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Abstract Background Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD‐L1 expression and tumor‐infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD‐L1 expression and TILs in ESCC. Methods Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. Results PD‐L1 was expressed in tumor cells (PD‐L1 TC). PD‐L1 TIIC and PD‐L1 TC affected the biological behavior of TC. The positive expression rate of PD‐L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan–Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD‐L1 TC‐positive expression, which promote ESCC progression and metastasis. Conclusion Tumor depth, CD8, and PD‐L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune‐related factors is beneficial for stratifying patient survival risk.

Abstract Background Small bowel cancer is very rare, accounting for less than 5% of all gastrointestinal cancers, and small bowel adenocarcinoma accounts for approximately 40% of all small bowel cancers. Small bowel adenocarcinoma is often found in advanced stages, with only 40–65% of cases being curatively resectable. The prognosis is poor, with a 5-year survival rate of 14–33% for all patients and 40–60% for those who are curatively resectable. In Japan, practice guidelines for duodenal cancer were instituted in 2021. However, evidence-based standard treatments have not been established for jejunal and ileal cancers. In particular, chemotherapeutic options are limited, and there are only a few reports on multidisciplinary treatments, including adjuvant chemotherapy. Case presentation We report five cases of jejunal or ileal lesions that were treated with adjuvant chemotherapy after radical resection. Three patients were male and two were female, with a median age of 67 years. Tumor localization was observed in the jejunum in all cases. Clinical staging was as follows: stage IIIA in two cases and stage IIIB in three cases. Laparotomy was then performed in all cases, employing partial resection with lymph node dissection. Pathological staging in all cases was as follows: stage IIB in two cases, stage IIIA in one case, and stage IIIB in two cases. In all cases, the regimen for adjuvant chemotherapy was selected based on the colorectal cancer guidelines. No serious complications arose from adjuvant therapy; however, adverse events occurred in patients receiving multi-agent chemotherapy. No recurrence was observed in any of the cases, and all the patients survived, with a median survival time of 32 months. As a representative case, we present a case of adjuvant chemotherapy for jejunal adenocarcinoma staged as pT3N2M0, pStage IIIB, with no recurrence at 32 months postoperatively. Conclusions In general, favorable outcomes were achieved with adjuvant therapy applied in accordance with the criteria for colorectal cancer. These favorable outcomes suggest that it is necessary to identify the risk factors and indications for adjuvant therapy, specifically for small bowel adenocarcinoma.

Abstract Aim According to the current guidelines in Japan, the upper age limit for bariatric and metabolic surgery is 65 y. This study aimed to examine the appropriateness of this upper age limit. Methods Using the database maintained by the Japanese Society for Treatment of Obesity, we conducted an analysis of patients in two age groups: those aged

Abstract Aim The current study compared the postoperative quality of life (QOL) between the esophagogastrostomy method (PGEG) and double tract method (PGDT) after proximal gastrectomy using the Postgastretomy Syndrome Assessment Scale (PGSAS)‐45. Methods Among the 2364 patients who received the PGSAS‐45 questionnaire, 300 PGEG and 172 PGDT cases responded. The main outcomes measures (MOMs) consisted of seven subscales (SS) covering symptoms, meals (amount and quality), ability to work, dissatisfaction with daily life, physical and mental component summary of the 8‐Item Short Form Health Survey (SF‐8), and change in body weight, and were compared between PGEG and PGDT. Results Overall, PGDT promoted significantly better constipation SS scores (p

Abstract Colorectal cancer (CRC) is the third most prevalent cancer in the world, yet the sensitivity and specificity of biomarkers for CRC diagnosis are insufficient. In the present study, we performed a protein microarray screening method to identify antibody markers for CRC. Inhibitor of growth family 1 (ING1) was identified as a candidate tumor antigen for CRC using protein microarrays (ProtoArray). Subsequent amplified luminescence proximity homogeneous assay-linked immunosorbent assay using recombinant ING1 protein showed that the serum levels of anti-ING1 antibodies were increased not only in patients with CRC but also in those with esophageal cancer (EC), gastric cancer (GC), breast cancer (BrC), and pancreatic cancer (PC) compared with those of healthy donors (HDs). Antibodies against the ING1 amino acids between 239 and 253 were present at significantly higher levels in patients with CRC than in those with EC, GC, BrC, or PC. Anti-ING1 antibody levels were significantly higher in the patients with CRC at any stages than in the HDs. Immunohistochemical staining revealed higher expression of ING1 protein in CRC cells than in the adjacent normal tissues. In luciferase reporter assays using a CRC cell line, ING1 augmented p53-mediated NOXA promoter activity but attenuated p53-stimulated Bax, p21, and PUMA promoter activities. Consequently, serum anti-ING1 antibodies can be used for sensitive and specific diagnoses of CRC.

