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Abstract Purpose Textbook outcome (TO) is a composite quality measurement of outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative resection for esophageal squamous cell carcinoma (ESCC) in elderly patients. Methods We retrospectively analyzed 105 patients who underwent curative esophagectomy for ESCC from 2005 to 2020. In accordance with previous reports, TO consisted of 10 parameters. The patients were divided into two groups: those who achieved TO (TO) and those who failed to achieve TO (non‐TO). We evaluated the association between TO and long‐term survival. Results TO was achieved in 28 (26%) patients. The patients in the TO group were significantly older (p = 0.02). The parameter with the lowest achievement rate was “No hospital stay ≥21 days”. The patients in non‐TO group had significantly shorter overall survival than those in TO group (p = 0.03). Multivariable Cox regression analyses of overall survival revealed that lymph node metastasis (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.73–6.78; p

Abstract Background The development and improved response to chemotherapy has resulted in a survival benefit of conversion surgery (CS) for advanced gastric cancer (GC). However, this benefit is limited in some cases, such as in those with very early recurrence (VER). This study investigated the relationship between outcome and clinicopathological characteristics after CS for stage IV GC, and the risk factors for VER after CS. Methods We retrospectively studied 184 patients with stage IV GC who initially underwent chemotherapy, including 36 patients who underwent CS between May 2007 and January 2022. We evaluated the long‐term outcome after CS for stage IV GC and the clinicopathological characteristics of the patients who underwent CS. Results Median survival times (MSTs) in the chemotherapy alone and CS groups were 13.4 and 36.5 months, respectively (p

Abstract Background Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results A high preoperative ECW/TBW was significantly associated with poorer relapse‐free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p

Abstract Background Chronic obstructive pulmonary disease (COPD) prevalence increases post‐esophagectomy morbidity. However, the association between COPD severity and post‐esophagectomy morbidity remains unclear because of the lack of an objective method to classify COPD severity. Low attenuation volume ratio (LAVR) estimated using Ziostation2 may reflect the extent of emphysematous changes in the lungs and COPD severity, thereby predicting post‐esophagectomy morbidity. Methods A total of 776 patients who underwent curative McKeown esophagectomy for esophageal cancer between April 2005 and June 2021 were included. The patients were divided into high and low preoperative LAVR groups. Short‐term outcomes between the groups were compared for patients who underwent open esophagectomy (OE) and minimally invasive esophagectomy (MIE). Results A total of 219 (28%) patients were classified into the high LAVR group. High LAVR was significantly associated with disadvantageous patient characteristics such as advanced age, heavy smoking, and impaired respiratory function. Patients with high LAVR had a significantly higher incidence of severe morbidity and pneumonia after OE. High LAVR was an independent risk factor for severe morbidity (odds ratio [OR], 2.52; 95% confidence interval [CI]: 1.237–5.143; p = 0.011) and pneumonia (OR, 2.12; 95% CI: 1.003–4.493; p = 0.049) after OE. Meanwhile, LAVR was not correlated with the incidence of post‐MIE morbidity. Conclusions LAVR may reflect COPD severity and predict severe morbidity and pneumonia after OE, but not after MIE. Less invasiveness of MIE may alleviate the effects of various disadvantageous backgrounds associated with high LAVR on worse short‐term outcomes.

Abstract Background Ehlers-Danlos syndrome is an inherited connective-tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Intestinal perforation is one of the fatal manifestations of this syndrome, and its management is complicated. Case presentation A 58-year-old woman with a familial history of Ehlers-Danlos syndrome visited the emergency department due to a sudden onset of lower abdominal pain. Plain abdominal computed tomography showed abdominal free air. We found a perforated descending colon and subsequently resected this lesion and performed ileostomy. Fifty-one days after this first operation, the patient had transverse colon perforation and thus underwent the Hartmann procedure as the second operation. In addition, she was diagnosed with small bowel perforation 53 days after the first operation and consequently underwent a third operation—partial resection of the jejunum with functional end-to-end anastomosis. Fifty-eight days after the first operation, she complained of acute abdominal pain. Plain abdominal computed tomography showed fluid collection near the jejunojejunal anastomosis. We detected dehiscence at the entry hole of the linear stapler during the operation and thus performed partial resection of the affected jejunum, followed by jejunostomy. The postoperative course of the fourth operation was uneventful. Genetic testing revealed a novel missense mutation (c.2095G>T, p.Gly699Cys) in the COL3A1 gene, which is presumed to be a pathogenic variant of vascular Ehlers-Danlos syndrome. Conclusion Vascular Ehlers-Danlos syndrome should be considered in the case of repeated intestinal perforation. The identified missense mutation in the COL3A1 gene (c.2095G>T, p.Gly699Cys) might be a novel pathogenic variation causing vascular Ehlers-Danlos syndrome. Careful postoperative screening and multidisciplinary management are required.

