Effect of preoperative immunonutrition on fecal microbiota in colon cancer patients: a secondary analysis of a randomized controlled trial

BACKGROUND/OBJECTIVES@#This study aimed to evaluate the effect of preoperative immunonutrition on the composition of fecal microbiota following a colon cancer surgery.MATERIALS/METHODS: This study was a secondary analysis of a randomized controlled trial assessing the impact of preoperative immunonutrition on the postoperative outcomes of colon cancer surgery. Patients with primary colon cancer were enrolled and randomly assigned to receive additional preoperative immunonutrition or a normal diet alone.Oral nutritional supplementation (400 mL/day) with arginine and ω-3 fatty acids were administered to patients in the immunonutrition group for 7 days prior to surgery. Thirtytwo fecal samples were collected from 16 patients in each group, and the composition of fecal microbiota was compared between the 2 groups. @*RESULTS@#At the phylum level, no significant difference was observed in the composition of microbiota between the 2 groups (Firmicutes, 69.1% vs. 67.5%, P = 0.624; Bacteroidetes, 19.3% vs. 18.1%, P = 0.663; Actinobacteria, 6.7% vs. 10.6%, P = 0.080). The Firmicutes/Bacteroidetes ratio (4.43 ± 2.32 vs. 4.55 ± 2.51, P = 0.897) was also similar between the 2 groups. At the genus level, the proportions of beneficial bacteria such as Faecalibacterium spp. (8.1% vs. 6.4%, P = 0.328) and Prevotella spp. (6.9% vs. 4.8%, P = 0.331) were higher, while that of Clostridium spp. was lower (0.5% vs. 1.2%, P = 0.121) in the immunonutrition group, but the difference was not significant. @*CONCLUSIONS@#Immunonutrition showed no significant association with the composition of fecal microbiota. The relationship between immunonutrition and the fecal microbiota should be investigated further in large-scale studies.

Comparison of COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease shock syndrome: case reports and literature review

Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious complication of COVID-19 characterized by hyperinflammation and multi-organ dysfunction including shock. Shock is also seen in a severe form of Kawasaki disease (KD) called KD shock syndrome (KDSS). Here, we present one MIS-C and one KDSS case and compare similarities and differences between them. Both MIS-C (case 1) and KDSS (case 2) showed hyperinflammation, KD-related features, gastrointestinal problems, hypotension, and coagulopathy. The extent of systemic inflammation and organ dysfunction was more severe in KDSS than in MIS-C. Case 1 was diagnosed as MIS-C because SARS-CoV-2 was confirmed, and case 2 was diagnosed as KDSS because no pathogen was identified in microbiological studies. We believe that the most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger. Organ dysfunction is a hallmark of MIS-C and KDSS, but not KD, so MIS-C shares more clinical phenotypes with KDSS than with KD. Comparison of MIS-C and KDSS will be an interesting and important topic in the field of KD-like hyperinflammatory disease research.

Deep learning predicts the differentiation of kidney organoids derived from human induced pluripotent stem cells

Kidney organoids derived from human pluripotent stem cells (hPSCs) contain multilineage nephrogenic progenitor cells and can recapitulate the development of the kidney. Kidney organoids derived from hPSCs have the potential to be applied in regenerative medicine as well as renal disease modeling, drug screening, and nephrotoxicity testing. Despite biotechnological advances, individual differences in morphological and growth characteristics among kidney organoids need to be addressed before clinical and commercial application. In this study, we hypothesized that an automated noninvasive method based on deep learning of bright-field images of kidney organoids can predict their differentiation status. Methods: Bright-field images of kidney organoids were collected on day 18 after differentiation. To train convolutional neural networks (CNNs), we utilized a transfer learning approach. CNNs were trained to predict the differentiation of kidney organoids on bright-field images based on the messenger RNA expression of renal tubular epithelial cells as well as podocytes. Results: The best prediction model was DenseNet121 with a total Pearson correlation coefficient score of 0.783 on a test dataset. W classified the kidney organoids into two categories: organoids with above-average gene expression (Positive) and those with below-average gene expression (Negative). Comparing the best-performing CNN with human-based classifiers, the CNN algorithm had a receiver operating characteristic-area under the curve (AUC) score of 0.85, while the experts had an AUC score of 0.48. Conclusion: These results confirmed our original hypothesis and demonstrated that our artificial intelligence algorithm can successfully recognize the differentiation status of kidney organoids.

A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19

RationaleAlthough COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a muco-trapping monoclonal antibody would provide a more effective and convenient treatment for COVID-19. ObjectiveWe investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab, an approved intravenous treatment for COVID-19, for nebulized delivery by a handheld nebulizer. MethodsA Phase 1 study was conducted in healthy volunteers. Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetic measurements of IN-006 in nasal fluid and serum. ResultsTwenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and were graded mild to moderate in severity. Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 {micro}g/g of nasal fluid at 30 minutes after dosing and 5.8 {micro}g/g at 22 hours. Mean serum levels in the multiple dose cohort peaked at 0.55 {micro}g/mL at 3 days after the final dose. ConclusionsIN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above its inhibitory concentration. These data support further clinical development of IN-006. RegistrationAustralian New Zealand Clinical Trials Registry: ACTRN12621001235897

Stable nebulization and muco-trapping properties of Regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap SARS-CoV-2 virus-like-particles in fresh human airway mucus. IN-006, a reformulation of Regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Ischemic Vaso-occlusive Retinopathy as Initial Presentation in Pediatric Systemic Lupus Erythematosus: A Case Report

Ischemic vaso-occlusive retinopathy as an initial manifestation is rare in pediatric systemic lupus erythematosus (pSLE). A 13-year-old girl presented with two months’ history of papules and crusts with fatigue, weight loss, and abrupt hair loss. Pancytopenia and findings compatible with SLE, including positive direct Coombs’ test, antinuclear antibody (Ab), anti-double stranded DNA Ab, anti-Smith Ab, anti-ribonucleoprotein Ab, lupus anticoagulant, anti-β2 glycoprotein Immunoglobulin G, and anti-cardiolipin Ab, were detected. Bi-nasal hemianopsia was detected. Initial visual acuity was hand motion in the right eye and 15/20 in the left. Fundoscopy showed massive exudation around the optic disc with macular edema, vascular sheathing with perivascular hemorrhage in the whole retina, and ghost vessels in the peripheral retina. Intravitreal triamcinolone injection and dexamethasone implant injection were administered. Visual symptoms improved but did not recover. Methylprednisolone therapy and photocoagulation improved visual acuity and fever. Early intervention for retinopathy in pSLE can help prevent vision-loss.

Impact of circumferential tumor location of mid to low rectal cancer on oncologic outcomes after preoperative chemoradiotherapy

Purpose@#Some studies have suggested that circumferential tumor location (CTL) of rectal cancer may affect oncological outcomes. However, studies after preoperative chemoradiotherapy (CRT) are rare. This study aimed to evaluate the impact of CTL on oncologic outcomes of patients with mid to low rectal cancer who received preoperative CRT. @*Methods@#Patients with mid to low rectal cancer who underwent total mesorectal excision after CRT from January 2013 to December 2018 were included in this retrospective study. The impact of CTL on the pathological circumferential resection margin (CRM) status, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) was analyzed. @*Results@#Of the 381 patients, 98, 70, 127, and 86 patients were categorized into the anterior, posterior, lateral, and circumferential tumor groups, respectively. Tumor location was not significantly associated with the pathological CRM involvement (anterior, 12.2% vs. posterior, 14.3% vs. lateral, 11.0% vs. circumferential, 17.4%; P = 0.232). Univariate analyses revealed no correlation between CTL and 3-year LRFS (93.0% vs. 89.1% vs. 91.5% vs. 88%, P = 0.513), 3-year DFS (70.3% vs. 70.2% vs. 75.3% vs. 75.7%, P = 0.832), and 5-year OS (74.7% vs. 78.0% vs. 83.9% vs. 78.2%, P = 0.204). Multivariate analysis identified low rectal cancer and pathological CRM involvement as independent risk factors for all survival outcomes (all P < 0.05). @*Conclusion@#CTL of rectal cancer after preoperative CRT was not significantly associated with the pathological CRM status, recurrence, and survival.

The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants. HighlightsO_LICT-P59 exerts the antiviral effect on authentic Delta, Epsilon and Kappa variants in cell-based experiments. C_LIO_LICT-P59 showed neutralizing potency against variants including Delta, Epsilon, Kappa, L452R, T478K and P681H pseudovirus variants. C_LIO_LIThe administration of clinically relevant dose of CT-P59 showed in vivo C_LIO_LIprotection against Delta variants in animal challenge experiment. C_LI

Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2

P.1. or gamma variant also known as the Brazil variant, is one of the variants of concern (VOC) which appears to have high transmissibility and mortality. To explore the potency of the CT-P59 monoclonal antibody against P.1 variant, we tried to conduct binding affinity, in vitro neutralization, and in vivo animal tests. In in vitro assays revealed that CT-P59 is able to neutralize P.1 variant in spite of reduction in its binding affinity against a RBD (receptor binding domain) mutant protein including K417T/E484K/N501Y and neutralizing activity against P.1 pseudoviruses and live viruses. In contrast, in vivo hACE2 (human angiotensin-converting enzyme 2)-expressing TG (transgenic) mouse challenge experiment demonstrated that a clinically relevant or lower dosages of CT-P59 is capable of lowering viral loads in the respiratory tract and alleviates symptoms such as body weight losses and survival rates. Therefore, a clinical dosage of CT-P59 could compensate for reduced in vitro antiviral activity in P.1-infected mice, implying that CT-P59 has therapeutic potency for COVID-19 patients infected with P.1 variant. HighlightsO_LICT-P59 could bind to and neutralize P.1 variant, but CT-P59 showed reduced susceptibility in in vitro tests. C_LIO_LIThe clinical dosage of CT-P59 demonstrated in vivo therapeutic potency against P.1 variants in hACE2-expressing mice challenge study. C_LIO_LICT-P59 ameliorates their body weight loss and prevents the lethality in P.1 variant-infected mice. C_LI

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant. HighlightsO_LICT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virus C_LIO_LICT-P59 showed reduced potency against the B.1.351 variant in in vitro studies C_LIO_LITherapeutic dosage of CT-P59 showed in vivo neutralizing potency against B.1.351 in ferret challenge study. C_LI

Classification of endometriosis / 영남의대학술지

Endometriosis is a chronic disease associated with pelvic pain and infertility. Several classification systems for the severity of endometriosis have been proposed. Of these, the revised American Society for Reproductive Medicine classification is the most well-known. The ENZIAN classification was developed to classify deep infiltrating endometriosis and focused on the retroperitoneal structures. The endometriosis fertility index was developed to predict the fertility outcomes in patients who underwent surgery for endometriosis. Finally, the American Association of Gynecological Laparoscopists classification is currently being developed, for which 30 endometriosis experts are analyzing and researching data by assigning scores to categories considered important; however, it has not yet been fully validated and published. Currently, none of the classification systems are considered the gold standard. In this article, we review the classification systems, identify their pros and cons, and discuss what improvements need to be made to each system in the future.

The Relationship Between High-Output Stomas, Postoperative Ileus, and Readmission After Rectal Cancer Surgery With Diverting Ileostomy

Purpose@#This study aimed to evaluate the relationship between high-output stomas (HOSs), postoperative ileus (POI), and readmission after rectal cancer surgery with diverting ileostomy. @*Methods@#We included 302 patients with rectal cancer who underwent restorative resection with diverting ileostomy between January 2011 and December 2015. HOSs were defined as stomas with ≥ 2,000 mL/day output. We analyzed predictive factors for readmission of these patients. @*Results@#Forty-eight patients (15.9%) had HOSs during the hospital stay, and 41 patients (13.6%) experienced POI. HOSs were strongly associated with POI (45.8% vs. 7.5%, P < 0.001). The all-cause readmission rate was 16.9%, with 19 (6.3%) and 20 (6.6%) experiencing ileus and acute kidney injury, respectively. HOSs (27.1% vs. 15.0%, P = 0.040) and POI (34.1% vs. 14.2%, P = 0.002) were associated with all-cause readmission, and POI was associated with readmission with ileus (17.1% vs. 4.6%, P = 0.007). POI was an independent risk factor for all-cause readmission (adjusted odds ratio [OR], 2.640; 95% confidence interval [CI], 1.162 to 6.001; P = 0.020) and readmission with ileus (adjusted OR = 3.869; 95% CI 1.387 to 10.792; P = 0.010). @*Conclusion@#POI was associated with readmission, particularly for subsequent ileus, in patients with diverting ileostomy. We should make efforts to reduce POI, such as strong control of HOSs, to prevent readmission.

NaHCO 3- and NaCl-Type Hot Springs Enhance the Secretion of Inflammatory Cytokine Induced by Polyinosinic-Polycytidylic Acid in HaCaT Cells