Abstract There is no preoperative imaging accurately diagnose malignancy of gastrointestinal stromal tumor (GIST). To evaluate the usefulness of preoperative [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the malignant diagnosis and prognostic analysis of GIST. Eighty-nine consecutive patients with GIST who underwent curative surgery were reviewed retrospectively. PET scan was performed within 2–3 weeks before surgery and maximum standardized uptake values (SUVmax) were assessed for GIST. The relationship between prognostic factors and prognosis of GIST and SUVmax were evaluated. Tumor size, mitotic count, and Ki-67 index showed significant positive correlations with the SUVmax. When the cutoff value was set as SUVmax 5.68, the accuracy was 86.5% for the high-risk group, 76.4% for the recurrence group, and 73.0% for the death group. The group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year relapse-free survival than the group with SUVmax

Abstract The combined use of a vital dye and radioactive colloid reportedly performs better in detecting sentinel lymph nodes (SLNs) for cancers than the use of either of them alone. However, especially for gastric cancer, two endoscopic procedures are required to administer these two tracers, which burdens the patients and practitioners. Here we propose the use of stannous colloid (SnC) mixed with indocyanine green (ICG) as a new mixed tracer (SnC–ICG); its characteristics were investigated in vivo and in vitro to estimate its usefulness for SLN navigation. The tracers were administered to rats and the accumulation of radioactivity and/or near-infrared fluorescence were evaluated in the regional lymph nodes (LNs) using single positron emission computed tomography and near-infrared fluorescence imaging, respectively. SnC–ICG showed significantly better clearance from the injection site and better migration to primary LNs than the single administration of SnC or ICG aqueous solution. SnC–ICG demonstrated a wide particle size variability, stabilized to 1200-nm upon the addition of albumin in vitro; These properties could contribute to its behavior in vivo. The use of SnC–ICG could contribute better performance to detect SLNs for gastric cancer with less burden on both patients and medical practitioners.

The RNA-binding protein LIN28B is overexpressed in over 30% of patients with colorectal cancer (CRC) and is associated with poor prognosis. In the present study, we unraveled a potentially novel mechanism by which LIN28B regulates colonic epithelial cell-cell junctions and CRC metastasis. Using human CRC cells (DLD-1, Caco-2, and LoVo) with either knockdown or overexpression of LIN28B, we identified claudin 1 (CLDN1) tight junction protein as a direct downstream target and effector of LIN28B. RNA immunoprecipitation revealed that LIN28B directly binds to and posttranscriptionally regulates CLDN1 mRNA. Furthermore, using in vitro assays and a potentially novel murine model of metastatic CRC, we show that LIN28B-mediated CLDN1 expression enhances collective invasion, cell migration, and metastatic liver tumor formation. Bulk RNA sequencing of the metastatic liver tumors identified NOTCH3 as a downstream effector of the LIN28B/CLDN1 axis. Additionally, genetic and pharmacologic manipulation of NOTCH3 signaling revealed that NOTCH3 was necessary for invasion and metastatic liver tumor formation. In summary, our results suggest that LIN28B promotes invasion and liver metastasis of CRC by posttranscriptionally regulating CLDN1 and activating NOTCH3 signaling. This discovery offers a promising new therapeutic option for metastatic CRC to the liver, an area where therapeutic advancements have been relatively scarce.

The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62–RBP6 interaction.