Abstract Background Preoperative treatment is performed for locally advanced colon cancer with extensive tumor proximity or suspected invasion of skeletal muscles, major organs, and blood vessels. Oxaliplatin-based regimens are often used in preoperative chemotherapy. However, microsatellite instability (MSI)-high colorectal cancer is often resistant to cytotoxic anticancer agents. Herein, we describe a case of treatment of anticancer drug-resistant MSI-high locally advanced colon cancer and review cases of complete response to immune checkpoint inhibitor therapy for colorectal cancer. Case presentation A 57-year-old woman was referred to our hospital with a large tumor in the descending colon and extensive thoracic and abdominal wall involvement, including the ribs and diaphragm. No distant metastasis was observed. The tumor had perforated the abdominal wall and formed an abscess. Upon visiting our hospital, emergency surgery was performed. An abdominal wall incision was made to drain the abscess and laparoscopic colostomy was performed. Histopathological examination of biopsy specimens revealed an adenocarcinoma with positive immunohistochemical expressions of both CDX2 and CK20. The patient was diagnosed with a descending colon cancer. Genetic examination found MSI-high, Kras mutation (F12G), and wild-type BRAF. After the inflammation improved, chemotherapy with the FOLFIRI regimen was initiated, but the tumor grew rapidly. As a second-line treatment, nivolumab and ipilimumab combination therapy was initiated. After four cycles of these therapies, the patient was administered nivolumab alone for five cycles. Tumor shrinkage was observed and radical surgery was performed. The patient underwent laparoscopic descending colon and partial thoracic and abdominal wall resection. The abdominal wall muscle was dissected from the abdominal cavity, and subcutaneous tissues, diaphragm, ribs were dissected from the body surface. Pathological examination revealed mucus components, fibrous tissues, and no malignant cells, indicating a complete pathological response (pCR). The patient had a good postoperative course and returned to work after being discharged. No recurrence was observed six months postoperatively. Conclusions Herein, we report a case of anticancer drug-resistant MSI-high colon cancer that was resected after treatment with immune checkpoint inhibitors, and a pCR was achieved. This new treatment strategy can be used for the treatment of cases that are not responsive to conventional therapies.

Abstract Background Sarcopenia is associated with poor prognosis in patients with colorectal cancer (CRC), but the mechanisms contributing to this association remain unclear. We hypothesized that skeletal muscle status is associated with tumor‐infiltrating lymphocytes (TILs) in patients with CRC. Therefore, this study investigated the clinical effect of sarcopenia and its relationship with the local immune system in CRC patients. Methods A total of 256 consecutive patients with CRC who underwent curative resection between 2008 and 2014 were enrolled. Sarcopenia was determined according to the skeletal muscle index (SMI), which was assessed using L3 skeletal muscle mass on axial computed tomography images, and its relationship with patient clinicopathological characteristics and survival was evaluated. Additionally, TILs (CD3+, CD8+, CD4+, and FOXP3+ T cells) were assayed by immunohistochemistry. The relationship between TILs and skeletal muscle status was evaluated. Results Patients with a lower SMI showed significantly shorter recurrence‐free and overall survival compared with those with a higher SMI. Low expression of TILs was associated with significantly shorter recurrence‐free survival. SMI was significantly correlated with the number of CD3+ and CD8+ cells in the ordinal logistic regression analysis. Patients with low skeletal muscle status and low CD3+ and CD8+ cells had an unfavorable prognosis compared with patients with high skeletal muscle status and high CD3+ and CD8+ cells. Conclusion Our data showed an association between skeletal muscle status and local immune cells, and this association may play a pivotal role in the clinical outcome of patients with CRC.

Abstract Aim Oncologic emergencies such as perforation and obstruction associated with colorectal cancer are serious diseases that can lead to sepsis. Peritoneal dissemination and other factors may cause cancer progression and worsen the patients’ long‐term prognosis. In this study, we investigated the effect of colorectal cancer presenting as oncologic emergencies on the patients’ clinical course. Methods We performed a retrospective study that included 448 patients with colorectal cancer who underwent primary resection at our institution between January 2014 and December 2018. The primary outcome was overall survival, while secondary outcomes were 30‐day mortality and postoperative complications. Cox regression was used to estimate the hazard ratio (HR) for overall survival. Results We identified 56 patients who presented with oncologic emergencies (OE group) and 392 patients who presented with no emergencies (NE group). Propensity‐score matching yielded 56 patients in the OE group and 55 in the NE group with balanced baseline covariates. We found a strong association between overall survival (OS) and oncologic emergencies (HR = 2.4; 95% confidence interval [CI], 1.1‐5.5). The 30‐day mortality was not significantly different between the OE and NE groups (4% vs 0%, P = .25). The incidence of severe postoperative complications (Clavien‐Dindo classification ≥grade 3) did not differ significantly between the groups (25% vs 15%, P = .23). Conclusion Colorectal cancer presenting as an oncologic emergency could be safely operated on without increasing the 30‐day mortality rate and the incidence of severe postoperative complications. However, the long‐term prognosis was poor.

