Residual embryonic cells as precursors of a Barrett's-like metaplasia.

Barrett's esophagus is an intestine-like metaplasia and precursor of esophageal adenocarcinoma. Triggered by gastroesophageal reflux disease, the origin of this metaplasia remains unknown. p63-deficient mice, which lack squamous epithelia, may model acid-reflux damage. We show here that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett's metaplasia. We track its source to a unique embryonic epithelium that is normally undermined and replaced by p63-expressing cells. Significantly, we show that a discrete population of these embryonic cells persists in adult mice and humans at the squamocolumnar junction, the source of Barrett's metaplasia. We show that upon programmed damage to the squamous epithelium, these embryonic cells migrate toward adjacent, specialized squamous cells in a process that may recapitulate early Barrett's. Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity.

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection.

The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease.

Metastatic potentials classified with hypoxia-inducible factor 1 downstream genes in pan-cancer cell lines.

Hypoxia-inducible factor 1 (HIF1) is a transcription factor that is stabilized under hypoxia conditions via post-translational modifications. HIF1 regulates tumor malignancy and metastasis by gene transcriptions, such as Warburg effect and angiogenesis-related genes, in cancer cells. However, the HIF1 downstream genes show varied expressional patterns in different cancer types. Herein, we performed the hierarchical clustering based on the HIF1 downstream gene expression patterns using 1406 cancer cell lines crossing 30 types of cancer to understand the relationship between HIF1 downstream genes and the metastatic potential of cancer cell lines. Two types of cancers, including bone and breast cancers, were classified based on HIF1 downstream genes with significantly altered metastatic potentials. Furthermore, different HIF1 downstream gene subsets were extracted to discriminate each subtype for these cancer types. HIF1 downstream subtyping classification will help to understand the novel insight into tumor malignancy and metastasis in each cancer type.

Analysis of the responsiveness to antiandrogens in multiple breast cancer cell lines.

Antiandrogens were originally developed as therapeutic agents for prostate cancer but are also expected to be effective for breast cancer. However, the role of androgen signaling in breast cancer has long been controversial due to the limited number of experimental models. Our study aimed to comprehensively investigate the efficacy of antiandrogens on breast cancer. In the present study, a total of 18 breast cancer cell lines were treated with the agonist or antagonists of the androgen receptor (AR). Among the 18 cell lines tested, only T-47D cells proliferated in an androgen-dependent manner, while the other cell lines were almost irresponsive to AR stimulation. On the other hand, treatment with AR antagonists at relatively high doses suppressed the proliferation of not only T-47D cells but also some other cell lines including AR-low/negative cells. In addition, expression of the full-length AR and constitutively active AR splice variants, AR-V7 and ARV567es, was not correlated with sensitivity to AR antagonists. These data suggest that the antiproliferative effect of AR antagonists is AR-independent in some cases. Consistently, proliferation of AR-knockout BT-549 cells was inhibited by AR antagonists. Identification of biomarkers would be necessary to determine which breast cancer patients will benefit from these drugs.

Collagen induction of immune cells in the mammary glands during pregnancy.

The mammary glands are dynamic tissues affected by pregnancy-related hormones during the pregnancy-lactation cycle. Collagen production and its dynamics are essential to the remodeling of the mammary glands. Alterations of the mammary microenvironment and stromal cells during the pregnancy-lactation cycle are important for understanding the physiology of the mammary glands and the development of breast tumors. In this study, we performed an evaluation of collagen dynamics in the mammary fat pad during the pregnancy-lactation cycle. Reanalysis of single-cell RNA-sequencing (scRNA-Seq) data showed the ectopic collagen expression in the immune cells and cell-cell interactions for collagens with single-cell resolution. The scRNA-Seq data showed that type I and type III collagen were produced not only by stromal fibroblasts but also by lymphoid and myeloid cell types in the pregnancy phase. Furthermore, the total cell-cell interaction score for collagen interactions was dramatically increased in the pregnancy tissue. The data presented in this study provide evidence that immune cells contribute, at least in part, to mammary collagen dynamics. Our findings suggest that immune cells, including lymphoid and myeloid cells, might be supportive members of the extracellular matrix orchestration in the pregnancy-lactation cycle of the mammary glands.NEW & NOTEWORTHY Our study evaluated mammary gland collagen dynamics during the pregnancy-lactation cycle using single-cell RNA-sequencing data. We found ectopic collagen expression in immune cells and an increase in collagen interactions during pregnancy. Type I and type III collagen were produced by lymphoid, myeloid, and stromal fibroblast cells during pregnancy. These findings suggest that immune cells, including lymphoid and myeloid cells, play a crucial role in supporting the extracellular matrix in mammary glands during pregnancy-lactation cycles.