Abstract This study aimed to evaluate the uptake of the clinical effectiveness of [S-methyl-11C]-L-methionine positron emission tomography/computed tomography (MET PET/CT) in patients with esophageal cancer and to investigate MET PET/CT imaging parameters to assess early response for esophageal cancer with neoadjuvant carbon ion radiotherapy (CIRT). MET PET/CT scans were performed in nineteen patients before and 3 weeks after completion of CIRT. After Surgery, the effect of neoadjuvant CIRT was investigated by examining the relationship between each parameter of MET uptake and the histological assessment (grade and tumor residual ratio). Four parameters of MET uptake were the maximum and minimum standardized uptake values of pre and post CIRT (pre-SUVmax, pre-SUVmean, post-SUVmax, and post-SUVmean). MET PET/CT imaging of esophageal cancer was clearly demonstrated. The post-SUVmax was the most suitable parameter. When the cutoff value was set as post-SUVmax = 6.21, the sensitivity, the specificity, and the accuracy of Grades 3 were 100.0%, 63.6%, and 78.9%, respectively. And there was a positive relationship between the tumor residual ratio and post-SUVmax (R 2 = 0.38, p

Abstract Smad ubiquitination regulatory factor 2 (Smurf2) plays various roles in cancer progression. However, the correlation between Smurf2 and clinical outcomes has not been determined in patients diagnosed with colorectal cancer and colorectal liver metastases. We analyzed 66 patients with colorectal cancer who developed liver metastases. Smurf2 expression was assessed using immunohistochemical analysis of primary and metastatic liver tumors. High Smurf2 expression in both primary and metastatic tumors was significantly associated with longer overall survival time and time to surgical failure. Multivariate analyses revealed that low Smurf2 expression in primary tumors was an independent predictor of poor prognosis. In vitro experiments using colon cancer cell lines demonstrated that short interfering RNA knockdown of Smurf2 increased cell migration and tumor sphere formation. Western blot analyses revealed that Smurf2 knockdown increased the protein expression of epithelial cell adhesion molecule (EpCAM). Thus, in summary, high Smurf2 expression in cancer cells was found to be an independent predictor of better prognosis in patients with primary colorectal cancer and consequent liver metastases. The tumor-suppressive role of Smurf2 was found to be associated with cell migration and EpCAM expression; hence, Smurf2 can be considered a positive biomarker of cancer stem cell-like properties.

Abstract Background Voriconazole (VRCZ) is the first-line therapy for chronic pulmonary aspergillosis and is available in both intravenous and oral formulations. The bioavailability of the oral form is estimated to be over 90% in healthy volunteers. Some drugs are reported to interact with enteral nutrition (EN), but there are few reports about the trough levels of VRCZ during EN therapy. Here, we describe changes in the VRCZ trough levels in a patient receiving continuous EN therapy. Case presentation The patient was a 58-year-old man with esophageal cancer and a history of partial pulmonary resection due to aspergilloma. He was taking oral VRCZ tablets and his VRCZ trough level was about 2 μg/mL before esophageal cancer surgery. Following esophagectomy, VRCZ was restarted on postoperative day 16. Crushed VRCZ tablets were administered via a jejunostomy tube because of swallowing difficulty. He was also receiving EN, which was interrupted only during the administration of VRCZ. When we checked his VRCZ level 5 days after restarting VRCZ, the trough level was 0.80 μg/mL. After increasing the VRCZ dose, reducing EN, and changing the administration route from jejunostomy tube to oral, his trough level increased to 1.87 μg/mL. Conclusions A decrease in the VRCZ trough level was observed when VRCZ was administered via a jejunostomy tube while the patient was receiving continuous EN. Careful monitoring of VRCZ levels is needed in such cases.

Abstract One of the complications of esophageal endoscopic submucosal dissection (ESD) is postoperative stricture formation. Stenosis formation is associated with inflammation and fibrosis in the healing process. We hypothesized that the degree of thermal damage caused by the device is related to stricture formation. We aimed to reveal the relationship between thermal damage and setting value of the device. We energized a resected porcine esophagus using the ESD device (Flush Knife 1.5). We performed 10 energization points for 1 s, 3 s, and 5 s at four setting values of the device. We measured the amount of current flowing to the conducted points and the temperature and evaluated the effects of thermal damage pathologically. As results, the mean highest temperatures for 1 s were I (SWIFT Effect3 Wat20): 61.19 °C, II (SWIFT Effect3 Wat30): 77.28 °C, III (SWIFT Effect4 Wat20): 94.50 °C, and IV (SWIFT Effect4 Wat30): 94.29 °C. The mean heat denaturation areas were I: 0.84 mm2, II: 1.00 mm2, III: 1.91 mm2, and IV: 1.54 mm2. The mean highest temperature and mean heat denaturation area were significantly correlated (P

