[Usefulness of an Epidural Catheter with a Subcutaneous Port for Locally Advanced Rectal Cancer Pain Which Was Difficult to Manage with Opioids-A Case Report].

A 56-year-old woman was diagnosed with advanced rectal cancer, with tumor invasion to the sacrum and levator muscle of the anus and multiple lymph node metastasis. After construction of an artificial anus, chemotherapy was started. However, tumor invasion and the cancer pain progressed. Finally, she was hospitalized for pain control; an anesthesiologist planned to insert an epidural catheter. The epidural catheter was placed at the L5-S1 interspace, and continuous administration of 0.2% ropivacaine was started. Cancer pain in the buttocks improved quickly. Therefore, an epidural catheter with a subcutaneous port was placed to prevent catheter-related infection after a long period. The postoperative course was uneventful, and she was discharged from the hospital on the 10th day postoperatively. She could receive home medical care and pain control treatment in an outpatient clinic. Finally, she died due to progression of the rectal cancer, 3 months after placement of the epidural catheter with the subcutaneous port. Some patients with advanced rectal cancer develop cancer pain even though they are sufficiently treated with opioids or palliative radiation therapy. Here, we describe the case of a patient with locally advanced rectal cancer, treated with an epidural catheter with a subcutaneous port for cancer pain that was difficult to manage with opioids alone.

Albumin-derived Neutrophil-to-Lymphocyte Ratio Score as a Marker of Nivolumab Treatment Sensitivity in Gastric Cancer: A Multicenter Study.

BACKGROUND/AIM: Establishment of powerful and easy-to-evaluate biomarkers that can predict immune checkpoint inhibitor sensitivity in patients with gastric cancer (GC) would be highly useful. The albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score reportedly is an excellent measure of both immunity and nutritional status. However, the association between nivolumab treatment sensitivity and Alb-dNLR in GC has also not been adequately investigated. This multicenter retrospective study was designed to evaluate the association of Alb-dNLR with therapeutic sensitivity of nivolumab in GC patients. PATIENTS AND METHODS: This was a retrospective multicenter study with patients from five sites. The data from 58 patients who received nivolumab for postoperative recurrent or unresectable advanced GC between October 2017 and December 2018 were analyzed. Blood tests had been performed before nivolumab administration. We analyzed the correlation between the Alb-dNLR score and clinicopathological factors, including best overall response. RESULTS: Of the 58 patients, 21 (36.2%) comprised the disease control (DC) group and 37 (63.8%) comprised the progressive disease (PD) group. The nivolumab treatment responses were subjected to receiver operating characteristic analysis. The cutoff value was set to 2.90 g/dl for Alb and to 3.55 for dNLR. All eight patients in the high Alb-dNLR group had PD (p=0.0049). The low Alb-dNLR group had significantly better overall survival (p=0.0023) and progression-free survival rates (p<0.0001). CONCLUSION: The Alb-dNLR score was a very simple and sensitive predictor of nivolumab therapeutic sensitivity and has very good biomarker properties.

Gangrenous ischemic colitis localized to the cecum: a case report.

BACKGROUND: Ischemic colitis affects the left colon in elderly individuals and localization on the right side, especially in the cecum, is rare. We report a case of gangrenous ischemic colitis localized in the cecum of a patient undergoing hemodialysis. CASE PRESENTATION: A 73-year-old man had been undergoing hemodialysis for chronic renal failure caused by diabetic nephropathy. He experienced frequent vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography revealed thickening of the cecal wall, poor enhancement, dilation of the cecum, and intrahepatic portal emphysema. No obvious abnormal findings were observed in the appendix. The patient was diagnosed with cecal necrosis and ileocecal resection was performed. Histopathological examination revealed gangrenous ischemic colitis of the cecum. He was discharged 12 days after surgery without postoperative complications. CONCLUSION: It is important to consider the possibility of ischemic colitis of the right colon in the event of renal failure requiring dialysis, to ensure that opportunities for surgical intervention are not missed.

Examining the Efficacy of Nivolumab for Gastric Cancer Focusing on Using an Inflammation-based Prognostic Score: A Multicenter Retrospective Study.

