Intraneural fibrosis within ilioinguinal nerve in inguinal hernia patients with preoperative pain: it's the sign of irreversible nerve injury, isn't it?

PURPOSE: Preoperative pain is known as one of the most powerful risk factors for chronic postoperative inguinal pain (CPIP), while its pathogenesis has not been fully elucidated. The aim of the present study was to evaluate patients with preoperative pain from the pathological perspective and discuss the potential pathogenesis of CPIP in those patients. METHODS: This was a single-institutional retrospective study. The study population was inguinal hernia patients with preoperative pain who underwent open anterior hernia repair for primary inguinal hernia with pragmatic ilioinguinal neurectomy during surgery between March 2021 and March 2023. The primary and secondary outcomes were proportion of collagen deposition and mucus accumulation within ilioinguinal nerve in those patients, respectively, which were evaluated histologically using Image J software. RESULTS: Forty patients were evaluated. Median value of proportion of intraneural collagen deposition was 38.3% (27.7-95.9). These values were positively correlated with the duration of pain (r2=0.468, P<0.001). Median value of proportion of mucus accumulation in ilioinguinal nerve was 50.1% (0-82.0). These values had no correlation with any clinicopathological variables. CONCLUSIONS: In the present study population, all patients with preoperative pain had intraneural fibrosis within ilioinguinal nerve, and its degree had a positive correlation with the pain duration.

Anastomosis behind the sternoclavicular joint is associated with increased incidence of anastomotic stenosis in retrosternal reconstruction with a gastric conduit after esophagectomy.

Anastomotic stenosis after esophagectomy is a major cause of long-term morbidity because it leads to poor dietary intake and malnutrition that markedly reduces the quality of life. The aim of this study was to test the hypothesis that anastomosis behind the sternoclavicular (SC) joint in retrosternal reconstruction is associated with an increased risk of anastomotic stenosis compared with anastomosis deviated from the joint. Among 226 patients who underwent esophagectomy for esophageal cancer between April 2010 and March 2019, we selected 114 patients who underwent retrosternal reconstruction using a gastric conduit for this study. They were classified into two groups according to the location of the anastomosis as determined by axial sections on postoperative computed tomography scans: anastomosis located behind the SC joint (Group B; n = 71) and anastomosis deviated from the joint (Group D; n = 43). The primary endpoint was the difference in the incidence of anastomotic stenosis between the two groups. Whether the occurrence of anastomotic leak affected the likelihood of anastomotic stenosis was also investigated. The incidence of anastomotic stenosis was significantly higher in Group B than in Group D (71.8% [n = 51] vs. 18.6% [n = 8]; P < 0.0001). The incidence of stenosis in patients who developed an anastomotic leak was significantly higher in Group B than in Group D (88.0% vs. 41.7%; P = 0.0057), although the findings were similar in patients who did not develop anastomotic leak (63.0% and 9.7%, respectively; P < 0.0001). We conclude that anastomosis located behind the SC joint in retrosternal reconstruction with a gastric conduit after esophagectomy is associated with an increased risk of anastomotic stenosis regardless of the development of anastomotic leak.

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.

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 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.

Novel full-spectral flow cytometry with multiple spectrally-adjacent fluorescent proteins and fluorochromes and visualization of in vivo cellular movement.

Flow cytometric analysis with multicolor fluoroprobes is an essential method for detecting biological signatures of cells. Here, we present a new full-spectral flow cytometer (spectral-FCM). Unlike conventional flow cytometer, this spectral-FCM acquires the emitted fluorescence for all probes across the full-spectrum from each cell with 32 channels sequential PMT unit after dispersion with prism, and extracts the signals of each fluoroprobe based on the spectral shape of each fluoroprobe using unique algorithm in high speed, high sensitive, accurate, automatic and real-time. The spectral-FCM detects the continuous changes in emission spectra from green to red of the photoconvertible protein, KikGR with high-spectral resolution and separates spectrally-adjacent fluoroprobes, such as FITC (Emission peak (Em) 519 nm) and EGFP (Em 507 nm). Moreover, the spectral-FCM can measure and subtract autofluorescence of each cell providing increased signal-to-noise ratios and improved resolution of dim samples, which leads to a transformative technology for investigation of single cell state and function. These advances make it possible to perform 11-color fluorescence analysis to visualize movement of multilinage immune cells by using KikGR-expressing mice. Thus, the novel spectral flow cytometry improves the combinational use of spectrally-adjacent various FPs and multicolor fluorochromes in metabolically active cell for the investigation of not only the immune system but also other research and clinical fields of use.

Port-Site Metastasis After Laparoscopic Gastrectomy Extending to the Thigh: A Case Report.