Abstract Background A variety of factors for short‐ and long‐term outcomes have been reported after radical resection for gastric cancer (GC). Obesity and emaciation had been reported to be a cause of poor short‐ and long‐term outcomes with gastrointestinal cancer. However, the indicators are still controversial. The purpose of this study was to evaluate the relationship between perirenal thickness (PT) and short‐ and long‐term outcomes after radical surgery for GC. Methods We analyzed the data of 364 patients with GC who underwent radical surgery. We evaluated the distance from the anterior margin of the quadratus lumborum muscle to the dorsal margin of the left renal pole using computed tomography (CT) as an indicator of PT. The association between PT and clinicopathological factors and short‐ and long‐term outcomes was evaluated. Results The PT data were divided into low, normal, and high groups by gender using the tertile value. We found that the PT low group was 121 patients, normal group was 121 patients, and high group was 122 patients. Multivariate analyses showed that the high PT group was an independent risk factor for a short‐outcome after curative surgery in GC patients (odds ratio 2.163; 95% confidence interval [CI] 1.156–4.046; P = .016). And the low PT group was an independent risk factor for overall survival (hazard ratio 2.488; 95% CI 1.400–4.421; P = .0019) and relapse‐free survival (hazard ratio 2.342; 95% CI 1.349–4.064; P = .0025) after curative surgery in GC patients. Conclusion Perirenal thickness is a simple and useful factor for predicting short‐ and long‐term outcomes after radical surgery for GC.

Abstract Background Gastric cancer is relatively prone to metastasis, although distant metastasis is rare during the early stage of disease. Here we report a rare case of schwannoma-associated Virchow metastasis of a patient with early-stage gastric cancer. Case presentation A 73-year-old man, diagnosed with early-stage gastric cancer, underwent preoperative scrutiny, and was only suspected to have Virchow metastasis. Owing to atypical metastatic findings, a lymph node biopsy was performed to confirm the diagnosis and to determine the treatment strategy. The pathology results of the biopsy showed a diagnosis of schwannoma, the patient was judged to be surgically resectable, and a laparoscopic gastrectomy was performed to achieve a radical resection. The patient is currently under outpatient observation with no apparent recurrence. Conclusion Systemic chemotherapy is generally administered according to the physician’s clinical judgment, although the results of a lymph node biopsy contribute to a more curative treatment. When nonspecific metastases are found, it is important to make a reliable diagnosis and to select a treatment that achieves a cure.

Abstract The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti‐tumor necrosis factor‐α agents, but not with immunomodulators, anti‐integrin agents, and 5‐aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono‐S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short‐term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow‐up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta‐analyses from 2020‐2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.

Abstract Background Brain metastasis of colorectal cancer is infrequent, and isolated brain metastases are more infrequent. Thus, when neurological symptoms, such as paralysis or disturbance of consciousness appear, there is a high probability that the cancer has spread to other organs. Case presentation Here, we present a 64-year-old man with a progressive headache, decreased motivation, and aphasia who was diagnosed with a brain tumor in the left frontal region. He underwent a craniotomy, and the brain tumor was diagnosed as adenocarcinoma. We performed a colonoscopy and diagnosed rectal cancer without other distant metastases. After whole-brain radiotherapy (WBRT), low anterior resection for primary rectal tumor was performed using a robotic system. The patient was discharged in good condition and received postoperative adjuvant therapy for rectal cancer. He showed no signs of recurrence after 1 year of follow-up. Conclusions We described a rare case of rectal cancer that was diagnosed after resection of isolated brain metastasis. A good prognosis was achieved with surgery and WBRT.

Abstract Background The advanced lung cancer inflammation index (ALI), which comprehensively evaluates the patient body composition and inflammation/nutritional status, is reportedly associated with the patient outcome in lung cancer. However, the clinical significance in colorectal cancer (CRC) patients after curative resection remains unclear. Methods A total of 813 CRC patients after curative resection between April 2005 and June 2019 in a single institution were retrospectively enrolled. The association of the preoperative ALI (calculated as follows: body mass index × albumin value/neutrophil‐to‐lymphocyte ratio) with clinicopathological factors, postoperative complications, and survival was analyzed. Results A low ALI was significantly associated with male gender, older age, a higher depth of tumor invasion, progressed TNM stage, and preoperative carcinoembryonic antigen (CEA) positivity. Both postoperative complications and severe complications occurred more frequently in the ALI‐low group than in the ALI‐high group (P

Abstract Aim This study aimed to investigate the prognosis after recurrence in patients with stage I–III colon cancer (CC) and rectal cancer (RC). Methods Cancer recurred in 116 (15.2%) out of 763 patients with stage I–III colorectal cancer. The overall survival (OS) after recurrence was evaluated based on the recurrence organs and patterns. Results The first recurrence occurred in the lungs, livers, lymph nodes, and other sites in 32, 22, 12, and 2 patients, respectively. It was localized, disseminated, and involved two or more organs in 14, 9, and 25 patients, respectively. Patients with CC had a shorter OS after recurrence as compared to those with RC (P = .0103). Compared to other organ metastasis, liver metastasis was associated with an earlier recurrence (P = .0026) and shorter OS after recurrence (hazard ratio [HR]: 2.216; 95% confidence interval [CI]: 1.052–4.459; P = .0370). Lung metastasis was associated with a more favorable prognosis as compared to other organ recurrences (HR: 0.338; 95% CI: 0.135–0.741; P = .0057). One‐organ recurrence and oligometastasis were observed in 78.4% and 49.1% of the patients, respectively. The 5‐y OS rates of patients with one‐organ recurrence and oligometastasis were 47.5% and 71.7%, respectively. Invasive treatment was associated with a favorable prognosis (P

