operation time and blood loss were 266.7 min and 54.6 ml, respectively. The overall incidence of early postoperative complications was 17.4%, and two patients underwent reoperation because of duodenal stump leakage and stenosis of the Y-anastomosis, respectively. During the follow-up period, two patients experienced gastrojejunostomy stenosis and both were treated successfully by endoscopic balloon dilation. LAsTG may be performed in selected patients with EGC in the upper stomach. With the described method, a very small remnant stomach can be preserved.

Background Epigenetic changes such as DNA methylation are involved in the onset of ESCC. Previously, we have conducted transcriptome and methylome analyses using a paired specimen of ESCC and adjacent non-cancerous tissues and found promotor hypomethylation of NT5E with altered gene expression level in ESCC. NT5E has been known to be an extracellular nucleoside metabolism-related enzyme; however, the significance of its expression in ESCC has never been clarified. In this study, we aimed to evaluate the ESCC-related alteration of the expression of NT5E in using many cases of ESCC. Methods Formalin-fixed, paraffin-embedded sections of surgical specimens from 67 ESCC patients who had undergone esophagectomy or endoscopic submucosal dissection between April 2008 and December 2015 in our hospital were immunostained using anti-NT5E antibody, and classified into NT5E-negative and NE5E-positive groups. To evaluate the mRNA expression of NT5E, qRT-PCR was performed using paired normal and ESCC frozen tissue samples from 24 patients. Results Compared with matched normal mucosa, cancer tissues showed significantly higher NT5E mRNA expression (P Conclusion NT5E gene and protein expression was both upregulated in ESCC; its functional significance in relation to malignancy is underinvestigation. Disclosure All authors have declared no conflicts of interest.

Background An inflammation-based prognostic score, the modified Glasgow Prognostic Score (mGPS), has been established as a useful tool for predicting postoperative outcome in patients with cancer. Recently, depletion of skeletal muscle mass (sarcopenia) has been linked to poor outcome in several types of cancers. In this study investigated the relationship between these factors in patients with operable esopahgeal cancer. Methods Skeletal muscle mass was assessed in 87 patients who underwent esophagectomy from Jan. 2014 to Dec. 2016. The skeletal muscle tissue areas were measured by the ZioStation. The evaluated samples were slices of the third lumbar vertebrae (L3) in the inferior direction. The muscle area normalized by the square of the height (m2) is called the skeletal muscle index (SMI) (cm2/m2). The modified Glasgow prognostic score (mGPS) was measured using C-reactive protein (CRP) and albumin levels (mGPS 2: CRP > 1.0 mg/dL and albumin 1.0 mg/dL; mGPS 0: CRP ≤ 1.0 mg/dL). Patients were given mGPS- L group(mGPS0)or mGPS- H(mGPS1,2). Results The decrease of the skeletal muscle was higher in the mGPS2 than in the mGPS0. The rate of respiratory complications significantly higher in the sarcopenia group than in the non-sarcopenia group (P = 0.01). For other complications the differences were not significant. Kaplan-Meier analysis and log-rank test revealed that Sarcopenia and mGPS-H predicted a higher risk of mortality (P = 0.0034 and 0.0001). Univariate analyses revealed that the mGPS, Stage and Sarcopenia were associated with mortality. Multivariate analyses using these 3 factors revealed that only mGPS (HR: 3.18; 95% CI: 1.70–8.70; P = 0.02) and Sarcopenia (HR: 3.39; 95% CI: 1.27–10.6; P = 0.01) were an independent risk factor of mortality. Conclusion The mGPS was closely related on the progression of sarcopenia, and both the mGPS-H and Sarcopenia were poor prognostic factor respectively. Disclosure All authors have declared no conflicts of interest.

Background Alcohol drinking and smoking are substantial risk factors of esophageal squamous cell carcinoma (ESCC) and are supposed to induce genetic mutations and epigenetic disorders, including aberrant DNA methylation. Previously, we have conducted transcriptome and methylome analyses of a paired specimen of ESCC and adjacent non-cancerous tissues and found that both gene expression and promotor methylation of PRSS27 were perturbed in ESCC. PRSS27 was a trypsin-like serine protease (also known as marapsin) and expressed in normal esophagus; however, little is known about the significance of PRSS27 expression in ESCC. In this study, we evaluated the expression of PRSS27 in many ESCC cases in relation with clinical features and the prognosis. Methods ESCC tissue specimens were obtained from 80 patients who had undergone esophagectomy between April 2008 and December 2016 in our hospital and were subjected to immunostaining for PRSS27. ESCC cases were classified into PRSS27-negative and PRSS27-positive groups and difference of clinical features and the prognosis between the groups was analyzed. Results The mRNA expression of PRSS27 was significantly decreased in ESCC compared with those in matched normal mucosa (P Conclusion PRSS27 gene and protein expression was both downregulated in ESCC; its functional significance in relation to malignancy is underinvestigation. Disclosure All authors have declared no conflicts of interest.