BACKGROUND/AIM: To discover the positive therapeutic effects of nivolumab in patients with advanced gastric cancer (AGC), it is necessary to establish a useful biomarker to predict therapeutic efficacy. This multicenter retrospective study sought to evaluate the predictive impact of inflammation-based prognostic score (IBPS) on the therapeutic efficacy of nivolumab in patients with AGC. PATIENTS AND METHODS: In this retrospective study, we evaluated 58 AGC patients treated with nivolumab from October 2017 to November 2018 at five institutes. Patients were categorized follows: progressive disease (PD) or disease control (DC). Blood chemistry tests were performed immediately before and after two courses of nivolumab; the correlation between best overall response and IBPS was investigated. Transition of each blood serum marker was also assessed. RESULTS: Of 58 patients, 37 (63.8%) were in the PD group and 21 (36.2%) in the DC group. No positive correlation was noted between IBPS and therapeutic efficacy of nivolumab both immediately before and after two courses of nivolumab. However, the neutrophil-lymphocyte ratio (NLR) (p=0.045) and prognostic index (PI) (p=0.0042) before nivolumab and NLR (p=0.025), PI (p=0.0030) and Glasgow prognostic score (GPS) (p=0.043) after nivolumab were significantly correlated with treatment sensitivity. Furthermore, a decrease in PNI was an independent prognostic factor to predict nivolumab resistance on univariate analyses (p=0.0051). CONCLUSION: Although no association between IBPS and therapeutic sensitivity was found, it is important to focus on the transition of PNI to predict therapeutic efficacy of nivolumab.

Laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy for superior mesenteric artery syndrome with dysphagia: a case report.

BACKGROUND: Superior mesenteric artery (SMA) syndrome denotes a mechanical duodenal obstruction between the SMA and aorta. Total parenteral or enteral nutrition is the treatment of choice. However, surgical intervention is indicated if the patient's condition does not improve with conservative treatment. Here, we describe a case of SMA syndrome with dysphagia treated by laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy. CASE PRESENTATION: A 64-year-old man was admitted to another hospital because of appetite loss and vomiting. There, he was diagnosed as having superior mesenteric artery (SMA) syndrome after appropriate investigation. He had had a cerebral infarction at age 57 years, since which he had lived in social housing because of complications of that infarction. A nasogastric tube was inserted into the third portion of the duodenum beyond the constricted section. He was discharged 2 months after admission his condition having improved. He was subsequently referred to our hospital for gastrostomy because the nasogastric tube had been in place for a long time and his condition had not improved. Additionally, gastrostomy was needed as a route for enteral nutrition because he had dysphagia, which had persisted despite attempts at rehabilitation, restricting his food intake to small amounts. Computed tomography (CT) revealed compression of the third portion of the duodenum between the SMA and aorta. After obtaining informed consent, we planned an operative procedure. We performed laparoscopic gastrojejunostomy under general anesthesia, followed by laparoscopic-assisted percutaneous endoscopic gastrostomy. The operation time was 156 min and there was little blood loss. Contrast radiography on postoperative day 3 revealed no evidence of leakage or stenosis. Enteral nutrition via the gastrostomy was started. He was discharged from our hospital on the 27th postoperative day. The gastrostomy was well tolerated and there has been no evidence of recurrence of SMA syndrome during follow-up. CONCLUSION: Gastrostomy is often performed to provide a route for administering enteral nutrition in patients with dysphagia. Development of SMA syndrome in patients with dysphagia necessitates operative management of the obstruction. Here, we describe a case of SMA syndrome with dysphagia treated by laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy.

Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study.

BACKGROUND: Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS: We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS: Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS: GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.

Coexistence of superficial carcinogenesis of resident epithelium besides neuroendocrine neoplasm of the digestive tract.

BACKGROUND & AIMS: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non-neuroendocrine components. Although the coexistence pattern of neuroendocrine and non-neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract. METHODS: From 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals. RESULTS: Among the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ. CONCLUSIONS: These findings suggested a potential "paratransformation" or "bystander effect" in resident epithelium by NENs. Thus, "bystander carcinogenesis" could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract.

Patient with gastric cancer who underwent distal gastrectomy after treatment of COVID-19 infection diagnosed by preoperative PCR screening.

BACKGROUND: Because of the coronavirus disease 2019 (COVID-19) pandemic, preoperative screenings for COVID-19 infection are often performed in many institutions. Some patients are diagnosed with COVID-19 infection by antigen tests or polymerase chain reaction (PCR) testing for COVID-19, even if they have no symptoms, such as fever or respiratory symptoms. We herein describe a patient with gastric cancer who underwent distal gastrectomy 6 weeks after recovering from COVID-19 infection diagnosed by preoperative PCR. CASE PRESENTATION: An 86-year-old man was transferred to our hospital because of hematemesis and melena. A hemorrhagic gastric ulcer was found in the lesser curvature of the antrum by emergency endoscopy. Endoscopic hemostasis was performed, and he was discharged after recovery. A tumor-like lesion in the lesser curvature of the antrum was found on repeat endoscopy and was diagnosed as well-differentiated adenocarcinoma by biopsy. There was no evidence of lymph node metastasis or distant metastasis; therefore, we planned radical surgery. However, he was diagnosed with COVID-19 infection by preoperative PCR screening. Although he had no symptoms, such as fever or respiratory symptoms, he was hospitalized because of his advanced age. He was discharged 10 days after admission, and repeat COVID-19 PCR was negative. We planned radical surgery for the stomach tumor 6 weeks after recovery from the COVID-19 infection. A PCR-negative COVID-19 status was confirmed again before hospitalization. Open distal gastrectomy with Billroth I reconstruction was performed. We avoided ultrasonic scalpels and used a Crystal Vision 450D surgical smoke evacuator (I.C. Medical, Inc., Phoenix, AZ, USA) to reduce intraoperative surgical smoke. The postoperative course was uneventful. CONCLUSION: Because of the COVID-19 pandemic, some patients are diagnosed with COVID-19 infection by preoperative antigen tests or PCR, even if they have no symptoms. If possible, elective surgery should be performed 4 to 6 weeks after recovery from COVID-19 infection to maximize safety. Moreover, surgeons must consider intraoperative surgical smoke.

Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study.

BACKGROUND: Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. METHODS: Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. RESULTS: The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. CONCLUSION: The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

Colon angiolipoma with intussusception resected by laparoscopy-assisted surgery: a case report.

Angiolipomas are benign mesenchymal tumors that often occur under the skin of the upper extremity or thoracic and abdominal walls. Angiolipomas of the digestive tract are rare. Here, we describe a case of transverse colon angiolipoma with intussusception resected by laparoscopy-assisted surgery. A 50-year-old woman visited a family hospital with complaints of left lower abdominal pain and bloody stool. Colonoscopy revealed a submucosal tumor in her left colon. She was referred to our hospital for further examination. Computed tomography revealed a low-density tumor with intussusception in the left transverse colon. Elective surgery was planned for this patient because there were no alarming symptoms such as ileus or obstruction. Laparoscopy-assisted surgery and partial resection of the left transverse colon were performed. The histopathological diagnosis was angiolipoma of the colon. Angiolipomas are benign mesenchymal tumors that rarely occur in the digestive tract. Thus, accurate preoperative diagnosis is difficult.

Large retroperitoneal leiomyoma developed from the pelvic floor to the buttocks.

Retroperitoneal leiomyoma is a very rare disease, with little reported information on its origin. Herein, we report a case of a large retroperitoneal leiomyoma that developed from the pelvic floor. A 44-year-old woman had a large mass protruding outside the body from the right hip. Imaging revealed a large tumor developing from the pelvic floor to the buttocks. It was difficult to identify the place of origin. Upon preoperative biopsy, the patient was diagnosed with retroperitoneal leiomyoma. Tumor removal with abdominoperineal and partial vaginal resection was performed. Based on the histological findings of the surgical specimens, she was diagnosed with a retroperitoneal leiomyoma (gynecologic type) via immunohistochemistry, the tumor cells were positive for αSMA, desmin, estrogen receptor(ER), and progesterone receptor(PgR), but negative for myoglobin, S-100, CD34, and MIB-1.This is a case of a large retroperitoneal leiomyoma that was successfully removed via abdominoperineal and partial vaginal resection.

Thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones in conscious dogs.

This study was conducted to clarify the relationship between thyroid function and gastrointestinal motility. We established an experimental configuration in which the feedback of thyroid function was completely removed using conscious dogs. With hypothyroidism, time of phase I of interdigestive migrating contractions (IMC) was longer, time of phase II and phase III was significantly shortened, and both the continuous time of strong tetanic contraction at antrum and 10-h frequency of phase III counted from the first IMC after meal significantly decreased. Whereas, hyperthyroidism caused the opposite events to those with hypothyroidism. Furthermore, We found giant migrating contractions (GMC) occurred from the upper gastrointestinal tract when we administrated high dose of thyroid hormone. One GMC occurred from anal sides propagated to cardiac, and this propagation was similar to the emesis-like interdigestive motor activity, the other GMC occurred from oral sides propagated to anal sides and this was similar to the diarrhea-like interdigestive motor activity. We examined the relationship between thyroid function and gastrointestinal hormones including of ghrelin, GLP-1, and cholecystokinin (CCK). However, we could not find significant differences under different thyroid hormone status. This is the first report that thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones.

Impact of neutrophil-lymphocyte ratio, Glasgow Prognostic Score, and postoperative decrease in psoas muscle index on recurrence after curative gastrectomy.

Aim : We investigated whether preoperative or postoperative inflammatory markers and psoas muscle index (PMI), and their change after surgery, could predict postoperative recurrence in gastric cancer (GC). Methods : Thirty-five patients who underwent curative gastrectomy for pStage II and III GC were retrospectively reviewed. The relationship between neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), and PMI, as well as postoperative recurrence, was analyzed presurgery and at 6 months after surgery. Results : In the preoperative data, there was a significant association between postoperative recurrence and high NLR, low total protein, low albumin, low PNI, and high GPS. In the data from 6 months after surgery, there was a significant association between postoperative recurrence and high NLR, high C-reactive protein, and high GPS. The reduction in PMI at 6 months after surgery relative to preoperative data was significantly greater in the cases with recurrence than in those without recurrence. No patients whose PMI increased compared with presurgery had recurrence. Conclusions : The postoperative reduction in PMI at 6 months after surgery relative to presurgery could be a predictive marker of recurrence after curative gastrectomy for patients with pStage II and III GC. J. Med. Invest. 68 : 119-124, February, 2021.

Risk Factors for Postoperative Liver Enzyme Elevation After Laparoscopic Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Laparoscopic gastrectomy (LG) is more frequently associated with postoperative liver enzyme elevation (PLEE) than open gastrectomy in phase III clinical trials for Japanese gastric cancer patients. The aim of this study was to determine the risk factors for PLEE after LG for gastric cancer. PATIENTS AND METHODS: This study enrolled 153 consecutive patients with gastric cancer who underwent LG. The patient characteristics, the liver retraction method [silicone disc (SD) or Nathanson liver retractor (NLR)], and perioperative outcomes were compared between patients with and without PLEE. RESULTS: PLEE was observed in 26 patients (17%). The patients with PLEE exhibited longer operative times (p=0.005) and more frequent use of the NLR for liver retraction (p=0.022). In the multivariate analysis, liver retraction using the NLR (p=0.003) and aberrant left hepatic artery (ALHA) ligation (p=0.042) were independent risk factors of PLEE. CONCLUSION: Liver retraction with the SD during LG was shown to be the safer method that is less likely to cause postoperative liver dysfunction. ALHA preservation may contribute to avoiding postoperative liver dysfunction.

Clinical outcomes of gastric tube reconstruction following laparoscopic proximal gastrectomy for early gastric cancer in the upper third of the stomach: experience with 100 consecutive cases.

BACKGROUND: Gastric tube reconstruction is a form of esophagogastrostomy performed after laparoscopic proximal gastrectomy (LPG). It is a simple and safe technique, but it may cause reflux esophagitis (RE) and impair postsurgical QOL. For several years, we have developed the gastric tube reconstruction and performed it on more than 100 patients. This study aimed to determine whether gastric tube reconstruction can be a feasible choice after LPG in regard to surgical safety and postoperative nutritional status. METHODS: The subjects consisted of 171 patients who underwent LPG (n = 102) or laparoscopic total gastrectomy (LTG) (n = 69). We compared the two groups in terms of surgical outcomes, incidence rate of RE, and nutritional status including postoperative weight loss and hemoglobin levels. RESULTS: There were no significant differences with regard to the surgical duration and blood loss between the two groups. The incidence of RE was not significantly higher with LPG than with LTG (16.7% vs. 10.1%, respectively; P = 0.07). Later than 2 years and 6 months after surgery, the body weight percentage of preoperative body weight in the LPG group was significantly higher than that in the LTG group. Hemoglobin and ferritin levels in the LPG group were significantly higher than those in the LTG group, later than one after surgery. The overall survival rates were similar between the two groups (5-year survival rates: 97.1% vs. 94.2% in the LPG and LTG groups, respectively; P = 0.69). CONCLUSIONS: Gastric tube reconstruction after LPG is simple and had better outcomes than LTG in terms of postoperative nutritional status.

Impact of combined assessment of systemic inflammation and presarcopenia on survival for surgically resected esophageal cancer.

BACKGROUND: Systemic inflammation and low skeletal muscle volume (presarcopenia) have received increasing attention in many malignancies. However, their association and the combined effect on postoperative survival in esophageal cancer (EC) patients have been poorly studied. METHODS: Eighty-nine patients with EC who underwent surgery between 2006 and 2014 were included in this study. Neutrophil-to-lymphocyte ratio (NLR) ≥3.0 was categorized as having systemic inflammation. Presarcopenia was defined as a Skeletal muscle index (SMI) less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women. RESULTS: Multivariate analysis revealed that presarcopenia was an independent prognostic preoperative factor for overall survival (OS) (p = 0.004). Multivariate analysis for OS stratified by systemic inflammation revealed that presarcopenia with systemic inflammation (Hazard ratio(HR),20.70; 95% confidence interval (CI),1.34-318.90) was associated with nearly a seven-fold higher risk of death than those without systemic inflammation (HR, 2.94; 95%CI, 1.04-8.34). CONCLUSIONS: Systemic inflammation enhanced the effect of presarcopenia on the prognosis of EC patients. The combined assessment of those factors may have potential prognostic value for EC.

Migrating contractions of the afferent and Roux limbs show peristaltic movement independently of each other in conscious dogs after Roux-en-Y reconstruction after distal gastrectomy.

PURPOSE: The Roux-en-Y (RY) procedure is used frequently for surgical reconstruction after gastrectomy. However, a minority of patients suffer a serious motility disorder of the Roux and afferent limb postoperatively. We conducted this study to clarify the association between the motility and peristaltic direction of two limbs in conscious dogs. METHODS: We performed distal gastrectomy on five dogs and implanted seven force transducers on the serosal surfaces of the remnant gastric body and afferent and Roux limbs. We then analyzed the electric signals from these force transducers. RESULTS: Migrating contractions were observed in the two limbs, but not in the gastric remnant body. Migrating contractions in the forward direction propagated independently from the most proximal side in each limb. There was no propagation of contraction across the jejunojejunostomy between the two limbs. CONCLUSIONS: Each proximal part of the Roux and afferent limbs has an independent motility pacemaker in conscious dogs after gastrectomy with RY reconstruction.

Chest Pain after Endoscopic Submucosal Dissection for Esophageal Cancer: The Simple and Clinically Useful Surrogate Marker for Transmural Thermal Injury by Electrocoagulation.

BACKGROUND: Endoscopic submucosal dissection (ESD) of early esophageal cancer (EC) is becoming more widespread. Post-ESD coagulation syndrome (CS) has been proposed as temporary inflammatory signs that occur during the post-ESD period caused by transmural thermal injury by electrocoagulation. This retrospective study aimed to evaluate the association between chest pain and abnormal levels of inflammatory markers during the post-esophageal ESD period. We also investigate the clinical importance of chest pain to define the post-esophageal ESD CS. METHODS: We examined 42 patients with thoracic EC who underwent ESD. RESULTS: The incidence of chest pain after esophageal ESD is 35.7% and associated with elevation of WBC count on postoperative day 1 (WBC day 1) (p = 0.022). Multivariate logistic regression analysis using the procedure-related factors revealed that WBC day 1 was an independent predictive factor for chest pain (p = 0.034). The elevation of WBC count is associated with the resected esophageal circumference (p for trend = 0.018), specimen size (p = 0.031), and procedural time (p = 0.004). The incidence of post-esophageal ESD CS was estimated ranging from 11.9 to 54.8% using previously reported criteria. CONCLUSIONS: The incidence of chest pain after ESD was only associated with postoperative elevation of WBC day 1. In considering the elevation of WBC count associated with procedure-related factors, chest pain possibly reflected transmural thermal injury by electrocoagulation during ESD. Post-esophageal ESD chest pain is a simple and clinically useful surrogate marker for transmural thermal injury and is a vital sign of post-esophageal ESD CS.

Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer.

INTRODUCTION: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. OBJECTIVE: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. METHODS: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8+ lymphocytes expressing PD-1 and CD163+ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. RESULTS: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. CONCLUSIONS: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.