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 The adapted systemic inflammation score (aSIS), calculated from serum albumin and the lymphocyte‐to‐monocyte ratio, has been reported to be a novel prognostic marker for some types of cancers. However, the prognostic impact of aSIS in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to examine the prognostic effects of aSIS in a large cohort of 509 ESCC patients. Methods Preoperative aSIS was retrospectively calculated for 509 ESCC patients who underwent curative resection. Time‐dependent receiver operating characteristics (t‐ROC) curves were used for comparing the prognostic impact. Results Patients with high aSIS showed significantly poorer overall survival (OS) than patients with low aSIS (log rank P

Objective:. This comprehensive analysis aimed to elucidate the mechanism underlying how high pretreatment red blood cell distribution width (RDW) reflects poor prognosis after esophagectomy for esophageal cancer. Background:. Several cohort studies have reported that preoperative RDW might be a predictive marker for poor prognosis after esophagectomy; however, the underlying mechanism of this relationship has not been elucidated. Methods:. This study included 626 patients with esophageal cancer who underwent esophagectomy between April 2005 and November 2020. A retrospective investigation of the association between pretreatment RDW and clinicopathological features, blood data, short-term outcomes, and prognosis was conducted using a prospectively entered institutional clinical database and the latest follow-up data. Results:. Of 626 patients, 87 (13.9%) had a high pretreatment RDW. High RDW was significantly associated with several disadvantageous characteristics regarding performance status, the American Society of Anesthesiologists physical status, respiratory comorbidity, and nutritional status. Similarly, high RDW correlated with frequent postoperative morbidities (respiratory morbidity and reoperation; P = 0.022 and 0.034, respectively), decreased opportunities for adjuvant chemotherapy (P = 0.0062), and increased death from causes other than esophageal cancer (P = 0.046). Finally, RDW could be an independent predictor of survival after esophagectomy (hazard ratio, 1.47; 95% confidence interval, 1.009–2.148; P = 0.045). Conclusion:. High pretreatment RDW reflected various adverse backgrounds and it could be a surrogate marker of poor prognosis in patients who have undergone esophagectomy for esophageal cancer.

Objective:. To establish the prognostic value of mean corpuscular volume (MCV) in patients with esophageal squamous cell carcinoma (ESCC) who have undergone esophagectomy. Background:. The MCV increases in patients with high alcohol and tobacco consumption. Such a lifestyle can be a risk factor for malnutrition, comorbidities related to those habits, and multiple primary malignancies, which may be associated with frequent postoperative morbidity and poor prognosis. Methods:. This study included 1673 patients with ESCC who underwent curative esophagectomy at eight institutes between April 2005 and November 2020. Patients were divided into normal and high MCV groups according to the standard value of their pretreatment MCV. Clinical background, short-term outcomes, and prognosis were retrospectively compared between the groups. Results:. Overall, 26.9% of patients had a high MCV, which was significantly associated with male sex, habitual smoking and drinking, multiple primary malignancies, and malnutrition, as estimated by the body mass index, hemoglobin and serum albumin values, and the Geriatric Nutritional Risk Index. Postoperative respiratory morbidity (P = 0.0075) frequently occurred in the high MCV group. A high MCV was an independent prognostic factor for worse overall survival (hazard ratio, 1.27; 95% confidence interval, 1.049–1.533; P = 0.014) and relapse-free survival (hazard ratio, 1.23; 95% confidence interval, 1.047–1.455; P = 0.012). Conclusions:. A high MCV correlates with habitual drinking and smoking, malnutrition, and multiple primary malignancies and could be a surrogate marker of worse short-term and long-term outcomes in patients with ESCC who undergo esophagectomy.

Abstract Aim This study investigated whether preoperative serum transferrin, a rapid‐turnover protein, was associated with prognosis after colorectal cancer (CRC) resection. Methods We evaluated preoperative transferrin, which was calculated as iron and unsaturated iron‐binding capacity, in 501 patients who underwent surgery for Stage I–III CRC. Transferrin level was directly proportional to total iron‐binding capacity (TIBC), and TIBC

We have developed 12-membered silica-tetrahedra-ringed Na5YSi4O12-type sodium ion conducting glass-ceramics on the basis of the composition Na3+3x-yR1-xPySi3-yO9 (R: rare earth elements; denoted as Narpsio); especially, the material of Na4Y0.6P0.2Si2.8O9 with the combined parameters of (x, y) = (0.4, 0.2) gives rise to the maximum conductivity of 1 × 10−1 Scm−1 at 300 °C. Because glass-ceramics generally have the advantage of structural rigidity and chemical durability over sintered polycrystalline ceramics, the present study employed glass-ceramic Narpsio to perform chemically driven ion exchange of Na+ with protonated water molecules with an aim to produce a proton conductor. The ion exchange was carried out in a hydrochloric acid solution by changing immersion time, temperature, and acid concentration. The ion exchanged Na4Y0.6P0.2Si2.8O9-based glass-ceramics were analyzed by the complex impedance method, and the proton conductivity was found to exhibit 3 × 10−4 Scm−1 at 300 °C with the activation energy of 59 kJ/mol. The dependence of humidity-sensitive conductivity of the ion exchanged bulk glass-ceramics was also examined; the conductivity increased almost linearly from 0.6 × 10−4 Scm−1 in dry air to 1.5 × 10−4 Scm−1 in 75% humid ambience at 300 °C. Thus, the ion exchanged glass-ceramics can be considered to be high temperature proton conductors as well as humidity sensors.