Background@#Hot springs have been traditionally used as an alternative treatment for a wide range of diseases, including rheumatoid arthritis, bronchial asthma, diabetes, hypertension, psoriasis and atopic dermatitis. However, the clinical effects and therapeutic mechanisms associated with hot springs remain poorly defined. @*Objective@#The purpose of this study was to demonstrate the different effects of hot springs on cellular viability and secretion of inflammatory cytokines on keratinocyte in two geographically representative types of hot springs: NaHCO3 -type and NaCl-type, which are the most common types in South Korea. @*Methods@#We performed WST-1, BrdU measurements, human inflammatory cytokine arrays and enzyme-linked immunosorbent assay in HaCaT cells stimulated with toll-like receptor 3 by polyinosinic-polycytidylic acid. @*Results@#The interaction effects of cell viability and cell proliferation were not significantly different regardless of polyinosinic-polycytidylic acid stimulation and cultured hot springs type. Cytokine array and enzyme-linked immunosorbent assay analysis showed increased expression of inflammatory cytokines such as interleukin-6 and granulocyte-macrophage colony-stimulating factor by polyinosinic-polycytidylic acid stimulation, with expression levels differing according to hot springs hydrochemical composition. Cytokine reduction was not significant. @*Conclusion@#The effects and mechanisms of hot springs treatment in keratinocytes were partially elucidated.

NaHCO 3- and NaCl-Type Hot Springs Enhance the Secretion of Inflammatory Cytokine Induced by Polyinosinic-Polycytidylic Acid in HaCaT Cells

Background@#Hot springs have been traditionally used as an alternative treatment for a wide range of diseases, including rheumatoid arthritis, bronchial asthma, diabetes, hypertension, psoriasis and atopic dermatitis. However, the clinical effects and therapeutic mechanisms associated with hot springs remain poorly defined. @*Objective@#The purpose of this study was to demonstrate the different effects of hot springs on cellular viability and secretion of inflammatory cytokines on keratinocyte in two geographically representative types of hot springs: NaHCO3 -type and NaCl-type, which are the most common types in South Korea. @*Methods@#We performed WST-1, BrdU measurements, human inflammatory cytokine arrays and enzyme-linked immunosorbent assay in HaCaT cells stimulated with toll-like receptor 3 by polyinosinic-polycytidylic acid. @*Results@#The interaction effects of cell viability and cell proliferation were not significantly different regardless of polyinosinic-polycytidylic acid stimulation and cultured hot springs type. Cytokine array and enzyme-linked immunosorbent assay analysis showed increased expression of inflammatory cytokines such as interleukin-6 and granulocyte-macrophage colony-stimulating factor by polyinosinic-polycytidylic acid stimulation, with expression levels differing according to hot springs hydrochemical composition. Cytokine reduction was not significant. @*Conclusion@#The effects and mechanisms of hot springs treatment in keratinocytes were partially elucidated.

Benzydamine inhibits osteoclast differentiation and bone resorption down-regulation of interleukin-1 expression

Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1 (IL-1) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1 treatment. The reporter assay and the inhibitor study of IL-1 transcription suggested that BA inhibited nuclear factor-B and activator protein-1 by regulating IB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1 expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.

Is radical surgery for clinical stage I right-sided colon cancer relevant? A retrospective review

PURPOSE: Radical lymph node dissection for right-sided colon cancer is technically challenging. No clear guideline is available for surgical resection of clinical stage I right-sided colon cancer. This study was designed to review the pathologic stage of clinical stage I right-sided colon cancer and determine the relevant extent of surgical resection.METHODS: Patients were treated for clinical stage I right-sided colon cancers (cecal, ascending, hepatic flexure, and proximal transverse colon) between July 2006 and December 2014 at a tertiary teaching hospital. Open surgery was not included because laparoscopic surgery is an initial major procedure in the institution.RESULTS: During the study period, 80 patients diagnosed with clinical stage I right-sided colon cancer were classified into 2 groups according to the pathology: stage 0/I and II/III. Tumor sizes were larger in the stage II/III group (P = 0.003). The stage II/III group had higher rates of vascular (P = 0.023) and lymphatic invasion (P = 0.023) and lower rates of well differentiation (P = 0.022). During follow-up, 1 case of local and 4 cases of systemic recurrences were found. Multivariate analysis to confirm odds ratios affecting change from clinical stage I to pathological stage II/III showed that tumor size (P = 0.010) and the number of retrieved lymph nodes (P = 0.046) were risk factors.CONCLUSION: For right-sided colon cancer, even with clinical stage I included, radical lymph node dissection should be performed for exact staging with sufficient number of lymph nodes. This will help determine appropriate adjuvant treatment, especially in large tumor sizes.