Abstract Background Arteriovenous malformation (AVM) of the gastrointestinal (GI) tract can cause bleeding. The treatment choice for GI tract AVM is surgical resection of the involved bowel segment with complete resection of the nidus. The AVM formed in the duodenum or pancreatic head could also cause gastrointestinal bleeding, and there are several reports of pancreaticoduodenectomy as its treatment. However, if the area of AVM can be accurately identified during surgery, it may be possible to completely resect the AVM while preserving the organ. We report a case of duodenal AVM in a patient successfully treated with a subtotal stomach-preserving duodenal bulb resection using intraoperative indocyanine green (ICG) angiography technique. Case presentation An 18-year-old man was diagnosed with duodenal AVM after several examinations for anemia and was referred to our hospital for further treatment. Preoperative imaging studies showed that the inflow vessels of this duodenal AVM were the inferior pyloric artery and the superior duodenal artery, and the AVM was localized to the duodenal bulb. Thereafter, stomach-preserving duodenal bulb resection preceded by ligation of the inflow vessels was performed. During the surgery, ICG angiography clearly demonstrated the area, where the nidus was distributed, and a duodenal bulb resection with complete resection of the AVM was successfully performed. There was no recurrence at the 6-month follow-up. Conclusions Intraoperative ICG angiography was a useful procedure for precise identification of the AVM of the GI tract.

Abstract Background Esophagectomy followed by gastric conduit reconstruction is a standard surgical procedure for esophageal cancer. However, there is no evidence of the superiority or inferiority of the posterior mediastinal (PM) versus the retrosternal (RS) reconstruction route with regard to short‐term outcomes after esophagectomy. We aimed to elucidate whether the reconstruction route can affect the short‐term outcomes after esophagectomy followed by gastric conduit reconstruction. Methods We reviewed the clinical data of patients who underwent esophagectomy between 2016 and 2018 from the Japanese National Clinical Database. This study included 9786 patients who underwent gastric conduit reconstruction through the PM or RS route with cervical anastomosis. Results Of the 9786 patients analyzed, 3478 and 6308 underwent gastric conduit reconstruction thorough the PM and RS routes, respectively. The incidence of anastomotic leak and surgical site infection (SSI) was significantly lower in the PM group than in the RS group (11.7% vs 13.8%, P = .005 and 8.4% vs 14.9%, P

Introduction: Laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients often result in remission of type 2 diabetes (T2DM), but diabetes relapses in some of those patients. The frequency of T2DM relapse in Asians and the factors involved have not been adequately investigated. Methods: The J-SMART study was conducted on 322 Japanese subjects with body mass index (BMI) ≥ 32 kg/m2 who underwent LSG at 10 accredited centers in Japan between 2011 and 2014. Of these, 82 T2DM subjects with diabetes in complete or partial remission at 1 year after LSG and followed postoperatively for 5 years were included in the subgroup analysis, and classified into two groups: diabetes remission maintained and diabetes relapse. Results: The mean age of all included subjects was 49.2 years, median BMI was 41.5 kg/m2, and median was HbA1c 6.7%. Compared with the diabetes remission maintained group, the diabetes relapse group at 5 years after LSG had significantly higher preoperative HbA1c, number of antidiabetic medications, and high-density lipoprotein cholesterol level; and lower BMI and homeostasis model assessment-beta cell function (HOMA-β). As many as 83.0% of the subjects were able to achieve HbA1c < 7% at 5 years after LSG, but 26.8% of the subjects had diabetes relapse. Preoperative HbA1c significantly contributed to diabetes relapse (odds ratio 1.54, p = 0.049). In addition, the diabetes relapse group tended to have lower percent total weight loss (%TWL) at 1 year after LSG and higher percent weight regain (%WR) from postoperative nadir weight, compared with the diabetes remission maintained group. The hazard ratio for diabetes relapse was 3.14-fold higher in subjects with %TWL ≥ 20% and %WR ≥ 25%, and 5.46-fold higher in those with %TWL < 20% and %WR ≥ 25%, compared with %TWL ≥ 20% and %WR < 25%. Conclusion: While LSG provides a high remission rate for T2DM, relapse is not uncommon. Preoperative HbA1c, poor weight loss and excess weight regain after LSG contribute to diabetes relapse, suggesting the importance of treatment strategies focusing on these factors.

Abstract Background Evaluating the effect on primary lesions is important in determining treatment strategies for esophageal cancer. The Response Evaluation Criteria in Solid Tumors system, which employs the longest diameter for measuring tumors, is commonly used for evaluating treatment effects. However, the usefulness of these criteria in assessing primary esophageal tumors remains controversial. Thus, we evaluated this issue by measuring not only the longest diameter but also the shorter axis of the tumor. Methods We retrospectively reviewed data from 313 patients with esophageal cancer treated with neoadjuvant chemotherapy followed by esophagectomy at three major high-volume centers in Japan. All patients underwent contrast-enhanced computed tomography before and after chemotherapy. The longest and shortest tumor diameters were measured in each case. Treatment effects were adapted to the Response Evaluation Criteria in Solid Tumors system. Correlations between pathological and survival data were also analyzed. Results Inter-observer discrepancies were examined for changes in the longest diameter and shorter axis of the tumor (the intraclass correlation coefficients were 0.550 and 0.624, respectively). The shorter axis was correlated with the pathological response in the multivariate analysis (p

Abstract Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

Abstract Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

Introduction: The psychosocial background of subjects with severe obesity developed from childhood onset obesity (CO) and their outcomes after bariatric surgery have not been fully investigated. Methods: 305 subjects were enrolled in the J-SMART study, which examined the effects of laparoscopic sleeve gastrectomy (LSG) in Japan, and categorized into two groups: CO defined as onset up to 13 years of age (CO group) and post-puberty onset obesity defined as onset after 13 years of age (PPO group). The subjects were followed up for at least 2 years and up to 5 years after LSG. Changes in physical parameters and remission of obesity-related comorbidities were assessed at 2 years after LSG. Weight regain (WR) was also assessed by evaluating the nadir weight after LSG and maximum weight thereafter during follow-up period. Results: The mean postoperative follow-up period was 3.0 ± 1.1 years. 40.0% of the subjects had CO and these subjects had higher BMI and HOMA-β, and lower age, HbA1c, HDL cholesterol, and visceral/subcutaneous fat area ratio compared to those with PPO. The CO group was also characterized by having higher rates of mental retardation, developmental disorders and obesity in either parent, and lower rate of marriage compared to the PPO group. Two years after LSG, there were no differences in total weight loss and remission rates of diabetes, dyslipidemia and sleep apnea syndrome between the two groups, although remission rate of hypertension was higher in the CO group. The CO group also had a higher rate of WR after LSG than the PPO group, with CO, BMI, mental disorder and binge eating contributing to WR. Conclusion: This study suggests that CO might be associated with genetic and psychosocial factors. CO and PPO probably differ in pathogenesis and may require different treatment strategies.

Abstract Background Since the ToGA trial, trastuzumab-based chemotherapy is the standard treatment for HER2 positive stage IV gastric cancer. However, it is not yet clear whether surgical resection after trastuzumab-based chemotherapy (conversion surgery) can improve survival of HER2 positive stage IV gastric cancer. The purpose of this study is to evaluate the prognostic benefit of conversion surgery in HER2 positive stage IV gastric cancer patients. Case presentation We retrospectively investigated the medical records of the patients with HER2 positive (IHC3(+) or IHC2(+)/FISH(+)) stage IV gastric cancer treated with trastuzumab-based chemotherapy as the first line treatment. Overall survival (OS) was compared between patients with conversion surgery and without. Eleven HER2 positive stage IV gastric cancer patients treated with trastuzumab-based chemotherapy as the first line treatment were evaluated. Response rate was 63.6%, and 6 of 11 patients could receive conversion surgery. R0 resection was achieved in four patients. In Kaplan–Meier analysis, patients who received conversion surgery showed significantly better OS than those without surgery (3-year survival rate, 66.7% vs. 20%, P = 0.03). The median OS of patients who achieved R0 resection is 51.8 months. Conclusions Conversion surgery might have a survival benefit for HER2 positive stage IV gastric cancer patients. If curative surgery is technically possible, conversion surgery could be a treatment option for HER2 positive stage IV gastric cancer.