Abstract Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of 6.9/100 000. They arise from cells of the diffuse endocrine system, which are mainly dispersed throughout the gastrointestinal (GI), pancreatic, and respiratory tracts. The incidence of GI‐NETs has recently begun to show a steady increase. According to the Surveillance, Epidemiology, and End Results database, 53% of patients with NETs present with localized disease, 20% with locoregional disease, and 27% with distant metastases at the time of diagnosis. Surgery is the mainstay for the treatment of locoregional GI‐NETs. Endoscopic resection is an option for well‐differentiated early GI‐NETs, which are thought to very rarely metastasize to lymph nodes. A lesion that is technically difficult to resect via endoscopy is an indication for local resection (partial resection without lymph node dissection). GI‐NETs with possible lymph node metastasis is an indication for enterectomy with lymph node dissection. For NETs with metastatic lesions, cytoreduction surgery can control hormonal hypersecretion and alleviate symptoms; therefore, cytoreduction surgery is recommended. The indications for surgery vary and are based on the organ where the NET arose; therefore, an understanding of the patient's clinical state and individualized treatment that is based on the characteristics of the patient's GI‐NET is needed. This review summarizes surgical treatments of GI‐NETs in each organ.

Mini-abstract:. The pan-immune-inflammation value was associated with clinical outcomes and tumor-infiltrating lymphocytes in 866 esophageal cancers. Systemic immune competence may influence patient prognosis through local immune response. Objective:. To examine the relationship between the pan-immune-inflammation value (PIV), tumor immunity, and clinical outcomes in 866 patients with esophageal cancer. Background:. The PIV, calculated from all immune-inflammatory cells in the peripheral blood count, is a recently proposed marker for clinical outcomes in some types of cancers. Nonetheless, the prognostic significance of PIV in esophageal cancer remains unclear. Methods:. In the derivation cohort (n = 433), we set the optimal cutoff value using a time-dependent receiver operating characteristic (ROC) curve. In the validation cohort (n = 433), the relationships between the PIV, tumor-infiltrating lymphocytes (TILs), CD8 expression by immunohistochemical staining, and patient prognosis were examined. Results:. The area under the ROC curve for the PIV at 5 years was 0.631 in the derivation cohort. The validation cohort, divided into PIV-low cases (n = 223) and PIV-high cases (n = 210), showed significantly worse overall survival (log-rank P = 0.0065; hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.12–1.98; P < 0.001; multivariate HR: 1.41; 95% CI: 1.05–1.90; P = 0.023). The prognostic effect of the PIV was not significantly modified by any clinical characteristics (P for interaction > 0.05). The PIV-high cases were significantly associated with a low TIL status (P < 0.001) and low CD8-positive cell counts (P = 0.011). Conclusions:. The PIV was associated with clinical outcomes in esophageal cancer, supporting its role as a prognostic biomarker. Considering the relationship between the PIV and TILs, systemic immune competence may influence patient prognosis through a local immune response.

Abstract The classification of colorectal cancer (CRC) plays a pivotal role in predicting a patient's prognosis and determining treatment strategies. The consensus molecular subtype (CMS) classification system was constructed by analyzing genetic information from 18 CRC data sets, containing 4151 CRC samples. CRC was classified into four subtypes with distinct molecular and biological characteristics: CMS1 (microsatellite instability immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). Since their designation in 2015, these classifications have been applied to basic and translational research of CRC, with the hope that understanding these subsets will influence a clinician's approach to therapeutic treatment and improve clinical outcomes. We reviewed CRC investigations in accordance with CMSs published in the last 5 years to further explore the clinical significance of these subtypes and identify underlying trends that may direct relevant future research. We determined that CMSs linked common features of CRC cell lines and PDX models in various studies. Furthermore, associations between prognosis and clinicopathological findings, including pathological grade and the stage of carcinogenesis, tumor budding, and tumor location, were correlated with CMS classification. Novel prognostic factors were identified, and the relationship between chemotherapeutic drug resistance and CMS has been fortified by our compilation of research; thus, indicating that this review provides advanced insight into clinical questions and treatment strategies for CRC.

Abstract Pulmonary morbidity is the most common complication after esophagectomy. Importantly, it is the main cause of surgery‐related mortality and possibly adversely affects the long‐term outcome after surgery in patients with esophageal cancer. There is considerable accumulated evidence on multidisciplinary approaches to reduce post‐operative pulmonary morbidity. A comprehensive review of the precautionary measures that have so far been shown to be effective in previous literature is of utmost importance. We herein update and summarize the perioperative and surgical approaches to diminish pulmonary morbidity. Pre‐operative smoking cessation, respiratory rehabilitation, maintaining oral hygiene, perioperative nutritional intervention, enforcement of less invasive surgery, perioperative administration of steroid, and total management by a multidisciplinary team could be the key factors contributing to reduction in pulmonary morbidity.

Abstract Background Advancements in chemotherapy for metastatic colorectal cancer (mCRC) have improved long-term outcomes, and median survival currently exceeds 30 months. The recommended treatment for mCRC is multidisciplinary, including a combination of surgical resection and chemotherapy. In this study, we report the case of a patient who has survived for more than 5 years after an initial diagnosis of mCRC while undergoing first-line chemotherapy and six repeat metastasectomies. Case presentation A 55-year-old man was diagnosed at our hospital with sigmoid colon cancer and hepatic metastasis. We performed laparoscopic sigmoidectomy and hepatic segmentectomy (segment 5 [S5] and S8). After resecting the primary tumor and liver metastasis, other metastases were found. Together with perioperative chemotherapy (CAPOX + bevacizumab), we performed repeated metastasectomies for liver metastasis (S4 and S7), pulmonary S1 metastasis, aortic lymph node metastasis, and right adrenal metastasis. With six metastasectomies, the patient has survived for more than 5.5 years. Conclusions Multidisciplinary treatment extends survival and improves the quality of life in patients with mCRC. Planned surveillance after metastasectomy may also be necessary to promote the early detection of recurrence in these patients.

Abstract Background IgG4-related disease (IgG4-RD) is an immune-mediated disorder in which abundant IgG4-positive plasma cells infiltrate affected organs. There have been reported four cases of probable IgG4-RD presenting as a submucosal tumor of the stomach. We herein report the first case of definite IgG4-RD presenting as a submucosal tumor of the stomach resected with laparoscopic endoscopic cooperative surgery (LECS). Case presentation A 70-year-old woman with a 6-year history of autoimmune pancreatitis was referred to our department because a 15-mm submucosal tumor in the greater curvature of the lower part of the stomach had been identified via upper gastrointestinal endoscopy. Endoscopic ultrasonography showed a 10-mm low-echoic lesion derived from the submucosal layer of the stomach. A fine-needle aspiration biopsy was attempted, but the tumor was too hard for sampling. F-fluorodeoxyglucose (FDG) positron emission tomography showed an FDG uptake, suggesting a possibility of malignant disease. As the diagnosis could not be confirmed, LECS for both the diagnosis and curative treatment was performed. A histopathological examination showed a tumor with IgG4-positive lymphoplasmacytic infiltration and fibrosis. The ratio of IgG4+/IgG+ lymphoplasmacytic cells was > 80%. A laboratory examination showed elevation of the serum IgG4 levels preoperatively. Thus, the final diagnosis was IgG4-RD of the stomach. No recurrence was observed within 1 year after surgery. Conclusions We encountered a case of definite IgG4-RD presenting as a gastric SMT in which a correct diagnosis was achieved by a minimally invasive LECS technique. IgG4-RD may present as a gastric lesion and should be taken into consideration as a differential diagnosis.

Abstract Background Port site recurrence has been observed after a variety of oncologic resection procedures. However, few have reported port site recurrence of esophageal cancer. Case presentation A 51-year-old man underwent minimally invasive esophagectomy for pT3(AD)N3M0 adenocarcinoma of the esophagus. One year after surgery, he presented with a rapidly growing tumor on the right thoracic wall. Contrast computed tomography demonstrated an enhancing tumor with uptake on positron emission tomography. We performed resection of the thoracic wall, including the skin and subcutis. The pathologic diagnosis was poorly differentiated adenocarcinoma, consistent with metastasis of esophageal origin. Conclusion This was the first report on thoracic port site recurrence of esophageal adenocarcinoma. We recommend elimination of leakage around the thoracoscopic ports to prevent such recurrence. We should provide prudent postoperative clinical surveillance.

Abstract Background The recurrence of endoscopically resected intramucosal colorectal cancer (CRC) is quite rare, and data regarding metastasis in intramucosal tumors are still lacking. We herein report a case of presacral lymph node recurrence of intramucosal rectal cancer after curative endoscopic resection. Case presentation A 53-year-old man underwent endoscopic mucosal resection (EMR) for rectal intramucosal adenocarcinoma. Thirty-nine months after the procedure, follow-up computed tomography (CT) revealed a swollen anterior sacral lymph node with an abnormal fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). He underwent laparoscopic low anterior resection (LAR) and was discharged on postoperative day 11 without any complications. The pathological examination confirmed solitary lymph node metastasis (moderately differentiated adenocarcinoma) without a residual tumor in the rectal epithelium. We diagnosed him with lymph node metastasis of rectal cancer. Pathological examination of the resected lymph node confirmed moderately differentiated adenocarcinoma. He has not experienced any re-recurrence in the 6 months since surgery. Conclusions This is a rare case of local lymph node recurrence of intramucosal rectal cancer after successful EMR that was salvaged with surgery. Surveillance after successful endoscopic resection of rectal cancer using both endoscopy and CT is necessary.

Abstract Background To date, only a few cases of multiple GISTs with different clones in different organs have been published. However, a case of multiple GISTs with different clones occurring in a single organ has never been reported. Case presentation A 41-year-old patient underwent laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST) in 2012. The pathological findings showed high-risk characteristics for recurrence, so he received adjuvant therapy with imatinib for 3 years. In 2018, 3 years after completing the adjuvant therapy, tumor lesions at residual gastric cardia were incidentally identified by follow-up computed tomography (CT). The pathological findings of the tumor biopsy revealed gastric GIST. He underwent secondary laparoscopic partial gastrectomy and was diagnosed with high-risk GIST. Adjuvant therapy with imatinib was restarted immediately. The two gastric GISTs had the same exon 11 mutations in the c-kit gene, but they had different missense mutations. This molecular heterogeneity suggested that they were derived from different origins. Conclusion We reported a multiple heterochronic GIST in the stomach detected 6 years after resection. There may be a possibility that another heterochronic GIST will occur in the remnant stomach in the future, so close follow-up will be needed.

Abstract Background The incidence of synchronous gastrointestinal neuroendocrine tumors (GI-NETs) and colorectal cancer is very low. Case presentation We present a 72-year-old man diagnosed with a rectal neuroendocrine tumor (NET) with multiple organ metastases and simultaneous sigmoid colon cancer. Although the NET was his prognostic factor, he underwent a laparoscopic sigmoidectomy at first because it was expected that the colon cancer would cause obstruction or bleeding during NET treatment. Subsequently, he started taking everolimus. Conclusions We should consider surgical resection of the synchronous cancer before systemic therapy for a GI-NET regardless of the difference in prognosis between synchronous tumors, if the cancer may impair the continuation of systemic therapy.

Abstract Background Persistent descending mesocolon (PDM) is caused by the absence of fusion of the descending colon to the retroperitoneum. We herein report two colorectal cancer cases with PDM that were treated with laparoscopic surgery. Case presentation Case 1: a 50-year-old man with sigmoid colon cancer and synchronous liver metastasis. After neoadjuvant chemotherapy, he underwent laparoscopic sigmoidectomy with lymph node dissection cutting the root of the inferior mesenteric artery (IMA) and synchronous liver resection. He experienced postoperative stenosis of the reconstructed colon possibly due to an impaired arterial blood flow in the reconstructed colon. Case 2: a 77-year-old man with rectal cancer. Laparoscopic low anterior resection preserving the left colic artery (LCA) was performed. Intraoperative infrared ray (IR) imaging using indocyanine green (ICG) showed good blood flow of the reconstructed colon. He had no postoperative complications. In cases of PDM, the mesentery of the descending and sigmoid colon containing the LCA is often shortened, and the marginal artery of the reconstructed colon is located close to the root of the LCA. Lymph node dissection accompanied by cutting the LCA carries a risk of marginal artery injury. Therefore, we recommend lymph node dissection preserving the LCA in colorectal cancer patients with PDM in order to maintain the blood flow of the reconstructed colon. If the IMA and LCA absolutely need to be cut for complete lymph node dissection, the marginal artery should be clearly identified and preserved. In addition, intraoperative IR imaging is extremely useful for evaluating colonic perfusion and reducing the risk of anastomotic complications. Conclusion In colorectal cancer surgery in patients with PDM, surgeons should be aware of these tips for maintaining the blood flow of the reconstructed colon and thereby avoid postoperative complications caused by an impaired blood flow.

Abstract Background The incidence of metastatic spread of gastrointestinal malignancies to the thyroid gland is relatively low and most of these malignancies originate from the colorectum. Thyroid metastasis originating from the esophagus is poorly documented. Case presentation A 79-year-old man presented with hoarseness of voice and swallowing difficulty. Eighteen months earlier, he had undergone preoperative chemotherapy (S-1 and oxaliplatin [SOX] therapy) and subtotal esophagectomy with regional lymph nodes dissection and retrosternal narrow gastric tube reconstruction for advanced Barrett’s esophageal adenocarcinoma. In the ultrasonographic examination, there was a hypoechoic, indistinct border and heterogeneous nodule in the left lobe of the thyroid gland. Pathological examination of an ultrasound-guided fine-needle aspiration showed adenocarcinoma, supporting a diagnosis of esophageal adenocarcinoma metastases in the thyroid. Conclusion This is a first case of a patient with thyroid metastasis from Barrett’s esophageal adenocarcinoma after subtotal esophagectomy.

Summary: In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression and chemoresistance. However, the role of senescent CAFs in metastatic lesions and the molecular mechanism of inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains the SASP by demethylating H3K27me3 marks in CAFs and enhances peritoneal tumor formation of gastric cancer (GC) through JAK/STAT3 signaling in a mouse model. A JAK/STAT3 inhibitor blocks the increase in GC cell viability induced by senescent CAFs and peritoneal tumor formation. Single-cell mass cytometry revealed that fibroblasts exist in the ascites of GC patients with peritoneal dissemination, and the fibroblast population shows p16 expression and SASP factors at high levels. These findings provide insights into the inflammation-related SASP maintenance by histone modification and the role of senescent CAFs in GC peritoneal dissemination.

In order to clarify the ability of animals to communicate with humans, it is necessary to examine the behaviors of animals directed at humans, taking into account individual differences. This study investigated whether the behaviors of goats (Capra hircus) can be predicted when given an unsolvable task. Two experiments were performed in a paddock using 16 domesticated goats. In Experiment 1, behavioral tests were conducted to determine the goats’ social rank and reactivity toward a stranger. In Experiment 2, the goats’ behaviors in an unsolvable task and two control conditions in which either only a human or bucket was presented were examined. The behaviors of the goats were video-recorded and compared between the conditions. Then, we examined whether the behaviors of goats in the presence of both the human and unsolvable task can be predicted from the scores for social rank and reactivity toward humans. Compared with the control conditions, the goats increased physical contact with the human, but did not increase gazing. It is possible that differences in individual characteristics and long-term experiences with humans can lead to differences in human-directed behaviors of animals. Although the social rank order of the goats was clearly linear, there was no correlation between their behaviors in the unsolvable task and their social rank. The goats that tended to interact with the stranger in Experiment 1 were more likely to approach and establish contact with the human in the unsolvable task than goats that reacted more averse toward humans. There was no association between the level of reactivity toward the stranger and the goats’ involvements in the unsolvable task. Therefore, it is possible that the goats which increased interactions with humans did not necessarily have low motivation to engage in unsolvable tasks, but relied on humans as a means of communication. In conclusion, the behavioral changes and its diversity as the responses toward short-term changes in the environment, such as the presence or absence of humans and unsolvable tasks, were related to differences in individual behavioral characteristics (i.e., reactivity toward humans).

Abstract Background Primary colonic and dedifferentiated liposarcomas are both remarkably rare. This work describes a case of primary colonic well-differentiated/dedifferentiated liposarcoma and reviews the clinical characteristics and current therapies for liposarcoma tumors. Case presentation A 52-year-old woman was referred to our hospital with a submucosal tumor of the ascending colon. Clinical analysis by ultrasound colonoscopy and computed tomography revealed a partially ossified tumor with irregular edges continuous with the muscular layer. High F-18 deoxyglucose uptake was detected by positron emission tomography. Radical resection with lymph node dissection was performed, yielding a tumor specimen approximately 6.5 × 4.0 × 3.2 cm. Neoplastic spindle cell proliferation was found from submucosa to subserosa. Well-differentiated adipose tissue surrounded the tumor, but contained atypical nuclei with condensed chromosomes. Immunohistochemical staining was positive for p16, CDK4, and MDM2 expression. Based on these findings, a diagnosis of well-differentiated/dedifferentiated liposarcoma was given. Dedifferentiated liposarcomas are more aggressive than their well-differentiated, low-grade counterparts. While local recurrence can occur with both tumor types, dedifferentiated liposarcomas are more prone to developing distant metastases. The patient received no postoperative therapy, and no recurrences have been observed 12 months after surgery. Conclusions Here we report an extremely rare case of well-differentiated/dedifferentiated liposarcoma of the ascending colon. The dedifferentiated component was high-grade liposarcoma and well-differentiated liposarcoma was detected around the main tumor.

Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are implicated in various physiological processes. Unambiguous evidence indicates that dysregulation of ncRNAs is deeply implicated in carcinogenesis, cancer progression and metastases of various cancers, including ESCC. The current review summarizes recent findings on the ncRNA-mediated mechanisms underlying the characteristic behaviors of ESCC that will help support the development of biomarkers and the design of novel therapeutic strategies.

The Ag-nanoparticles (Ag-NP)/TiO2 composite thin films with various amounts of Ag (10 mol% ≤ n ≤ 80 mol%) were examined as a potential photocatalyst by decoloration reaction of methylene blue (MB) in an aqueous solution. These composite thin films of ca. 100 nm thickness were fabricated by the MPM at 600 °C in air. The decoloration rates monitored by the absorption intensity of the MB solution indicated that the composite thin films of Ag with an amount less than 40 mol% are not effective under vis-irradiation, though they can work as a photocatalyst under UV-irradiation. Further, the UV-sensitivity of the composite thin films gradually decreased to almost half the level of that of the TiO2 thin film fabricated under the identical conditions when the Ag amount increased from 10 to 40 mol%. Contrarily, the composite thin films of Ag content larger than 50 mol% showed the vis-responsive activity, whose level was slightly lower than the decreased UV-sensitivity. Diffuse reflectance spectra suggested that the vis-responsive activity of the composite thin films is due to the conductivity, localized surface plasmon resonance and surface plasmon resonance of Ag-NP. It was also elucidated that the vis-responsive level of the composite thin films corresponds to their electrical conductivity that depends on the Ag content.

Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194-3.619; p = 0.010) was independently associated with OS.Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC.