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Numerous biomarkers that reflect host status have been identified for patients with metastatic colorectal cancer (mCRC). However, there has been a paucity of biomarker studies that comprehensively indicate body composition, nutritional assessment, and systemic inflammation status. The advanced lung cancer inflammation index (ALI), initially introduced as a screening tool for patients with non-small-cell lung cancer in 2013, emerges as a holistic marker encompassing all body composition, nutritional status, and systemic inflammation status. The index is calculated by the simple formula: body mass index × albumin value / neutrophil-to-lymphocyte ratio. Given its accessibility in routine clinical practice, the ALI has exhibited promising clinical utility in prognosticating outcomes for patients with multiple types of cancer. In this review, we focus on the significance of host status and the clinical applicability of the ALI in the treatment and management of patients with malignancies, including mCRC. We also suggest its potential in guiding the formulation of treatment strategies against mCRC and outline future perspectives.

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.

Mycobacterium avium complex (MAC) is a non-tuberculous mycobacterium widely distributed in the environment. Even though MAC infection is increasing in older women and immunocompromised patients, to our knowledge there has been no comprehensive analysis of the MAC-infected host-cell transcriptome—and particularly of long non-coding RNAs (lncRNAs). By using in vitro-cultured primary mouse bone-marrow-derived macrophages (BMDMs) and Cap analysis of gene expression, we analyzed the transcriptional and kinetic landscape of macrophage genes, with a focus on lncRNAs, during MAC infection. MAC infection of macrophages induced the expression of immune/inflammatory response genes and other genes similar to those involved in M1 macrophage activation, consistent with previous reports, although Nos2 (M1 activation) and Arg1 (M2 activation) had distinct expression profiles. We identified 31 upregulated and 30 downregulated lncRNA promoters corresponding respectively to 18 and 26 lncRNAs. Upregulated lncRNAs were clustered into two groups—early and late upregulated—predicted to be associated with immune activation and the immune response to infection, respectively. Furthermore, an Ingenuity Pathway Analysis revealed canonical pathways and upstream transcription regulators associated with differentially expressed lncRNAs. Several differentially expressed lncRNAs reported elsewhere underwent expressional changes upon M1 or M2 preactivation and subsequent MAC infection. Finally, we showed that expressional change of lncRNAs in MAC-infected BMDMs was mediated by toll-like receptor 2, although there may be other mechanisms that sense MAC infection. We identified differentially expressed lncRNAs in MAC-infected BMDMs, revealing diverse features that imply the distinct roles of these lncRNAs in MAC infection and macrophage polarization.

Abstract Aims Mismatch‐repair deficiency and microsatellite instability‐high (dMMR/MSI‐H) colorectal cancer (CRC) is treated with programmed death (PD)‐1 antibody regardless of PD‐ligand (L)1 expression in tumor cells. We previously found that abundant CD169+ macrophages in regional lymph node (RLN) sinuses and CD8+ tumor‐infiltrating lymphocytes (TILs) positively correlated in CRC and were associated with a favorable prognosis. However, associations between dMMR/MSI‐H CRC and CD8+ TILs or prognoses vary among studies. In this study, we attempted to compare the association between MMR status, CD169+ macrophages in RLNs, CD8+ TILs, PD‐L1 scores, and prognoses in CRC. Methods and Results We immunostained 83 surgically resected CRC tumors that we previously analyzed for MMR proteins, and identified 9 that were dMMR. The number of CD169+ macrophages in RLNs and CD8+ TILs significantly correlated with overall survival, whereas MMR status did not. The number of cells positive for the TIL markers CD3, CD4, CD8, and TIA‐1, and macrophage markers CD68 and CD169 in RLNs did not significantly differ between groups according to MMR status. Furthermore, combined positive scores (CPS) for PD‐L1 expression in five of nine dMMR CRCs were all

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.

Background & Aims: Hepatocellular carcinoma (HCC) mainly develops from chronic hepatitis. Metabolic dysfunction-associated steatohepatitis (MASH) has gradually become the main pathogenic factor for HCC given the rising incidence of obesity and metabolic diseases. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin 2 (PGE2), which is known to exacerbate inflammatory responses. However, the role of PGE2 accumulation caused by 15-PGDH downregulation in the development of MASH-HCC has not been determined. Methods: We utilised the steric animal model to establish a MASH-HCC model using wild-type and 15-Pgdh+/− mice to assess the significance of PGE2 accumulation in the development of MASH-HCC. Additionally, we analysed clinical samples obtained from patients with MASH-HCC. Results: PGE2 accumulation in the tumour microenvironment induced the production of reactive oxygen species in macrophages and the expression of cell growth-related genes and antiapoptotic genes. Conversely, the downregulation of fatty acid metabolism in the background liver promoted lipid accumulation in the tumour microenvironment, causing a decrease in mitochondrial membrane potential and CD8+ T-cell exhaustion, which led to enhanced development of MASH-HCC. Conclusions: 15-PGDH downregulation inactivates immune surveillance by promoting the proliferation of exhausted effector T cells, which enhances hepatocyte survival and proliferation and leads to the development of MASH-HCC. Impact and implications: The suppression of PGE2-related inflammation and subsequent lipid accumulation leads to a reduction in the severity of MASH and inhibition of subsequent progression toward MASH-HCC.

