True esophagogastric junction adenocarcinoma: background of its definition and current surgical trends.

The definition of true esophagogastric junction (EGJ) adenocarcinoma and its surgical treatment are debatable. We review the basis for the current definition and the Japanese surgical strategy in managing true EGJ adenocarcinoma. The Siewert classification is a well-known anatomical classification system for EGJ adenocarcinomas: type II tumors in the region 1 cm above and 2 cm below the EGJ are described as "true carcinoma of the cardia". Coincidentally, this range matches gastric cardiac gland distribution. Conversely, Nishi's classification is generally used to describe EGJ carcinomas, defined as tumors with the center located within 2 cm above and 2 cm below the EGJ, regardless of their histological subtype. This range coincides with the extent of the lower esophageal sphincter combined with gastric cardiac gland distribution. The current Japanese surgical strategy focuses on the tumor range from the EGJ to the esophagus and stomach. According to previous studies, the strategy can be roughly classified into three types. The optimal surgical procedure for true EGJ adenocarcinoma is controversial. However, an ongoing Japanese nationwide prospective trial will help confirm the appropriate standard surgery, including the optimal extent of lymph node dissection.

Laparoscopic Suprapancreatic Lymph Node Dissection Using a Systematic Mesogastric Excision Concept for Gastric Cancer.

BACKGROUND: Gastrointestinal cancer surgery requires en bloc removal of the primary tumor and organ-specific mesentery1,2. However, this surgical concept for gastric cancer has not yet been applied because of the morphological complexity of the mesenteries of the stomach. Lymph node dissection in gastric cancer surgery can be roughly performed into three regions: lesser curvature, grater curvature, and suprapancreatic region. In this video, we introduced laparoscopic lymphadenectomy in the suprapancreatic region using a systematic mesogastric excision (SME), which has been reported as a concept to perform en bloc resection3. METHODS: This procedure was divided into three steps. First, mesenterization of the mesogastrium was performed by dissecting the embryological planes, and the mesogastrium was dissected from the retroperitoneal surface (Fig. 1a). Second, soft tissue, including the lymph node, was separated from the pancreas and the splenic artery by tracing the inner dissectable layer (Fig. 1b). Finally, the tumor-specific mesentery was transected according to the extent of the lymphadenectomy (Fig. 1c).Fig. 1Intraoperative findings during the stepwise procedure in dissecting the lymph node in the suprapancreatic region. The red broken line indicates the surgical outline. a The mesogastrium is dissected from the retroperitoneal tissue. b The mesogastrium is separated from the pancreas and splenic artery. c The mesogastric transection line is determined on the basis of the extent of the lymphadenectomy. Inf. phrenic a. inferior phrenic artery; PGA posterior gastric artery; Post. epiploic a. posterior epiploic artery; RV renal vein; SA splenic artery; SV splenic vein RESULTS: Between January 2017 and December 2017, six patients underwent laparoscopic distal gastrectomy with D2 lymphadenectomy using SME. The median time required to complete the suprapancreatic lymphadenectomy was 48 min. No patient underwent conversion to open surgery or experienced intraoperative complications. CONCLUSIONS: We believe that this laparoscopic suprapancreatic lymphadenectomy using SME takes advantage of the surgical anatomy and achieves en bloc removal of the primary tumor and gastric mesentery. This series is a proof of concept that this procedure can be performed in a timely manner and is feasible.

Creation of Virtual Three-Dimensional Animation Using Computer Graphic Technology for Videoscopic Transcervical Upper Mediastinal Esophageal Dissection.

Background: Videoscopic transcervical mediastinal lymphadenectomy has been attempted to reduce thoracotomy-related complications of surgical treatment for esophageal cancer. However, many surgeons would hesitate to attempt this procedure because of the difficulty in understanding the anatomical orientation. In this study, we aimed to create a three-dimensional computer graphic (3D CG) animation and compare it with the real-life operation. Materials and Methods: LightWave 3D® version 7 was used as a rendering software to create the 3D CG. The 3D CG images were superimposed to generate an animation using AfterEffects CC®. Results: The 3D CG animation for videoscopic transcervical upper mediastinal esophageal dissection was successfully created; it dynamically shows the scene, especially the separation between the esophagus and trachea, and enables surgeons to easily understand the anatomical orientation when using transcervical approach. This 3D CG animation was of high quality and similar to the real-life operation. Conclusions: We created a virtual 3D CG animation for the transcervical approach, which will contribute to understanding this procedure for esophageal cancer preoperatively.

Laparoscopic modified lymphadenectomy in gastric cancer surgery using systematic mesogastric excision: a novel technique based on a concept.

PURPOSE: Radical surgery for gastrointestinal cancer involves en bloc removal of the primary tumor and organ-specific mesenteries. However, the surgical concept and technique for lymphadenectomy during gastric cancer surgery remain unclear. We examined a novel technique for laparoscopic modified lymphadenectomy during gastric cancer surgery involving systematic mesogastric excision (SME) and focused on the topographic anatomy, surgical technique, and specimens. METHODS: Our surgical technique involved the following: mesenterization by dissociating embryological planes, separating fat tissue containing lymph nodes from the pancreas and its associated vessels by tracing the intramesenteric dissectable layers, and dissecting the lymph node that is dependent on the D1+ criteria. RESULTS: Between October 2011 and September 2016, 227 patients underwent laparoscopic D1+ gastrectomy using SME. Of these, total gastrectomy was performed in 47 cases and distal gastrectomy was performed in 180 cases. The median operative time was 303 min (range, 201-722 min), and estimated blood loss was 50 mL (range, 0-550 mL). The median number of harvested lymph nodes was 54 (range, 18-163). There was no conversion to open surgery. CONCLUSIONS: SME was adapted for modified gastrectomy and is considered safe. Modified lymphadenectomy during gastrectomy is determined by the resection margin of the mesogastrium.

The eCura system as a novel indicator for the necessity of salvage surgery after non-curative ESD for gastric cancer: A case-control study.

Endoscopic submucosal dissection (ESD) for early gastric cancer does not always lead to complete cancer resection. The aim of this study was to determine indicators for cancer residue (CR) status in cases of non-curative ESD. We analyzed 47 cases of non-curative ESD followed by salvage surgery and collected data regarding the rates of CR, which included both local CR and lymph node metastasis (LNM). To elucidate the risk factors for CR status, we compared the CR positive and the CR negative groups among surgical specimens according to the following variables obtained from ESD findings: tumor location, tumor size, depth of invasion, lympho-vascular invasion, histological margin, and histological diagnosis. The eCura system, which is an LNM risk scoring system, was also applied and scores were calculated in each case as follows: 3 points for lymphatic invasion and 1 point each for tumor size >30 mm, positive vertical margin, venous invasion, and submucosal invasion ≥500 µm. There were 9 (19%) CR positive cases, which included 6 cases of local CR and 4 cases of LNM; no cancer was detected in over 80% of the patients. The eCura scoring system was the only significant factor for CR status: the higher the eCura score, the greater the CR positivity (p = 0.0128). In particular, all patients in the low-risk group (score = 0-1 point) had no CR. Although no cancer recurrence was observed during a median follow-up of 4 years, 2 patients died of pneumonia. In conclusion, the eCura system might make it possible to select appropriate cases for salvage surgery.

Efficacy of Endoscopic Management for Early Remnant Gastric Cancer: Is Completion Gastrectomy Truly Necessary in Cases with Marginally Noncurative Histopathologic Features?

BACKGROUND: For patients with early primary gastric cancer, endoscopic management has become a standard of care. However, its efficacy for early remnant gastric cancer (ERGC) remains controversial and an invasive surgical procedure remains the primary choice of treatment. METHODS: A multi-institutional database of ERGC cases was retrospectively reviewed. Efficacy of endoscopic resection was analyzed by reviewing the clinicopathologic features of patients who underwent endoscopic resection and comparing the long-term outcomes with those of surgical resection. RESULTS: Of the 121 patients who were histopathologically diagnosed with ERGC after distal gastrectomy, 80 underwent endoscopic resection and 41 underwent completion gastrectomy (Group S). According to the histopathological criteria, 55 of the 80 endoscopic resection cases were classified as "curative resection" (Group E1) and the remaining 25 were classified as "noncurative resection" (Group E2). Tumor recurrence was observed only in three patients (12%) in Group E2, and no tumor recurrence was confirmed in Group S and Group E1. Multivariate analyses confirmed that completion gastrectomy [hazard ratio (HR), 6.2; 95% confidence interval (CI), 1.5-26.3] was associated with poor survival compared with endoscopic resection, and lymphovascular infiltration (HR 9.5; 95% CI 2.5-36.7) was correlated with tumor recurrence. Histopathological positive resection margin, tumor size, or deeper tumor invasion were not correlated with tumor recurrence after endoscopic resection. CONCLUSIONS: Endoscopic management might be an effective treatment option for ERGC with potential long-term survival advantage over the completion gastrectomy even in cases with histopathological features, suggesting noncurative resection.

[A Case of Stage IV Gastric Cancer Which Showed Pathological Complete Response after Neo-Adjuvant Chemotherapy].

We report a case of Stage IV gastric cancer showing pathological complete response(pCR)after neo-adjuvant chemotherapy( NAC)using S-1 and oxaliplatin(SOX).A woman 73-year-old was diagnosed as harming type 3 Stage IV gastric cancer with para-aortic lymph node(PAN)metastasis.She underwent 4 courses of NAC with SOX regimen.After the treatment, both the primary tumor and the metastatic PAN decreased in size remarkably.She underwent distal gastrectomy with D2 plus PAN dissection with curative intent.Pathological diagnosis revealed complete disappearance of cancer cells in both the primary lesion of the stomach and all dissected lymph nodes, confirming pCR.She is alive without recurrence 4 months after surgery.

Degradation and emission of carbonyl sulfide, an atmospheric trace gas, by fungi isolated from forest soil.

Soil is thought to be important both as a source and a sink of carbonyl sulfide (COS) in the troposphere, but the mechanism affecting COS uptake, especially for fungi, remains uncertain. Fungal isolates that were collected randomly from forest soil showed COS-degrading ability at high frequencies: 38 out of 43 isolates grown on potato dextrose agar showed degradation of 30 ppmv COS within 24 h. Of these isolates, eight degraded 30 ppmv of COS to below the detection limit within 2 h. These isolates also showed an ability to degrade COS included in ambient air (around 500 pptv) and highly concentrated (12 500 ppmv) level, even though the latter is higher than the lethal level for mammals. COS-degrading activity was estimated by using ergosterol as a biomass index for fungi. Trichoderma sp. THIF08 had the highest COS-degrading activity of all the isolates. Interestingly, Umbelopsis/Mortierella spp. THIF09 and THIF13 were unable to degrade 30 ppmv COS within 24 h, and actually emitted COS during the cultivation in ambient air. These results indicate a fungal contribution to the flux of COS between the terrestrial and atmospheric environments.

[Clinical Outcomes of Local Therapy for Lymph Node Recurrence after Radical Esophagectomy for Esophageal Cancer].

We analyzed the prognostic factors related to long-term survival in 31 patients, 27 men and 4 women, median age 67 years, who had lymph node recurrence after radical esophagectomy for esophageal cancer. The pathological Stage was Stage I in 2 patients, Stage II in 9 patients, Stage III in 18 patients, and Stage IV a in 2 patients. Seventeen patients were diagnosed with lymph node recurrence in a single area and the other 14 patients were diagnosed with lymph node recurrence in multiple areas(n=3)or lymph node recurrence complicated by hematogenous or disseminated metastases(n=11). Eighteen patients were treated with chemoradiotherapy(CRT), and surgical intervention after CRT was indicated in 5 of them. One patient had surgery alone, 7 were treated with chemotherapy, and 5 were administered best palliative care. The median survival after recurrence was 357 days. The patients with lymph node recurrence in a single area and those treated by CRT or surgery had significantly better prognosis than the others. Although the overall prognosis for patients with tumor recurrence after esophagectomy is poor, lymph node recurrence in a single area or treated with local therapy was associated with better long-term survival.

[Present state and prospects of adjuvant chemotherapy for gastric cancer].

In Japan, a one-year administration of S-1 is the standard adjuvant treatment for stage II/III gastric cancer after curative gastrectomy with a D2 lymph-node dissection.The treatment is recommended in the Japanese Guidelines for Treatment of Gastric Cancer(3rd Edition).Using data from results of a 5-year follow-up of the ACTS-GC trial, it was confirmed that using S-1 significantly improves the 5-year overall survival over surgery alone.However, the recurrence rate of stage III gastric cancer is still too high.More powerful treatment using multiple drugs is needed for this disease.This paper presents a new perspective for the development of post-operative adjuvant chemotherapy in the future, based on clinical trials recently reported.

Antagonistic roles of Wnt5 and the Drl receptor in patterning the Drosophila antennal lobe.

Numerous studies have shown that ingrowing olfactory axons exert powerful inductive influences on olfactory map development. From an overexpression screen, we have identified wnt5 as a potent organizer of the olfactory map in Drosophila melanogaster. Loss of wnt5 resulted in severe derangement of the glomerular pattern, whereas overexpression of wnt5 resulted in the formation of ectopic midline glomeruli. Cell type-specific cDNA rescue and mosaic experiments showed that wnt5 functions in olfactory neurons. Mutation of the derailed (drl) gene, encoding a receptor for Wnt5, resulted in derangement of the glomerular map, ectopic midline glomeruli and the accumulation of Wnt5 at the midline. We show here that drl functions in glial cells, where it acts upstream of wnt5 to modulate its function in glomerular patterning. Our findings establish wnt5 as an anterograde signal that is expressed by olfactory axons and demonstrate a previously unappreciated, yet powerful, role for glia in patterning the Drosophila olfactory map.

Misexpression screen for genes altering the olfactory map in Drosophila.

Despite the identification of a number of guidance molecules, a comprehensive picture has yet to emerge to explain the precise anatomy of the olfactory map. From a misexpression screen of 1,515 P{GS} lines, we identified 23 genes that, when forcibly expressed in the olfactory receptor neurons, disrupted the stereotyped anatomy of the Drosophila antennal lobes. These genes, which have not been shown previously to control olfactory map development, encode novel proteins as well as proteins with known roles in axonal outgrowth and cytoskeletal remodeling. We analyzed Akap200, which encodes a Protein Kinase A-binding protein. Overexpression of Akap200 resulted in fusion of the glomeruli, while its loss resulted in misshapen and ectopic glomeruli. The requirement of Akap200 validates our screen as an effective approach for recovering genes controlling glomerular map patterning. Our finding of diverse classes of genes reveals the complexity of the mechanisms that underlie olfactory map development.

Lim kinase regulates the development of olfactory and neuromuscular synapses.

Lim Kinase (Limk) belongs to a phylogenetically conserved family of serine/threonine kinases, which have been shown to be potent regulators of the actin cytoskeleton. Despite accumulating evidence of its biochemical actions, its in vivo function has remained poorly understood. The association of the Limk1 gene with Williams Syndrome indicates that proteins of this family play a role in the nervous system. To unravel the cellular and molecular functions of Limk, we have either knocked out or activated the Limk gene in Drosophila. At the neuromuscular junction, loss of Limk leads to enlarged terminals, while increasing the activity of Limk leads to stunted terminals with fewer synaptic boutons. In the antennal lobe, loss of Limk abolishes the ability of p21-activated kinase (Pak) to alter glomerular development. In contrast, increase in Limk function leads to ectopic glomeruli, a phenotype suppressible by the coexpression of a hyperactive Cofilin gene. These results establish Limk as a critical regulator of Cofilin function and synapse development, and a downstream effector of Pak in vivo.