Abstract Background Esophagostomy is important in the treatment of esophageal cancer. However, esophagectomy has a higher risk of postoperative complications. Treatment for complications is often difficult, and in some cases, oral intake is no longer possible. Recently, magnetic compression anastomosis (MCA) was developed; it is a relatively safe method of anastomosis that does not require surgery in patients with stricture, obstruction, or dehiscence of the anastomosis after surgery. Case presentation The patient was a 76-year-old Japanese man. He underwent esophagectomy with a three-field dissection for esophageal cancer. A cervical esophagostomy and chest drainage were performed for necrosis of the gastric tube. Following infection control, colon interposition was performed. However, after the operation, the colon necrotized and formed an abscess. Drainage controlled the infection, but the colon was completely obstructed. The patient was referred to our hospital to restore oral ingestion. Contrast studies showed that the length of the occlusion was 10 mm. The reconstruction was examined; reanastomosis by surgery was judged to be a high risk, so the strategy of anastomosis by MCA was adopted. In the operation, the anterior chest was opened to expose the colon, and a magnet was inserted directly into the blind end of the colon. The magnet was guided to the blind end of the esophagus using an oral endoscope. Two weeks after MCA, a contrast study confirmed the passage of the contrast agent from the esophagus to the colon. The patient eventually took 18 bougies after the MCA. However, since then, he has not needed a bougie. As of 1 year and 8 months after the MCA, the patient is living at home with oral intake restored. Conclusions MCA is an effective and safe treatment for complete stenosis after esophageal cancer surgery.

Abstract In Japan, the treatment of esophageal cancer has undergone significant development since the Japanese Society for Esophageal Diseases was established in 1965 by Doctors Komei Nakayama, Shigetsugu Katsura, and Ichiro Akakura. When the Society was established, surgery was the first‐line treatment for esophageal cancer. Since then, the Society has been led by three successive chairpersons—Doctors Katsura, Nakayama, and Satoh. Over this time, surgery‐related mortalities declined to 5%‐6% because of the rapid improvements in surgical technique. Beginning in 1980, the bilateral cervical lymph node dissection technique gained attention, and favorable long‐term outcomes were gradually reported. A nationwide questionnaire survey, conducted by the Society in 1990, showed that more favorable long‐term outcomes were achieved by following the three‐field lymph node dissection technique than by following the two‐field lymph node dissection technique. Since then, the three‐field lymph node dissection technique has been recognized and widely used as the standard surgical procedure for treating esophageal cancer. After clinical studies examined the utility of various pre‐ and postoperative adjunctive therapies in outcome improvements, preoperative chemotherapy was recognized as the standard treatment in the therapy guidelines. Additionally, less invasive surgical methods have been developed, including endoscopic and robot‐assisted surgeries, which are applied in general practice now. However, unresectable and recurrent esophageal cancers remain difficult to treat, and additional treatments should be developed.

Abstract Aim Esophageal squamous cell carcinoma (ESCC) is a refractory digestive organ cancer that requires better treatment strategies. We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF‐κB) nuclear translocation. In the present study, we focused on caspase recruitment domain family member 9 (CARD9), an essential signal adapter in NF‐κB activation to examine whether it can be used as a prognostic factor in ESCC. Methods We investigated CARD9 expression immunohistochemically in clinical samples obtained from 93 patients with ESCC who underwent curative esophagectomy. CARD9 expression was analyzed for correlation with clinicopathological characteristics and ESCC prognosis. The molecular effects were investigated by knocking down ESCC cells. Comprehensive RNA expression changes in these ESCC cells were detected by next‐generation sequencing (NGS). Results High CARD9 expression is significantly correlated with advanced tumor depth (P