Port-site metastasis (PSM) is rare following laparoscopic gastrectomy for gastric cancer. Previous reports focused on localized lesions treated with excision; contrastingly, case reports describing extensive invasion into the lower extremity skeletal muscles causing deterioration in activities of daily living are nonexistent. A 55-year-old male underwent a laparoscopic distal gastrectomy for gastric cancer. The pathological findings revealed a stage IIIA tumor. Two years later, skin hardening was observed on the left upper abdominal wall. Computed tomography displayed a 13-cm-long, flat tumor along the skeletal muscle around the left upper 12 mm port site and right hydronephrosis. The patient was diagnosed with PSM and retroperitoneal recurrence. Despite chemotherapy, three years postoperatively, PSM widely spread from the left upper abdomen to the left thigh, eventually inducing opioid-resistant leg pain and subsequent walking difficulties. Palliative radiotherapy could not improve these symptoms. The patient died three years and five months postoperatively. Extensively invasive PSM can induce refractory cancer pain and physical disorders. Therefore, early detection and palliative resection of PSM may help maintain the quality of life of patients with gastric cancer.

Feasibility of Narrow-Spectrum Antimicrobial Agents for Post-Operative Intra-Abdominal Infections After Gastrectomy.

Introduction: Recently, antimicrobial resistance has received considerable attention. Broad-spectrum antimicrobial agents are recommended as the initial therapy for post-operative intra-abdominal infections. However, at our institution, we have adopted a tactic of initially treating post-operative intra-abdominal complications with relatively narrow-spectrum antimicrobial agents, such as second-generation cephalosporins. In the present study, we aimed to retrospectively analyze the use of antimicrobial agents and the resulting treatment outcomes in patients with intra-abdominal complications after gastrectomy at our facility. Methods: We conducted a retrospective observational study of patients treated with antibiotic agents for intra-abdominal infectious complications after gastrectomy between 2011 and 2021. We determined the proportion of "initial treatment failures" associated with the initial administration of antibiotic agents for post-operative intra-abdominal complications. Results: Post-operative intra-abdominal infections were observed in 29 patients. Broad-spectrum antimicrobial agents were not administered. We successfully treated 19 patients. Initial treatment failure was observed in 10 patients, of whom five experienced failure due to bacterial resistance to the initial antimicrobial agent. All 10 patients who experienced initial treatment failure were discharged after drainage procedures or other treatments. There were no deaths due to post-operative complications. Cefmetazole was used as the initial antimicrobial agent in 27 of the 29 patients. Conclusions: Considering that all patients with post-gastrectomy intra-abdominal infections were successfully treated using relatively narrow-spectrum antimicrobial agents, and initial treatment failure due to antimicrobial-resistant pathogens was 17.2%, the use of narrow-range antimicrobial agents for intra-abdominal infections after gastrectomy can be deemed appropriate.

Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report.

Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.

The flow angle beneath the gastrojejunostomy predicts delayed gastric emptying in Roux-en-Y reconstruction after distal gastrectomy.

BACKGROUND: Delayed gastric emptying without mechanical obstruction after Roux-en-Y reconstruction has been defined as Roux stasis syndrome. It occurs in 10-30% of patients after such reconstruction. So far, the cause of this stasis has not been completely identified. This study aimed to reduce Roux stasis using surgical techniques. METHODS: From November 2007 to October 2010, we performed 101 distal gastrectomies with Roux-en-Y reconstruction. All the gastrojejunostomies were performed with end-to-end anastomoses. Roux stasis was analyzed with respect to tumor location, extent of the dissection, tumor progression, operation time, antecolic/retrocolic reconstruction, and the shape of the gastrojejunostomy. The shape of the gastrojejunostomy was evaluated by contrast gastroradiography 4 days after the operation. RESULTS: Roux stasis syndrome was observed in 17 of the 101 patients. There was no relationship between the extent of the dissection, tumor progression, or operation time and the occurrence of Roux stasis. There was no difference in the incidence of Roux stasis between antecolic and retrocolic reconstructions. However, the group that displayed a straight anastomotic shape on contrast radiography demonstrated an apparently lower incidence of Roux stasis (p = 0.0003). In addition, Roux-en-Y reconstruction following gastric cancer was more frequently followed by Roux stasis in the antrum than in the midstomach (p = 0.0036). Cases of Roux stasis occurred 11.8 days after surgery on average and resolved within 2 weeks on average. CONCLUSIONS: Our findings demonstrate the substantial benefits of a straight anastomosis of the gastrojejunostomy for the prevention of Roux stasis syndrome.

Pathological Complete Remission of Liver Metastases Correlates With Elimination of Tumor-infiltrating Tregs in Gastric Cancer.