Laparoscopy-assisted distal gastrectomy (LADG) with standard D2 dissection is a complex procedure usually performed only by experienced surgeons, and the feasibility of this procedure still remains unclear.Patients who underwent LADG at the Cancer Institute Hospital between April 2006 and October 2008 were recruited for this study. Early surgical outcomes were compared between patients who underwent complete D2 dissection (complete D2 group; n = 42) and those who underwent D1 + beta dissection (D1 + beta group; n = 179) to determine the feasibility of laparoscopic D2 lymph node dissection.In complete D2 group, the operation time was longer (253 +/- 10 vs 224 +/- 4 min; P = 0.005), and the number of retrieved lymph nodes was larger (41 +/- 2 vs 35 +/- 1; P = 0.002) compared with those in D1 + beta group. The other early surgical outcomes monitored for the two groups were not different between groups.LADG with complete D2 lymph node dissection can be performed safely if the procedure is standardized and an experienced laparoscopic surgeon performs the surgery. To be accepted as a standard treatment for advanced gastric cancer, well-designed prospective trial is necessary.

Laparoscopic gastrectomy (LAG) is increasingly performed to treat gastric cancer. However, the procedure remains complicated, and an optimal system for educating clinicians about LAG has not been established.Our training system centers on understanding the anatomical appearance under laparoscopy and the standardized steps of LAG, including the roles of the scopist and the assistant. The trainees participated in LAG procedures as a scopist and an assistant in 30-35 cases, before conducting their first LAG case. The data of 788 consecutive patients with early gastric cancer who underwent LAG were also reviewed.During the study period, nine trainees performed a total of 215 LAG (27.3 %) with trainers, while 563 LAG were conducted by the two trainers (71.4 %). The surgical outcomes including operative time, blood loss, and retrieval of lymph nodes were almost equivalent for both the trainers and the trainees. The total experience among the trainees as scopist and as first assistant was 45.0 and 41.4 cases, respectively, and the trainees had experienced 33.8 cases as a scopist and 35.3 cases as an assistant before they performed their first LAG as an operator. After commencing experience as an operator, the average operation time of the trainees reached that of the trainers within six cases and their learning curve reached a plateau.Our training system based on attaining sufficient experience as an assistant and scopist in the simulation of a LAG procedure was effective for ensuring clinical safety for LAG performed by a trainee with experienced surgeons.

Laparoscopy-assisted distal gastrectomy (LADG) with extended lymph node dissection has not yet been widely adopted for the treatment of gastric cancers because of the perceived complexity of the procedure. Suprapancreatic lymph node dissection is one of the most important and demanding procedures in this approach. The techniques of duodenal transection within the abdominal cavity or taping of the common hepatic or splenic artery had traditionally been adopted for suprapancreatic nodal dissection during open surgery. In 2005, we developed a new laparoscopic procedure to safely and simply perform suprapancreatic lymph node dissection in LADG. We introduced a left-sided approach for the dissection of lymph nodes in the left gastropancreatic fold, where the body of the stomach is turned over and lifted ventrally to expose the left gastropancreatic fold through the opened lesser sac, without duodenal transection, and the suprapancreatic lymph nodes are resected en bloc in reverse order, i.e., including the lymph nodes along the proximal splenic artery (station 11p), around the celiac artery (station 9), and along the common hepatic artery (station 8a). Between April 2005 and December 2007, a total of 391 patients with cT1,2 gastric cancer underwent this surgical approach. In all patients, surgery was completed safely with favorable outcomes; mean operating time was 239 min and mean blood loss was 63 ml. The complication rate was 4.6% (18/391); there were ten conversions (2.6%) and no mortality. The aim of the present study was to describe the surgical technique of our new approach for LADG with extended lymph node dissection and to evaluate the treatment outcomes achieved by this technique.

Laparoscopy-assisted distal gastrectomy (LADG) has not yet been widely adopted for the treatment of gastric cancers because of the perceived complexity of the procedure. In addition to the proficiency of the operator, other factors could potentially be optimized to improve postoperative outcomes. The aim of this study was to evaluate a standardized operative procedure for assistants performing LADG.Of 114 patients, 64 initially underwent conventional LADG (CLDG) and then 50 underwent standardized procedure (SLDG) in which the role of assistant in LADG was completely established. Parameters compared for the SLDG and CLDG groups were operation time, estimated blood loss, intra- or postoperative complications, preservation of the vagus nerve, and the number of pathologically examined lymph nodes.The operation time for the SLDG procedure (mean +/- SE, 229 +/- 6 min) was shorter than for the CLDG procedure (261 +/- 8 min; P0.002), and the estimated blood loss for SLDG (57 +/- 7 ml) was less than for CLDG (108 +/- 17 ml, P0.004). The celiac branch of the vagus nerve was preserved in 73% of SLDG patients compared with 52% of CLDG patients (P0.03). More lymph nodes were pathologically examined in SLDG patients (38.3 +/- 1.5) than in CLDG patients (32.5 +/- 1.8, P = 0.02).Standardization of the LADG procedure for assistants enabled a shorter operation time, reduced blood loss, a higher rate of vagus nerve preservation, and more accurate lymph node dissection.