Clinical and histopathologic analysis of gynecological cancer: a single institute experience over 7 years / 영남의대학술지

Background@#Approximately 100,000 women are diagnosed with cancer each year in Korea. According to a survey by the Korean central cancer registry in 2016, uterine cervical cancer, uterine corpus cancer, and ovarian cancer were the 5th, 7th, and 8th most prevalent cancers respectively among Korean women. The present study aims to review the clinico-pathologic characteristics of patients who were treated for major gynecological malignancies at Yeungnam University Medical Center. @*Methods@#Patients with invasive gynecological cancers from January 2012 to February 2019 were retrospectively identified. We analyzed the clinical features, demographic profiles, pathologic data, treatment modality used, adjuvant treatment used, complications, recurrence, and survival outcomes. @*Results@#A total of 287 patients (cervical cancer 115; corporal cancer 86; and ovarian, tubal, or primary peritoneal cancer 90) were included. Most cervical (82.7%) and corporal cancers (89.5%) were diagnosed in the early stages (stage I or II), while more than half (58.9%) the cases of ovarian, tubal or peritoneal cancers were diagnosed in the advanced stages (stage III or IV). Surgical complications were observed in 12.2% of cervical cancers, 16.3% of uterine corpus cancers, and 11.1% of ovarian, tubal, and peritoneal cancers, respectively. The 5-year overall survival rate was 94.1%, 91.0%, and 77.1% for cervical, corporal, and ovarian, tubal, or peritoneal cancers, respectively. @*Conclusion@#Surgical treatment was satisfactory in terms of the incidence of complications, and survival outcomes were generally good. Clinicians should be aware of the clinical and histopathological characteristics of patients with gynecological cancers to be able to provide optimal strategies and counseling.

Double Primary Mucinous Eccrine Adenocarcinomas Each Occurring Separately on the Left Eyelid and Right Eyelid with a Time Lag / 대한피부과학회지

A 57-year-old man presented with a tender, solitary, 0.3 cm-sized, subdermal nodule on the left periocular area for several months. He had surgery three times for recurrent primary mucinous eccrine adenocarcinoma on the right periocular area. Skin biopsy showed a tumor separated by strands of fibrous tissue and small compartments of tumor cells were surrounded by pale-staining mucin. The cluster of tumor cells contained atypical epithelial cells. The mucin stained with periodic acid-Schiff (PAS) and alcian blue at pH 2.5. Cytokeratin-7 (CK7) was positive for tumor cells, but cytokeratin-20 (CK20) and S-100 were negative. For evaluation of local metastasis, computed tomography was performed and there was no evidence of regional lymph node metastasis. The lesion was removed by local excision and the patient was under close follow up without any sign of recurrence. To our knowledge, double primary mucinous eccrine adenocarcinomas in the opposite body site has never been reported.

Tailored treatment of anastomotic leak after rectal cancer surgery according to the presence of a diverting stoma

Purpose@#A variety of clinical features of anastomotic leak occur during the surgical treatment of rectal cancer. However, little information regarding management of leakage is available and treatment guidelines have not been validated. The aim of this study was to evaluate the validity of currently proposed expert opinions on the management of anastomotic leak, after low anterior resection for rectal cancer. @*Methods@#A retrospective analysis was conducted for 1,786 patients who underwent sphincter-preserving surgery for rectal cancer between 2005 and 2015. Clinical outcomes including anastomotic leak-associated mortality and permanent stoma were analyzed. @*Results@#The overall incidence of anastomotic leak was 6.8% (122 of 1,786), including 6.1% (30 of 493 patients) with diverting stoma and 7.1% (92 of 1,293 patients) without diverting stoma (p = 0.505). A majority of patients without diversion were treated with diverting stoma (76 of 88 patients [86.4%]); 1 mortality (0.8%) was observed in this group. Treatments in the diversion group mainly included conservative treatment, local drainage, and/or transanal repair (26 of 30 patients [86.7%]).The anastomotic failure rates were 20.7% (19 of 92 patients) in the no diversion group and 53.3% (16 of 30 patients) in the diversion group. In the multivariate analysis, preoperative chemoradiotherapy (p < 0.001) and delayed diagnosis of anastomotic leak (p = 0.036) were independent risk factors for permanent stoma. @*Conclusion@#Management of anastomotic leak should be tailored to individual patients. When anastomotic leak occurred, preoperative chemoradiotherapy and delayed diagnosis seemed to be associated with permanent stoma.

Effects of tranexamic acid on the activity of glutamate transporter EAAT3

Background@#Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type. @*Methods@#EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 M L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (C). Results were presented as mean  SEM. @*Results@#TXA (30 to 1,000 M) significantly decreased EAAT3 activity. Our kinetic study showed that Vmax was significantly decreased in the TXA group compared with the control group (1.1  0.1 vs. 1.4  0.1 C, n = 18–23, P = 0.043), but the Km did not significantly change (12.7  3.9 M for TXA vs. 12.8  3.8 for control, n = 18–23, P = 0.986). @*Conclusions@#Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect.