Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules.

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), transfer bioactive molecules from donor to recipient cells in various pathophysiological settings, thereby mediating intercellular communication. Despite their significant roles in extracellular signaling, the cellular uptake mechanisms of different EV subpopulations remain unknown. In particular, plasma membrane-derived MVs are larger vesicles (100 nm to 1 µm in diameter) and may serve as efficient molecular delivery systems due to their large capacity; however, because of size limitations, receptor-mediated endocytosis is considered an inefficient means for cellular MV uptake. This study demonstrated that macropinocytosis (lamellipodia formation and plasma membrane ruffling, causing the engulfment of large fluid volumes outside cells) can enhance cellular MV uptake. We developed experimental techniques to induce macropinocytosis-mediated MV uptake by modifying MV membranes with arginine-rich cell-penetrating peptides for the intracellular delivery of therapeutic molecules.

[A Recurrent Colon Cancer Successfully Treated by Nivolumab plus Ipilimumab with On and Off for Preventing Exacerbation of Skin Disorders].

Here, we report a case in which nivolumab plus ipilimumab combination therapy was significantly effective for MSI-high recurrent colon cancer with acute exacerbation after 5-FU/L-OHP/CPT-11 treatment. At the end of 4 cycles of combination therapy, clinical CR was obtained on diagnostic imaging. At the end of the 2 cycles of transition from combination therapy to monotherapy, eosinophilia was observed in a quadratic function, and exacerbation of skin disorders was observed. Eosinophil counts normalized promptly after discontinuation of treatment, and skin disorders gradually improved. Two months after the discontinuation of treatment, monotherapy was restarted. After the resumption of treatment, an increase in eosinophils and worsening of skin symptoms were observed again, and stopped treatment. We report an interesting case in which immune checkpoint inhibiter were turned on and off according to eosinophil counts for preventing exacerbation of skin disorders, and for maintaining cancer remission by continuing immune checkpoint inhibitor treatment.

Plasmacytoid dendritic cells stimulated with Lactococcus lactis strain Plasma produce soluble factors to suppress SARS-CoV-2 replication.

Innate immune responses are important in the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. We have previously found a lactic acid bacteria species, Lactococcus lactis strain Plasma (LC-Plasma), which possesses specific feature to activate plasmacytoid dendritic cells (pDCs) and thus may affect innate immune responses. Here, we investigated the impact of pDC activation by LC-Plasma on SARS-CoV-2 replication in vitro. Addition of the culture supernatant of pDCs stimulated with LC-Plasma resulted in suppression of SARS-CoV-2 replication in Vero and Calu-3 cells. We confirmed interferon-α (IFN-α) secretion in the supernatant of pDCs stimulated with LC-Plasma and induction of IFN-stimulated genes in cells treated with the pDC supernatant. Anti-IFN-α antibody impaired the suppression of SARS-CoV-2 replication by the supernatant of LC-Plasma-stimulated pDCs, suggesting that IFN-α plays an important role in the SARS-CoV-2 suppression. Our results indicate the potential of LC-Plasma to induce inhibitory responses against SARS-CoV-2 replication through pDC stimulation with IFN-α secretion.

Efficacy of Lactococcus lactis strain plasma (LC-Plasma) in easing symptoms in patients with mild COVID-19: protocol for an exploratory, multicentre, double-blinded, randomised controlled trial (PLATEAU study).

INTRODUCTION: The COVID-19 pandemic has been a major concern worldwide; however, easily accessible treatment options for patients with mild COVID-19 remain limited. Since the oral intake of Lactococcus lactis strain plasma (LC-Plasma) enhances both the innate and acquired immune systems through the activation of plasmacytoid dendritic cells (pDCs), we hypothesised that the oral intake of LC-Plasma could aid the relief or prevention of symptoms in patients with asymptomatic or mild COVID-19. METHODS AND ANALYSIS: This is an exploratory, multicentre, double-blinded, randomised, placebo-controlled trial. This study was initiated in December 2021 and concludes in April 2023. The planned number of enrolled subjects is 100 (50 subjects×2 groups); subject enrolment will be conducted until October 2022. Patients with asymptomatic or mild COVID-19 will be enrolled and randomly assigned in a 1:1 ratio to group A (oral intake of LC-Plasma-containing capsule, 200 mg/day, for 14 days) or group B (oral intake of placebo capsule, for 14 days). The primary endpoint is the change in subjective symptoms measured by the severity score. Secondary endpoints include SARS-CoV-2 viral loads, biomarkers for pDC activation, serum SARS-CoV-2-specific antibodies, serum cytokines, interferon and interferon-inducible antiviral effectors and the proportion of subjects with emergency room visits to medical institutions or who are hospitalised. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Review Board of Nagasaki University, in accordance with the Clinical Trials Act of Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported in journal publications. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (registration number: jRCTs071210097).

Fecal Microbes Associated with the Outcomes After Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: Although accumulating evidence suggests that an imbalanced gut microbiota leads to cancer progression, few studies demonstrated the implication in patients who underwent oncologic esophagectomy. This study aimed to elucidate the association between gut microbes and the outcomes after oncologic esophagectomy, as well as the host's inflammatory/nutritional status. METHODS: Overall, 783 consecutive patients who underwent oncologic esophagectomy were eligible. We investigated the microbiota detected by fecal culture tests and then assessed the association between the gut microbiota and patient characteristics, short-term outcomes, and long-term survival. RESULTS: Seventeen different species could be cultivated. We comprehensively examined the impact of each detected microbe on survival. The presence of Bacillus species (Bacillus sp.; 26.8%) was associated with favorable prognosis on overall and cancer-specific survival (p = 0.02 and 0.02, respectively). Conversely, the presence of Proteus mirabilis (P. mirabilis; 3.4%) was associated with unfavorable overall and recurrence-free survivals (p = 0.02 and < 0.01, respectively). Multivariate analysis showed that the presence of P. mirabilis was one of the independent prognostic factors for poor recurrence-free survival (p < 0.01). Patients with Bacillus sp. had lower modified Glasgow prognostic score and better response to preoperative treatment than those without (p = 0.01 and 0.03, respectively). Meanwhile, patients with P. mirabilis were significantly associated with higher systemic inflammation scores and increased postoperative pneumonia incidence than those without (p = 0.01 and 0.02, respectively). CONCLUSIONS: Preoperative fecal microbiota was associated with the host's inflammatory and nutritional status and may influence the outcomes after oncologic esophagectomy.

Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog.

Blocking the interaction between CD28 and B7 by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a potent immune checkpoint that prevents damage to host tissues from excessive immune responses. However, it also significantly diminishes immune responses against cancers and allows cancer cell growth. This study found that recombinant (r) human (h) CTLA-4 specifically binds to canine dendritic cells (DCs) and suppresses the responses of canine T cells to allogeneic DCs. ERY2-4, a peptide targeting rhCTLA-4 selected from a yeast-displayed library of helix-loop-helix (HLH) peptides and improved to have a binding affinity to rhCTLA-4 as strong as that of rhB7, inhibited the binding of rhCTLA-4 to canine DCs. Furthermore, the targeting peptide significantly enhanced the response of canine T cells to allogeneic DCs. These results suggest that the CTLA-4-targeting peptide enhances canine T cell activity by blocking the interaction between canine CTLA-4 on T cells and canine B7 on DCs. This study demonstrates the generation of a new type of immune checkpoint inhibitor, which may be applicable to cancer therapy in dogs.

Is Prophylactic Cervical Drainage Effective in Patients Undergoing McKeown Esophagectomy Reconstructed Through the Retrosternal Route with Two-Field Lymphadenectomy?

BACKGROUND: McKeown esophagectomy with two-field lymphadenectomy is the treatment of choice for oncologic esophagectomy. A cervical drain is placed in cases after modern two-field lymph node dissection (M2FD) to provide information on anastomotic leakage. However, the necessity of prophylactic cervical drainage during surgery remains unknown. This study aimed to clarify the clinical significance of cervical drainage in patients who underwent McKeown esophagectomy with M2FD. METHODS: A total of 293 patients underwent McKeown surgery with two-field lymphadenectomy at our institute between January 2013 and December 2019. We compared the day of drain removal, amount of drainage volume, and the appearance of drainage fluid between patients with and without anastomotic leakage. RESULTS: McKeown esophagectomy reconstructed through the retrosternal route is 203 patients (69.3%) of all. Nineteen patients (6.5%) experienced anastomotic leakage. The amount of cervical drain discharge was comparable between patients with and without anastomotic leakage. In addition, no purulent or salivary discharge was observed in patients with anastomotic leakage. There was no difference in the median day of drain removal between the groups. The initial clinical findings for the diagnosis of anastomotic leakage were surgical site infection in 10 (52.6%), fever in 5 (26.3%), prolonged inflammation in a blood test in 3 (15.8%), and bloody discharge from the chest tube in 1 (5.3%). There was no mortality due to any cause. CONCLUSION: A prophylactic cervical drain may not be mandatory in patients with esophageal cancer undergoing McKeown esophagectomy reconstructed through the retrosternal route with two-field lymphadenectomy.

C-reactive protein to prealbumin ratio: a useful inflammatory and nutritional index for predicting prognosis after curative resection in esophageal squamous cell carcinoma patients.

PURPOSE: Although C-reactive protein to prealbumin ratio (CPR) can predict the outcomes of several types of cancer surgeries, little is known about the implication of CPR in patients undergoing esophagectomy for esophageal squamous cell carcinoma (ESCC). METHODS: Between 2009 and 2018, 682 consecutive ESCC patients who underwent curative esophagectomy were enrolled. The clinicopathological factors and prognoses were compared between the groups stratified by preoperative CPR levels. A logistic regression model was used to determine the risk factors of postoperative pneumonia. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to elucidate prognostic factors. RESULTS: There were more elderly patients, more males, and more advanced clinical T and N categories in the high CPR group than in the low CPR group. Also, the incidence of postoperative pneumonia was significantly higher in the high CPR group than in the low CPR group (32.4% vs. 20.3%, p < 0.01). In multivariate analyses, high CPR was one of the independent predictive factors for postoperative pneumonia (OR, 1.71; 95% CI, 1.15-2.54; p < 0.03). Moreover, high CPR was an independent prognostic factor for overall, cancer-specific, and recurrence-free survivals (HR 1.62; 95% CI 1.18-2.23; p < 0.01, HR 1.57; 95% CI 1.08-2.32; p = 0.02, HR 1.42; 95% CI 1.06-1.90; p = 0.02). CONCLUSION: Preoperative CPR was found to be a useful inflammatory and nutritional indicator for predicting the occurrence of pneumonia and prognosis in patients with ESCC undergoing esophagectomy.

Long-Term Insufficiency of Oral Intake after Esophagectomy: Who Needs Intense Nutritional Support after Esophagectomy?

BACKGROUND: Patients with esophageal cancer are at a high risk of malnutrition after esophagectomy, and nutritional support may at times be required for several months following surgery. In this study, we aimed to clarify the clinical features and preoperative risk factors of patients with long-term insufficiency of oral intake after esophagectomy by evaluating the duration of feeding enterostomy placement. METHODS: A total of 306 patients who underwent esophagectomy, reconstruction with gastric conduit, and feeding enterostomy creation were retrospectively reviewed. We analyzed the clinical features and preoperative risk factors for long-term placement of feeding enterostomy. RESULTS: The feeding enterostomy tube was removed less than 90 days after esophagectomy in 234 patients (76.5%) (short group), whereas 72 patients still needed enteral nutrition after 90 days (23.5%; long group). Although severe malnutrition was observed more frequently in the long group compared with the short group (p = 0.021), overall survival time was comparable between the groups (p = 0.239). Multivariate analysis revealed that higher age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.07; p = 0.021), poor performance status (OR 2.94; 95% CI, 1.10-7.87; p = 0.032), and lower preoperative body weight (BW) (OR 0.96; 95% CI, 0.94-0.99; p = 0.009) were the independent variables predicting the long-time placement of feeding enterostomy. CONCLUSION: Nutritional support via feeding enterostomy for more than 90 days after esophagectomy was required in 23.5% of patients. The elderly, poor performance status, and lower BW were the independent preoperative factors for predicting the long-term placement of feeding enterostomy.

Outcomes of esophagectomy for patients with esophageal squamous cell carcinoma accompanied by recurrent laryngeal nerve palsy at diagnosis.

BACKGROUND: Hoarseness is one of the classical symptoms in patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC), and it results from recurrent laryngeal nerve palsy, which is caused by nodal metastasis along the recurrent laryngeal nerve or by main tumors. We reviewed the short-term and long-term results of esophagectomy for patients with locally advanced ESCC and hoarseness at diagnosis. PATIENTS: Patients who initially presented with hoarseness from recurrent laryngeal nerve palsy between 2009 and 2018 and underwent esophagectomy for thoracic ESCC were eligible for this study. Pharyngolaryngectomy or cervical ESCC were exclusionary. RESULTS: A total of 15 patients were eligible, and 14 underwent resection of the recurrent laryngeal nerves. The remaining patient had nerve-sparing surgery. Nine patients (60%) had post-operative complications ≥ Clavien-Dindo class II and, pulmonary complications were most common. Two patients (13%) died in the hospital. The 5-year overall survival rate for all patients was 16%. Age (≤ 65 years), cT1/T2 tumor, and remarkably good response to neoadjuvant treatment were likely related to longer survival; however, these relationships were not statistically significant. CONCLUSIONS: Esophagectomy for ESCC patients who are diagnosed with recurrent laryngeal nerve paralysis at initial presentation could be a treatment option if the patient is relatively young, has a cT1/T2 tumor, or shows a remarkably good response to neoadjuvant treatment. However, clinicians should be aware of the possibility of postoperative pulmonary complications, which were frequently observed with the procedure.

Current status of robot-assisted minimally invasive esophagectomy: what is the real benefit?

Robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer has been performed increasingly frequently over the last few years. Robotic systems with articulated devices and tremor filtration allow surgeons to perform such procedures more meticulously than by hand. The feasibility of RAMIE has been demonstrated in several retrospective comparative studies, which showed similar short-term outcomes to conventional minimally invasive esophagectomy (cMIE). Considering the number of harvested lymph nodes, RAMIE may be superior to cMIE in terms of left upper mediastinal lymph node dissection. However, whether or not the addition of a robotic system to cMIE can help improve perioperative and oncological outcomes remains unclear. Given the lack of established evidence from randomized controlled trials, we must await the results of ongoing studies to reach any meaningful conclusions. Further advancements in robotic platforms, as well as the reduction in medical expenses, will be essential to demonstrate the real benefit of RAMIE.

Structure of mitogen-activated protein kinase kinase 1 in the DFG-out conformation.

Eukaryotic protein kinases contain an Asp-Phe-Gly (DFG) motif, the conformation of which is involved in controlling the catalytic activity, at the N-terminus of the activation segment. The motif can be switched between active-state (DFG-in) and inactive-state (DFG-out) conformations: however, the mechanism of conformational change is poorly understood, partly because there are few reports of the DFG-out conformation. Here, a novel crystal structure of nonphosphorylated human mitogen-activated protein kinase kinase 1 (MEK1; amino acids 38-381) complexed with ATP-γS is reported in which MEK1 adopts the DFG-out conformation. The crystal structure revealed that the structural elements (the αC helix and HRD motif) surrounding the active site are involved in the formation/stabilization of the DFG-out conformation. The ATP-γS molecule was bound to the canonical ATP-binding site in a different binding mode that has never been found in previously determined crystal structures of MEK1. This novel ATP-γS binding mode provides a starting point for the design of high-affinity inhibitors of nonphosphorylated inactive MEK1 that adopts the DFG-out conformation.

Chemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries.

Conformationally constrained peptides hold promise as molecular tools in chemical biology and as a new modality in drug discovery. The construction and screening of a target-focused library could be a promising approach for the generation of de novo ligands or inhibitors against target proteins. Here, we have prepared a protein kinase-focused library by chemically modifying helix-loop-helix (HLH) peptides displayed on phage and subsequently tethered to adenosine. The library was screened against aurora kinase A (AurA). The selected HLH peptide Bip-3 retained the α-helical structure and bound to AurA with a KD value of 13.7 µM. Bip-3 and the adenosine-tethered peptide Bip-3-Adc provided IC50 values of 103 µM and 7.7 µM, respectively, suggesting that Bip-3-Adc bivalently inhibited AurA. In addition, the selectivity of Bip-3-Adc to several protein kinases was tested, and was highest against AurA. These results demonstrate that chemical modification can enable the construction of a kinase-focused library of phage-displayed HLH peptides.

Mutation Analysis of the rpoB Gene in the Radiation-Resistant Bacterium Deinococcus radiodurans R1 Exposed to Space during the Tanpopo Experiment at the International Space Station.

To investigate microbial viability and DNA damage, dried cell pellets of the radiation-resistant bacterium Deinococcus radiodurans were exposed to various space environmental conditions at the Exposure Facility of the International Space Station (ISS) as part of the Tanpopo mission. Mutation analysis was done by sequencing the rpoB gene encoding RNA polymerase ß-subunit of the rifampicin-resistant mutants. Samples included bacteria exposed to the space environment with and without exposure to UV radiation as well as control samples held in the ISS cabin and at ground. The mutation sites of the rpoB gene obtained from the space-exposed and ISS/ground control samples were similar to the rpoB mutation sites previously reported in D. radiodurans. Most mutations were found at or near the rifampicin binding site in the RNA polymerase ß-subunit. Mutation sites found in UV-exposed samples were mostly shared with non-exposed and ISS/ground control samples. These results suggest that most mutations found in our experiments were induced during procedures that were applied across all treatments: preparation, transfer from our laboratory to the ISS, return from the ISS, and storage before analysis. Some mutations may be enhanced by specific factors in the space experiments, but the mutations were also found in the spontaneous and control samples. Our experiment suggests that the dried cells of the microorganism D. radiodurans can travel without space-specific deterioration that may induce excess mutations relative to travel at Earth's surface. However, upon arrival at a recipient location, they must still be able to survive and repair the general damage induced during travel.

Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery.

The antimicrobial protein CAP18 (approximate molecular weight: 18 000), which was first isolated from rabbit granulocytes, comprises a C-terminal fragment that has negatively charged lipopolysaccharide binding activity. In this study, we found that CAP18 (106-121)-derived (sC18)2 peptides have macropinocytosis-inducible biological functions. In addition, we found that these peptides are highly applicable for use as extracellular vesicle (exosomes, EV)-based intracellular delivery, which is expected to be a next-generation drug delivery carrier. Here, we demonstrate that dimerized (sC18)2 peptides can be easily introduced on EV membranes when modified with a hydrophobic moiety, and that they show high potential for enhanced cellular uptake of EVs. By glycosaminoglycan-dependent induction of macropinocytosis, cellular EV uptake in targeted cells was strongly increased by the peptide modification made to EVs, and intriguingly, our herein presented technique is efficiently applicable for the cytosolic delivery of the biologically cell-killing functional toxin protein, saporin, which was artificially encapsulated in the EVs by electroporation, suggesting a useful technique for EV-based intracellular delivery of biofunctional molecules.

Additional Treatment Following Noncurative Endoscopic Resection for Esophageal Squamous Cell Carcinoma: A Comparison of Outcomes between Esophagectomy and Chemoradiotherapy.

BACKGROUND: Endoscopic resection (ER) has been widely implemented for cT1N0 esophageal squamous cell carcinoma (ESCC). Additional therapy, including esophagectomy and chemoradiotherapy (CRT), is sometimes required after noncurative ER. METHODS: We retrospectively reviewed 108 patients who received any additional treatment following noncurative ER (positive vertical margins, lymphovascular invasion, or invasion depth of submucosa or more), and compared the short- and long-term outcomes between the two treatment modalities. RESULTS: Of 108 patients, 56 underwent esophagectomy (E group), and 52 received CRT (CRT group). A positive vertical margin was observed in 17 (14.8%) patients and high risks of occult lymph node metastasis were observed in 91 (85.2%) patients, as well as lymphovascular invasion in 35 (32.4%) patients, invasion depth of the submucosa or more in 27 (25.0%) patients, and both in 29 (26.9%) patients. The E group patients were significantly younger (p = 0.046) and tended to present with larger tumors than those in the CRT group (p = 0.057). Lymphatic invasion was more frequent in the E group (p = 0.019), and, furthermore, one treatment-related death was observed in the E group. There were no significant differences between the groups in overall and disease-specific survival (p = 0.406 and 0.151, respectively), however, recurrence was only observed in the CRT group. CONCLUSION: Both esophagectomy and CRT are safe and effective as additional treatments after noncurative ER in patients with ESCC. Esophagectomy is oncologically safe, whereas a risk of postoperative morbidity and mortality remains. Although the adverse events are acceptable, CRT has a certain degree of risk of disease recurrence.

A web-based survey on various symptoms of computer vision syndrome and the genetic understanding based on a multi-trait genome-wide association study.

A variety of eye-related symptoms due to the overuse of digital devices is collectively referred to as computer vision syndrome (CVS). In this study, a web-based survey about mind and body functions, including eye strain, was conducted on 1998 Japanese volunteers. To investigate the biological mechanisms behind CVS, a multi-trait genome-wide association study (GWAS), a multivariate analysis on individual-level multivariate data, was performed based on the structural equation modeling methodology assuming a causal pathway for a genetic variant to influence each symptom via a single common latent variable. Twelve loci containing lead variants with a suggestive level of significance were identified. Two loci showed relatively strong signals and were associated with TRABD2B relative to the Wnt signaling pathway and SDK1 having neuronal adhesion and immune functions, respectively. By utilizing publicly available eQTL data, colocalization between GWAS and eQTL signals for four loci was detected, and a locus on 2p25.3 showed a strong colocalization (PPH4 > 0.9) on retinal MYT1L, known to play an important role in neuronal differentiation. This study suggested that the use of multivariate questionnaire data and multi-trait GWAS can lead to biologically reasonable findings and enhance our genetic understanding of complex relationships among symptoms related to CVS.

Airflow Limitation Predicts Postoperative Pneumonia after Esophagectomy.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is known to be a risk factor of pneumonia after esophagectomy. In this study, we investigated the relationship of airflow limitation with the occurrence and the severity of pneumonia in esophageal cancer patients who underwent esophagectomy. METHODS: We enrolled 844 patients who underwent curative esophagectomy between 2009 and 2018. The airflow limitation was evaluated using the percent-predicted forced expiratory volume at 1 s (%FEV1) with spirometry. RESULTS: There were 597 (70.7%), 141 (16.7%), 68 (8.1%), and 38 patients (4.5%) with %FEV1 of ≥ 90%, 80-90%, 70-80%, and < 70% categories, respectively. One hundred and ninety-one patients (22.6%) occurred pneumonia, and the incidences of pneumonia in each category of patients were 18.8%, 28.4%, 29.4%, and 50.0%, respectively. In multivariate analysis, the categories of 80%-90%, 70-80%, and < 70% were significantly associated with a higher incidence of postoperative pneumonia (OR 1.57; 95% CI 1.02-2.43, OR 1.87; 95% CI 1.04-3.36, OR 3.34; 95% CI 1.66-6.71, respectively), with the %FEV1 category of ≥ 90% as reference. The incidence of severe pneumonia of Clavien-Dindo grade III or higher was also significantly associated with the %FEV1. In patients without COPD, the incidence of pneumonia was significantly higher in those with %FEV1 < 90% than in those with %FEV1 ≥ 90% (32.2% versus 17.5%, p < 0.001). CONCLUSIONS: The airflow limitation can help predict the occurrence of pneumonia after esophagectomy in patients with and without COPD. Exclusive preventive measures should be considered in patients with reduced %FEV1 undergoing esophagectomy.

Influence of Damaged Stomach on Anastomotic Leakage following Cervical Esophagogastrostomy in Patients with Esophageal Cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the most common complications after esophagectomy. Although some patients have a history of peptic ulcers or other prior stomach diseases, the influence of a damaged stomach (DS) on AL incidence remains unclear. Therefore, we investigated the association between DS and incidence of AL in patients who underwent esophagectomy. PATIENTS AND METHODS: Between 2015 and 2019, a total of 447 consecutive patients who underwent cervical esophagogastrostomy using gastric tube following esophagectomy were enrolled. DS was defined on the basis of endoscopic findings of ulcers or scars due to medical history or prior treatment. We compared the incidence of AL between patients with DS and those with a healthy stomach (HS). Univariate and multivariate logistic regression analyses were used to identify factors that could predict AL incidence. RESULTS: Fifty-one patients (11.4%) had DS. Causes of DS included peptic ulcer (n = 36), endoscopic resection for early gastric cancer (n = 9), percutaneous endoscopic gastrostomies (n = 5), and post-chemotherapy scar for gastric malignant lymphoma (n = 1). Overall, AL occurred in 35 patients (7.8%). The incidence of AL in the DS group was significantly higher than in the HS group (15.7 vs. 6.8%, p = 0.03). DS was one of the independent predictive factors for AL (odds ratio, 2.75; 95% confidence interval, 1.10-6.92; p = 0.03) on multivariate analysis. Further, the diseases in the lower third of the conduit were associated with AL. CONCLUSIONS: Presence of DS can predict AL in patients who underwent cervical esophagogastrostomy after esophagectomy.