Abstract Since the advent of immune checkpoint inhibitors, which modulate the interplay between the tumor cell and immune system, immunotherapy has become widely recognized as a new standard treatment for cancers including microsatellite instability‐high (MSI‐H) colorectal cancer. Immune checkpoint inhibitors such as pembrolizumab and nivolumab (anti‐PD‐1 antibodies) that act in the effector phase of T cells and ipilimumab (anti‐CTLA‐4 antibody) that acts mainly in the priming phase are now in clinical use. These antibodies have shown therapeutic efficacy in MSI colorectal cancer patients who have failed to respond to existing standard therapies. Pembrolizumab is also strongly recommended as first‐line therapy for MSI‐H metastatic colorectal cancer. Therefore, the MSI status and tumor mutation burden of the tumor should be clarified before starting treatment. Because many patients do not respond to immune checkpoint inhibitors, combination therapies with immune checkpoint inhibitors, including chemotherapy, radiotherapy, or molecularly targeted agents, are being investigated. Furthermore, treatment methods for preoperative adjuvant therapy for rectal cancer are being developed.

Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.

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.

Objectives: Leprosy, or Hansen's disease was a major public health problem in Japan in the early 20th century. Today, the number of new cases has decreased significantly. We aimed to investigate the trends of leprosy in Japan over the past 73 years and the challenges faced in recent years. Methods: We assessed the data on newly registered cases of leprosy from 1947 to 2020. Results: A total of 10,796 newly registered cases of leprosy were reported during the study period, of which 7573 were registered in mainland Japan, 2962 in Okinawa, and 250 were of foreign origin. Most autochthonous cases were born before 1950 in mainland Japan and before 1975 in Okinawa. The number of nonautochthonous cases surpassed that of autochthonous cases in 1992. Nonautochthonous cases originated from 26 countries, particularly Brazil and the Philippines. Three cases of antimicrobial resistance have been detected among nonautochthonous cases since 2004. Conclusion: Our data suggest that ongoing transmission of leprosy likely ceased in the 1940s in mainland Japan and in the 1970s in Okinawa. With the recent rise of nonautochthonous cases with globalization, continuous surveillance and efforts to maintain leprosy services within the country are necessary even after reaching the state of elimination.

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 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.

Background/Aim: Although chemotherapy for colorectal cancer has advanced remarkably, long-term chemotherapy can lead to a variety of infections. However, if chemotherapy must be discontinued to control infection, there is a risk of progression of colorectal cancer. Intracranial subdural empyema is a life-threatening intracranial infection. The condition requires 6-8 weeks of antibiotic therapy, and the patient must discontinue chemotherapy during treatment. We herein present a case of intracranial subdural empyema during long-term chemotherapy for metastatic rectal cancer. Case Report: A 69-year-old woman with unresectable metastatic rectal cancer had a convulsive seizure and was admitted to our hospital. The cause of the convulsive seizure was considered a metastatic brain tumor from rectal cancer. However, on the basis of contrast-enhanced computed tomography and contrastenhanced magnetic resonance imaging, we diagnosed intracranial subdural empyema. The infection was controlled by antibiotics, but chemotherapy for rectal cancer was discontinued during antibiotic treatment. As a result, the rectal cancer progressed, and the patient died 65 days after admission to our hospital. Conclusion: Intracranial subdural empyema may develop rarely during chemotherapy. This condition requires long-term treatment with antibiotics; therefore, early detailed imaging and diagnosis may improve the prognosis. [ABSTRACT FROM AUTHOR]

To predict the failure of mechanical parts, it is necessary to understand the residual stress and its source, i.e., inherent strain. In this study, the distribution of three-directional residual stress components in a carburized 18NiCrMo14-6 cylindrical roller test piece with a diameter of 80mm and length of 240 mm, was measured using the extended contour method (XCM), which combines the contour method and X-ray diffraction. Thereafter, an inverse analysis was applied to the measured residual stress to reproduce the associated inherent strain distribution. First, it was shown through numerical experiments of a carburized cylindrical specimen that the distribution of the three-directional residual stress components can be accurately reproduced using XCM. Next, it was demonstrated that the distribution of the three-directional residual stress components could be obtained using general-purpose equipment by physically measuring the same type of specimen. The inherent strain distributions were evaluated. Compressive residual stress and corresponding tensile inherent strain were detected in the carburized layer. By contrast, tensile stress and inherent contraction strain were determined in the non-carburized layer just before the carburized crust. Finally, the mechanism of inherent strain generation was investigated using a thermal--elastic--plastic analysis. Possible explanations include (i) increase in transformation strain due to a change in carbon content, (ii) delay in martensitic transformation, and (iii) decrease in the martensitic transformation rate due to a decrease in the cooling rate at the core. [ABSTRACT FROM AUTHOR]