Abstract Aim Laparoscopic sleeve gastrectomy (LSG) is becoming popular in Japan, but insufficient weight loss is often observed in patients after LSG. We investigated the effect of LSG on obesity‐related comorbidities and identified the background characteristics of Japanese patients with insufficient weight loss after LSG. Methods In this multi‐institutional retrospective study at 10 certified bariatric institutions, 322 Japanese patients who underwent LSG with a follow‐up period of more than 2 years were analyzed. Anthropometry, obesity‐related comorbidities and psychosocial background data were collected. Weight loss was expressed as 2‐year percent total weight loss (%TWL). Results Mean age, body weight, body mass index (BMI) and glycated hemoglobin were 46.9 years, 119.2 kg, 43.7 kg/m2 and 7.1%, respectively. Prevalence of mental disorders was 26.3%. Mean BMI declined to 30.3 kg/m2 at 2 years and %TWL was 29.9%. Improvements in the markers and prevalence of obesity‐related comorbidities were observed. Remission rates of diabetes, dyslipidemia and hypertension were 75.6%, 59.7% and 41.8%, respectively. %TWL at the respective cut‐off level of diabetes remission was 20.8%. Lower remission rates of diabetes in patients with %TWL

Granulomatous appendicitis is uncommon. It can be caused by infectious or systemic disorders, such as Crohn’s disease (CD) and sarcoidosis. It is therefore essential to investigate systematic causes of granulomatous appendicitis after surgery by appropriate examinations. It is also rare for acute appendiceal inflammation to develop due to active CD. We herein report a case of CD presenting as granulomatous appendicitis. The patient was a 28-year-old man who arrived at the emergency room with right lower abdominal pain. Computed tomography showed a low-density lesion with a clear boundary and a small high-density spot in its center behind the cecum. Acute appendicitis with abscess formation was suspected and conservative treatment was started. After 3 consecutive days of conservative treatment there was no improvement in his condition. We therefore performed open appendectomy. Histopathological examination showed numerous noncaseous epithelioid granulomas in the wall of the appendix. Specific staining revealed no evidence of acid-fast bacilli or fungi. During follow-up after discharge, colonoscopy demonstrated erosion from the cecum to the transverse colon. A colon biopsy showed severe inflammation with cryptitis, Paneth cells, and a granulomatous lesion. The patient was therefore diagnosed with CD and treatment with mesalazine was started. Careful examination is necessary to diagnose and properly treat patients with granulomatous inflammation of the appendix.

Abstract Background An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. Methods The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. Discussion The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. Trial registration NCT03222895, date of registration: July 19th, 2017.

Objectives: To clarify the safety and efficacy of celecoxib combined with chemoradiotherapy using S-1 for lower rectal cancer. Methods: Twenty-one patients with pathologically proven lower rectal adenocarcinoma (cT3-T4, Tx N+, M0) were included in this study. A total dose of 45 Gy was administered in daily fractions of 1.8 Gy. Celecoxib was given orally twice daily with S-1 on the day of irradiation. The dose of celecoxib was set at 400 mg/day. In Phase I, the S-1 dose was started at 80 mg/m2/day; in Phase II, S-1 was administered in the same dose as Phase I. Patients underwent surgery six to eight weeks after completing chemoradiotherapy, followed by six months of postoperative adjuvant chemotherapy. Results: The S-1 recommended dose was 80 mg/m2/day. The pathological complete remission rate was 15.8%, the rate of protocol completion was 14.3%, and the rate of adverse events exceeding Grade 3 was 19.0%. Surgery was performed in 19 cases, with a sphincter-sparing rate of 31.6%. Postoperative complications exceeding Grade 3 occurred in 52.4% of cases. The three year overall survival and relapse-free survival rates were 89.3% and 67.0%, respectively. Conclusions: We failed to show a synergistic or additive therapeutic effect of preoperative CRT using S-1, combined with celecoxib, for lower advanced rectal cancer beyond CRT using 5 FU or capecitabine alone. The incidence of complications, evidently involving intestinal ischemia, was relatively high. This treatment strategy is not recommended at present.

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are associated with poor prognoses in patients with gastric cancer; however, few studies have focused on the dynamic changes in these ratios during the treatment of patients with gastric cancer. Here, we assessed the clinical utility of changes in these ratios as prognostic indicators in patients with stage II or III gastric cancer who received adjuvant chemotherapy. Methods We retrospectively reviewed 100 patients who received S-1 adjuvant chemotherapy at ≥70% of the relative dose intensity, and their NLRs and PLRs were evaluated at different times: prior to gastrectomy and upon commencement and termination of adjuvant chemotherapy. To assure the clinical utility of the changes in NLR and PLR as prognostic indicators, other clinical factors were assessed as well. Results Disease recurred in 35 patients as follows: lymph node metastasis (17 patients, 17.0%), peritoneal metastasis (12 patients, 12.0%), and hematogenous metastasis (6 patients, 6.0%); 24 patients died. An increase in the NLR during adjuvant chemotherapy with S-1 was identified as an independent indicator associated with overall survival (hazard ratio [HR] 6.736, 95% confidence interval [CI] 2.420–18.748; P

The numbers of patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), have been increasing over time, worldwide; however, the pathogenesis of IBD is multifactorial and has not been fully understood. Myosin light chain 9 and 12a and 12b (Myl9/12) are known as ligands of the CD69 molecule. They create “Myl9 nets” that are often detected in inflamed site, which play a crucial role in regulating the recruitment and retention of CD69-expressing effector cells in inflamed tissues. We demonstrated the strong expression of Myl9/12 in the inflamed gut of IBD patients and mice with DSS-induced colitis. The administration of anti-Myl9/12 Ab to mice with DSS-induced colitis ameliorated the inflammation and prolonged their survival. The plasma Myl9 levels in the patients with active UC and CD were significantly higher than those in patients with disease remission, and may depict the disease severity of IBD patients, especially those with UC. Thus, our results indicate that Myl9/12 are involved in the pathogenesis of IBD, and are likely to be a new therapeutic target for patients suffering from IBD.

Esophageal squamous cell carcinoma is a malignant tumor with unfavorable prognosis. In this study, we investigated the usefulness of microRNA (miR)-1246 detection in various body fluids as a biomarker for this disease. A total of 72 patients with esophageal squamous cell carcinoma were enrolled, and their blood, urine, and saliva samples were collected prior to treatment. Reverse transcription-polymerase chain reaction of miR-1246 was performed, and pre- and postoperative and intraday fluctuations in its expression were examined. The expression of miR-1246 in the blood and urine was significantly higher in the patients with esophageal squamous cell carcinoma than in 50 healthy control subjects. Receiver operating characteristic curves showed that the area under the curve values were 0.91 (sensitivity 91.7%, specificity 76.0%), 0.82 (sensitivity 90.3%, specificity 62.0%), and 0.80 (sensitivity 83.3%, specificity 66.0%) in the serum, urine, and saliva, respectively. A relatively high diagnostic performance of miR-1246 was observed in all samples, which was better than that of the existing biomarkers squamous cell carcinoma antigen, carcinoembryonic antigen, and cytokeratin 19 fragment. No clear correlation was observed in the levels of miR-1246 expression among the three body fluids. Postoperatively, serum samples displayed significantly decreased miR-1246 levels. Although not significant, changes in the miR-1246 levels were observed at all collection times, with large fluctuations in the saliva. Meanwhile, serum miR-1246 expression was found to be associated with the disease prognosis. The results indicate that the levels of miR-1246 in the urine, saliva, and serum are a useful biomarker for esophageal squamous cell carcinoma and support the use of urine samples instead of blood samples for noninvasive diagnosis.

There are several reports on the usefulness of diverting ileostomy for decreasing the incidence of anastomotic leakage and the severity of pelvic peritonitis. However, a number of complications induced by ileostomy itself have also been reported, including a special condition induced by obstruction at the outlet of the stoma known as “outlet obstruction.” In this study, we examined the frequency and risk factors of this complication based on the data of ileostomy cases in our institution. Methods: One hundred and seven patients who received ileostomy creation at our department from January 2010 to December 2015 were included. The incidence of outlet obstruction and risk factors were analyzed. Results: Outlet obstruction occurred in 18 cases (16.8%). The incidence was significantly higher in total colectomy or proctocolectomy cases as well as in those with left side construction and laparoscopic surgery than in other patients in a univariate analysis. However, in a multivariate analysis, no risk factors were extracted. Conclusions: To determine the true cause of this disease, a prospective study with a large number of cases is needed. Since multiple terms are used for this condition, resulting in confusion, a consensus on the appropriate terms is also important.