BACKGROUND/AIM: Tumor-infiltrating Foxp3+ regulatory T-cells (Ti-Tregs) promote tumor progression and contribute to poor prognosis in gastric cancer, but the relationship between Ti-Tregs and response to chemotherapy for liver metastases from gastric cancer (LMGC) is unclear. We estimated the correlation between pathological response to chemotherapy and Ti-Tregs in LMGC. PATIENTS AND METHODS: Ti-Tregs were analyzed with immunohistochemistry as CD3+ Foxp3+ cells in patients with synchronous LMGC. RESULTS: Of 53 patients with LMGC, 49 received chemotherapy as initial treatment and 10 underwent R0 resection. LMGC disappeared pathologically in 5 resected cases despite radiologically residual disease. Ti-Tregs were found frequently in residual LMGC and primary lesions but rarely in tumor scar tissue. There was no relationship between frequency of CD8+ cells and pathological response. CONCLUSION: Marked reduction in Ti-Tregs correlates with pathological complete remission of LMGC. Ti-Tregs may be a biomarker to predict the effects of chemotherapy when used in combination with radiological findings.

Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity.

Immunogenic tumor cell death enhances anti-tumor immunity. However, the mechanisms underlying this effect are incompletely understood. We established a system to induce tumor cell death in situ and investigated its effect on dendritic cell (DC) migration and T cell responses using intravital photolabeling in mice expressing KikGR photoconvertible protein. We demonstrate that tumor cell death induces phagocytosis of tumor cells by tumor-infiltrating (Ti)-DCs, and HMGB1-TLR4 and ATP-P2X7 receptor signaling-dependent Ti-DC emigration to draining lymph nodes (dLNs). This led to an increase in anti-tumor CD8+ T cells of memory precursor effector phenotype and secondary tumor growth inhibition in a CD103+ DC-dependent manner. However, combining tumor cell death induction with lipopolysaccharide treatment stimulated Ti-DC maturation and emigration to dLNs but did not improve tumor immunity. Thus, immunogenic tumor cell death enhances tumor immunity by increasing Ti-DC migration to dLNs where they promote anti-tumor T cell responses and tumor growth inhibition.

Superior lumbar hernia after gastrectomy repaired via an open approach in the prone position: A case report.

INTRODUCTION: Lumbar hernia is a rare hernia in the posterolateral abdominal wall and only about 310 cases are known to have been reported to date. Laparoscopic hernioplasty is a common surgical approach but is unsuitable for patients who have previously undergone laparotomy and are expected to have extensive visceral adhesions. PRESENTATION OF CASE: An 84-year-old woman who had undergone an open distal gastrectomy was referred to our hospital with an enlarging but easily reducible bulge in the right upper back. On computed tomography, the hernial orifice was located in the lateral side of the right quadratus lumborum under the costal arch. The bulge was diagnosed as a superior lumbar hernia. We performed an open hernioplasty in the prone position to avoid internal visceral adhesions. The hernia sac was detected in the latissimus dorsi in the back, and was found to contain the ileocecum, which was rigidly adherent to the sac. Hernioplasty was performed by inserting polypropylene mesh between Zuckerkandl's fascia and the internal oblique. DISCUSSION: Mechanical ileus after open distal gastrectomy is common complication and sometimes position was simple procedure without the influence of visceral adhesion and easily reinforced by underlay mesh. CONCLUSIONS: Open hernioplasty in the prone position using a mesh underlay is an optional approach in a patient with a superior lumbar hernia after gastrectomy.

Endoscopic observation of the palisade vessels in Killian-Jamieson diverticulum was useful for diagnosis and surgical treatment: a case report.

BACKGROUND: Killian-Jamieson diverticulum is a rare pharyngoesophageal diverticulum that arises below the cricopharyngeus muscle. Unlike the most common Zenker's diverticulum, which requires cricopharyngeal and esophageal myotomy, diverticulectomy is sufficient for surgical treatment of Killian-Jamieson diverticulum. Thus, accurate preoperative diagnosis is indispensable for avoiding unnecessarily invasive surgery. Here, we report a case of Killian-Jamieson diverticulum in which endoscopic observation of the palisade vessels was useful for diagnosis and intraoperative endoscopy was effective in guiding surgical resection. CASE PRESENTATION: A 65-year-old woman complained of pharyngeal discomfort and increased coughing and was referred to our hospital with a diagnosis of a pharyngoesophageal diverticulum. Contrast esophagography and cervical computed tomography revealed a diverticulum measuring 3 cm in diameter on the left side of the cervix. The diverticulum was identified by endoscopy just below the palisade vessels, which represents the level of the upper esophageal sphincter, and was diagnosed as Killian-Jamieson diverticulum. She underwent diverticulectomy without cricopharyngeal and esophageal myotomy. After exposing the diverticulum under light from the endoscope and washing out the food residue inside endoscopically, the diverticulum was resected using the endoscope as a bougie so as not to narrow the esophagus. The postoperative course was uneventful, and she remains asymptomatic without recurrence or stenosis at 6 months after surgery. CONCLUSIONS: Endoscopic observation of the palisade vessels in addition to esophagography can help diagnose Killian-Jamieson diverticulum and determine the optimal surgical procedure. Diverticulectomy can be performed intentionally and safely with the aid of intraoperative endoscopy.

Laparoscopic and left thoracoscopic Ivor-Lewis esophagectomy for Siewert type II esophagogastric junction cancer with right aortic arch: a case report.

BACKGROUND: Right aortic arch (RAA) is a congenital malformation detected in 0.04% of the population without heterotaxia and makes esophagectomy and mediastinal lymphadenectomy difficult. A left thoracic approach is recommended in patients with RAA, but a minimally invasive procedure has not yet been established. CASE PRESENTATION: The case was a 40-year-old man with RAA and Siewert type II adenocarcinoma of the esophagogastric junction with metastases to the adrenal glands and paraaortic lymph nodes. Conversion surgery was performed when radiologic disappearance of metastatic disease was confirmed after first-line treatment consisting of 12 cycles of S-1 plus platinum-based systemic chemotherapy. Minimally invasive laparoscopic and left thoracoscopic Ivor-Lewis esophagectomy was performed in the right semi-lateral decubitus position. The esophagus was easy to see on left thoracoscopy because of the RAA. Esophagectomy with lower mediastinal lymphadenectomy and an intrathoracic esophagogastric anastomosis was performed successfully with laparoscopy and thoracoscopy without a position change. There were no surgical complications, and no residual cancer was detected in the resected specimen on pathological examination. There has been no recurrence during 21 months of follow-up. CONCLUSIONS: Laparoscopic and left thoracoscopic Ivor-Lewis esophagectomy in the right semi-lateral decubitus position is a minimally invasive, anatomically novel procedure for Siewert type II esophagogastric junction cancer in patients with RAA.

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.

Functional Phenotypic Diversity of Regulatory T Cells Remaining in Inflamed Skin.

Regulatory T cells (Tregs) migrate between lymphoid and peripheral tissues for maintaining immune homeostasis. Tissue-specific function and functional heterogeneity of Tregs have been suggested, however, correlation between them and inter-tissue movement remain unknown. We used a contact hypersensitivity model of mice expressing a photoconvertible protein for tracking migratory cells. After marking cells in skin, we purified Tregs exhibiting a different migration pattern [Tregs recruiting to or remaining in the skin and emigrating from the skin to draining lymph nodes (dLNs) within half a day] and examined single-cell gene and protein expression profiles. Correlation and unsupervised clustering analyses revealed that Tregs in both skin and dLNs comprised two subpopulations, one highly expressing Nrp1 with variable CD25, Granzyme B, and/or CTLA-4 expression and another with 3 subsets strongly expressing CD25, Granzyme B, or CTLA-4 together with CD39. Characteristic subsets of Tregs remaining in the skin displayed higher CD25 and CD39 expression and lower Granzyme B and CTLA-4 expression compared with Tregs migrating to the skin. In addition, CCR5 expression in Tregs in skin was positively and negatively correlated with CD39 and Nrp-1 expression, respectively. To assess the predictive value of these data for immunotherapy, we blocked CCR5 signaling and found modest downregulation of CD39 and modest upregulation of Nrp1 expression in skin Tregs. Our data reveal a high functional diversity of Tregs in skin that is strongly related to trafficking behavior, particularly skin retention. Modulation of tissue-specific trafficking and function is a promising clinical strategy against autoimmune, infectious, and neoplastic diseases. Significance Statement: Regulatory T cells (Tregs) are essential for maintaining immune homeostasis. To reveal tissue-specific immunoinhibitory functions and inter-tissue movement correlation based on Treg functional heterogeneity, we examined single-cell gene and protein expression profiles of Tregs recruited to, remaining in, or emigrating from the contact hypersensitivity-induced inflamed skin. Tregs in skin were composed of several subpopulations; one with high Nrp1 expression and another with 3 subsets strongly expressing CD25, Granzyme B, or CTLA-4 together with CD39. Tregs remaining in skin displayed highCD25, CD39, and CCR5 expression, and CCR5 signaling blockade downregulated CD39. A high Treg functional diversity in skin is strongly related to trafficking behavior. Tissue-specific trafficking and functional modulation are a promising clinical strategy against autoimmune, infectious, and neoplastic diseases.

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.

A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response.

Foxp3+ regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43+ CCR5+ Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43+ CCR5+ CXCR3- Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.