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 In places prone to earthquakes, piles need to be designed to resist seismic damage. However, the characteristics of the soil significantly impact the seismic resistance of piles. Accordingly, in this study, shaking table tests and three‐dimensional finite element analyses were conducted to investigate the seismic response and nonlinear characteristics of pile‐soil springs of a structure supported by a pile group in granular soil on a sloping bedrock. The analytical experiments and simulation were conducted on a group of nine piles arranged in the shape of a square. The results showed that the constraint condition at the pile tip influenced the bending moment response of piles during large input motion, such as that observed during earthquakes. Furthermore, the pile location, direction of pile displacement, and depth was found to affect the influence of the sloping bedrock on the pile soil springs.

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 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.

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

Abstract Background A previous Phase I/II study demonstrated that TAS‐102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. Methods This is a multicenter, single‐arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression‐free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). Results Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70–88); the ECOG‐PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3–4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). Conclusions FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross‐resistance with 5‐fluorouracil. Clinical trial registration: UMIN clinical trials registry (UMIN000025241).

Abstract Colorectal cancer (CRC) is the most common cancer and the second leading cause of cancer death in Japan. Surgical resection is the only curative option for localized disease. However, undetectable micrometastases remaining after curative surgery may cause disease recurrence. Adjuvant chemotherapy aims to eradicate these micrometastases to improve the cure rate. Unfortunately, few reliable prognostic and predictive markers are available that identify patients at high risk for CRC during early‐stage disease. However, promising biomarkers may become available in the near future. Such biomarkers provide information for stratifying a patient's risk and for selecting the optimal treatment. Here, we provide an overview of current relevant prognostic and predictive biomarkers applicable to adjuvant treatment of early‐stage CRC and focus on the future of this field.

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 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.

Optical phased arrays (OPAs), which manipulate an optical beam by controlling the phase of light, are optical devices characterized by high speed, small size, light weight, and high reliability that make various applications possible. In this study, an eight-channel-waveguide OPA using an electro-optic (EO) polymer for phase control was fabricated. Very high-speed optical beam scanning with a frequency of 2 MHz was demonstrated by applying a driving waveform superimposing sinusoidal and rectangular-wave voltages. Furthermore, the EO polymer OPA can be operated with a low total-operation power consumption of 0.38 mW at a scanning speed of 500 kHz.

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.

Aim To assess the impact of the Summit on Financial Markets and the World Economy held in Osaka City, Japan (G20 Osaka Summit) on the emergency medical services (EMS) system. Methods This study used the ORION database with its population‐based registry of emergency patients comprising both ambulance and in‐hospital records in Osaka Prefecture, Japan. The G20 Osaka Summit was held in Osaka City from 28 to 29 June, 2019. Changes in the EMS system and traffic regulations in Osaka were made during the period from 27 to 30 June, but we focused on the two summit days as the G20 period. The control periods comprised the same calendar days 1 week before and 1 week after the G20 period. We evaluated differences in the number of emergency transports, difficulties in obtaining hospital acceptance of patients, deaths among hospitalized emergency patients, and ambulance transport times between the two periods. Results In total, 2,590 cases in the G20 period and 5,152 cases in the control periods were registered. The relative risk of cases during the G20 versus control periods was 1.01 (0.96–1.05). Significant decreases were observed in the number of traffic accidents as ambulance calls (relative risk = 0.77; 95% confidence interval, 0.64–0.91). There were no significant differences in difficulties in obtaining hospital acceptance or deaths among hospitalized emergency patients between the G20 and control periods. In addition, ambulance transport times during the G20 period were not significantly longer than those in the control periods. Conclusion The G20 Osaka Summit did not adversely impact the provision of emergency medical care in the Osaka area.

Aim Surgical‐site infections (SSIs) often occur after surgery for colorectal perforation. We introduced delayed primary closure (DPC) after intrawound continuous negative pressure and irrigation treatment (IW‐CONPIT) to prevent SSIs. We aimed to evaluate the efficacy of DPC after IW‐CONPIT compared with primary closure (PC) after surgery for colorectal perforation. Methods We undertook a retrospective study including 22 patients who underwent DPC (DPC group) and 18 patients who underwent PC (PC group) at our hospital between April 2015 and January 2017. The primary outcome was the SSI rate. The secondary outcomes were other complications (