Prognostic impact of the distance from the root of splenic artery to tumor in the patients with pancreatic body or tail cancer.

BACKGROUND: The impact of the distance from the root of splenic artery to tumor (DST) on the prognosis and optimal surgical procedures in the patients with pancreatic body/tail cancer has been unclear. METHODS: We retrospectively analyzed 94 patients who underwent distal pancreatectomy (DP) and 17 patients who underwent DP with celiac axis resection (DP-CAR) between 2008 and 2018. RESULTS: The 111 patients were assigned by DST length (in mm) as DST = 0: n = 14, 0

Potential utility of pretreatment serum miRNAs for optimal treatment selection in advanced high-grade serous ovarian cancer.

OBJECTIVE: The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy. METHODS: Consecutive patients with clinical stage IIIB-IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients. RESULTS: Of the 108 patients with stage IIIB-IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively. CONCLUSIONS: Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients.

Evaluation of ventral branches of segment VI portal vein relative to the right hepatic vein in laparoscopic right anterior sectionectomy.

INTRODUCTION: The right intersectional plane and the right hepatic hilum were noted too often exhibit anatomical variations, making difficult the laparoscopic right anterior sectionectomy (LRAS). METHODS: We analyzed the anatomical features employing 3D-CT images of 55 patients, and evaluated these features according to the course of ventral branches of segment VI of the portal vein (PV, P6a) relative to the right hepatic vein (RHV). RESULTS: P6a run on the dorsal side of RHV in 32 patients (58%, Dorsal-P6a) and the ventral side of RHV in 23 (42%, Ventral-P6a). Ventral-P6a had more patients with S6 partially drained by middle hepatic vein (MHV, 39% vs. 0%, P < 0001), the narrower angle between the anterior and posterior branches of PV (73.1° vs. 93.8°, P = 0.006), the wider angle between the RHV and inferior vena cava  (54.3° vs. 44.3°, P < 0.001), and more steeply pitched angle between S6 and S7 along the RHV (140.6° vs. 162.0°, P < 0.001) compared to Dorsal-P6a. CONCLUSION: In LRAS for Dorsal-P6a patients, the transection surface was relatively flat. In LRAS for Ventral-P6a patients, the narrow space between anterior and posterior glissons makes difficult the glissonean approach. The transection plane was steeply pitched, and RHV was partially exposed. S6 was often partially drained to MHV in 39% of the Ventral-P6a patients, which triggers congestion during liver transection of a right intersectional plane after first splitting the confluence of this branch.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Impact of hypoglycemia after gastrectomy on Global Leader Initiative on Malnutrition-defined malnutrition: a retrospective study.

PURPOSE: The Global Leader Initiative on Malnutrition (GLIM) criteria were developed in 2018 as a global indicator of malnutrition, and the term 'malnutrition-sarcopenia syndrome' was established. Recently, it has been reported that fluctuations in blood glucose are related to sarcopenia. In this study, we investigated the effects of glucose fluctuations on malnutrition after gastrectomy using a continuous glucose monitoring (CGM) device. METHODS: We analyzed the data of 69 patients with gastric cancer (GC) who underwent curative gastrectomy between November 2017 and December 2020. CGM was performed over a 2-week period at 1 month and 1 year after surgery. The GLIM criteria included weight loss, the body mass index (BMI), and the psoas muscle mass index (PMI). RESULTS: One year after surgery, 25 and 35 patients had severe and moderate malnutrition, respectively. The time below range (TBR) (percent of time the glucose concentration was < 70 mg/dL) and nocturnal (00:00-06:00) TBR were significantly higher in the severe malnutrition group than in the other groups (TBR: normal/moderate 17.9% vs. severe 21.6%, P = 0.039, nocturnal TBR; normal/moderate 30.6% vs. severe 41.1%, P = 0.034). CONCLUSIONS: Post-gastrectomy hypoglycemia, including long nocturnal hypoglycemia, was higher in severely malnourished patients than in other patients even 1 year after surgery. Prevention of nocturnal hypoglycemia may be the key to improving malnutrition following gastrectomy.

Use of accelerometry to detect varus thrust of osteoarthritic knees before and one year after high tibial osteotomy.

BACKGROUND: The purpose of this study was to determine the effects of high tibial osteotomy (HTO) on varus thrust during gait in patients with medial compartment knee osteoarthritis (KOA), and to identify factors that influence thrust before and one year after surgery. METHODS: HTO was performed in 60 KOA patients (70 knees, including 56 knees by open wedge and 14 by closed wedge). The control group comprised 28 normal, control subjects. Several parameters were evaluated before surgery and one year thereafter. Varus thrust was defined as acceleration of the thigh relative to the lower leg in the coronal plane. Knee-injury-and-osteoarthritis-outcome scores (KOOSs), knee joint angles, radiography, and mediolateral knee acceleration during free speed gait were measured and analyzed. RESULTS: One-year after HTO, KOOSs, knee extension angles, and range of knee motion were improved (p < 0.001). The hip-knee-ankle angle and joint-line-convergent angle (JLCA) had decreased (p < 0.001), and walking speed had increased (p < 0.001). Preoperatively, patient acceleration was significantly (p < 0.05) higher than that of controls, and it did not change after HTO. However, it was reduced significantly (p < 0.05) after adjusting for walking speed. Walking speed correlated significantly with acceleration preoperatively, postoperatively, and among controls. Surgical methods (open-wedge/closed-wedge HTO) and correction angle did not affect postoperative acceleration. There was a low correlation between acceleration and KOOSs (KOOSa, KOOSp), knee joint angles, or JLCA postoperatively, but no relationship was found between acceleration and these parameters in the preoperative or the control group. CONCLUSIONS: Walking speed correlated significantly with acceleration preoperatively, postoperatively, and with those of controls. Mediolateral acceleration of the thigh relative to the lower leg in patients with KOA was significantly higher than that of normal controls before surgery, and it did not change after HTO. However, after surgery it was reduced significantly after adjusting for walking speed.

Plasma microRNA-192-5p can predict the response to neoadjuvant chemotherapy and prognosis in esophageal cancer.

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. Recently, neoadjuvant chemotherapy (NAC) before curative surgery has become a standard treatment for clinical stage II or III EC patients. Some EC patients receive a complete response (CR) by NAC; thus, curative surgery may be unnecessary for such patients. MicroRNA levels in plasma have the potential to be a predictor of response to NAC. In the present study, we focused on miR-192-5p, which is highly expressed in EC tissue. The purpose was to investigate the correlations between levels of plasma miR-192-5p and the response to NAC. Furthermore, molecular functions of miR-192-5p associated with chemosensitivity were examined using EC cell lines. The levels of miR-192-5p in plasma before surgery were evaluated in 113 EC patients. Sixty-nine patients received NAC. miR-192-5p levels in the CR group were significantly higher than in the other groups (p = 0.002). The downregulation of miR-192-5p in the EC cell line inhibited sensitivity to cisplatin, and the overexpression of miR-192-5p in the EC cell line promoted sensitivity to cisplatin. miR-192-5p regulated sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR-192-5p could be used as a predictor of response to chemotherapy and prognosis in EC patients.

Small Extracellular Vesicles from adipose-derived stem cells suppress cell proliferation by delivering the let-7 family of microRNAs in ovarian cancer.

INTRODUCTION: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. MATERIALS AND METHODS: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis. RESULTS: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients. CONCLUSION: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs.

Aberrant accumulation of NIK promotes tumor growth by dysregulating translation and post-translational modifications in breast cancer.

BACKGROUND: In vivo investigations with cancer cells have powerful tools to discover cancer progression mechanisms and preclinical candidate drugs. Among these in vivo experimental models, the establishment of highly malignancy cell lines with xenograft has been frequently used. However, few previous researches targeted malignancy-related genes whose protein levels translationally changed. Therefore, this study aimed to identify malignancy-related genes which contributed to cancer progression and changed at the protein level in the in vivo selected cancer cell lines. METHODS: We established the high malignancy breast cancer cell line (LM05) by orthotopic xenograft as an in vivo selection method. To explore the altered genes by translational or post-translational regulation, we analyzed the protein production by western blotting in the highly malignant breast cancer cell line. Functional analyses of the altered genes were performed by in vitro and in vivo experiments. To reveal the molecular mechanisms of the regulation with protein level, we evaluated post-translational modification by immunoprecipitation. In addition, we evaluated translational production by click reaction-based purification of nascent protein. RESULTS: As a result, NF-κB inducing kinase (NIK) increased at the protein level and promoted the nuclear localization of NF-κB2 (p52) and RelB in the highly malignant breast cancer cell line. The functional analyses indicated the NIK upregulation contributed to tumor malignancy via cancer-associated fibroblasts (CAFs) attraction and partially anti-apoptotic activities. Additionally, the immunoprecipitation experiment revealed that the ubiquitination of NIK decreased in LM05 cells. The decline in NIK ubiquitination was attributed to the translational downregulation of cIAP1. CONCLUSIONS: Our study identified a dysregulated mechanism of NIK production by the suppression of NIK post-modification and cIAP1 translation. The aberrant NIK accumulation promoted tumor growth in the highly malignant breast cancer cell line.

Downregulating vaccinia-related kinase 1 by luteolin suppresses ovarian cancer cell proliferation by activating the p53 signaling pathway.

OBJECTIVES: Ovarian cancer constitutes one of the most common causes of cancer-related deaths, and preventing chemotherapy resistance and recurrence in patients with ovarian cancer remains a challenge. Herein, we aimed to identify the effect of luteolin, a novel therapeutic agent targeting vaccinia-related kinase 1 (VRK1), on high-grade serous ovarian cancer (HGSOC). METHODS: Phosphokinase array, RNA sequencing, and cell cycle and apoptosis assays were conducted to determine the underlying mechanism of the effect of luteolin on HGSOC cells. The anticancer effects of oral and intraperitoneal luteolin administration were assessed in patient-derived xenograft models via several methods, including the assessment of tumor size and immunohistochemistry of phospho-p53, phosphor-HistoneH3 and cleaved caspase 3. RESULTS: Luteolin reduced HGSOC cell proliferation and increased apoptosis and cell cycle arrest at G2/M. Compared with controls, several genes were dysregulated in luteolin-treated cells, and luteolin activated the p53 signaling pathway. The human phosphokinase array revealed distinct p53 upregulation in luteolin-treated cells, as confirmed by p53 phosphorylation at ser15 and ser46 using western blot analysis. In patient-derived xenograft models, oral or intraperitoneal luteolin administration substantially suppressed tumor growth. Moreover, combination treatment involving luteolin and cisplatin inhibited tumor cell proliferation, especially in cisplatin-resistant HGSOC cell lines. CONCLUSIONS: Luteolin demonstrated considerable anticancer effect on HGSOC cells, reduced VRK1 expression, and activated the p53 signaling pathway, thereby inducing apoptosis and cell cycle arrest in G2/M and inhibiting cell proliferation. Furthermore, luteolin exhibited a synergistic effect with cisplatin both in vivo and in vitro. Thus, luteolin can be considered a promising cotreatment option for HGSOC.

Novel therapeutic strategies targeting UCP2 in uterine leiomyosarcoma.

Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy. This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into mice to establish mouse models. In vivo analyses showed that proscillaridin A and lanatoside C exerted a superior antitumor effect. The results of mRNA sequencing showed that uncoupling protein 2 (UCP2) was suppressed in the sirtuin signaling pathway, increasing reactive oxygen species (ROS) and inducing cell death. Moreover, the downregulation of UCP2 induced ROS and suppressed ULMS cell growth. Furthermore, analyses using clinical samples showed that UCP2 expression was significantly upregulated in ULMS tissues than in myoma tissues both at the RNA and protein levels. These findings suggested that UCP2 is a potential therapeutic target and can contribute to the development of novel therapeutic strategies in patients with ULMS.

Postoperative liver dysfunction is associated with poor long-term outcomes in patients with colorectal cancer: a retrospective cohort study.

BACKGROUND: Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery. METHODS: We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I-IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction. RESULTS: Forty-eight (13.3%) colorectal cancer patients (Stages I-IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P < 0.001). Univariate and multivariate analyses using Cox's proportional hazards model revealed that postoperative liver dysfunction independently was a poor prognostic factor (P = 0.001, Hazard ratio 2.75, 95% CI: 1.54-4.73). CONCLUSIONS: Postoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction.

Impact of the preoperative clinical N stage on the prognosis of patients with colon cancer.

AIM: Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. METHOD: This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. RESULTS: Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p = 0.04). CONCLUSION: Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

Preoperative oral antibiotic administration in patients undergoing curative resection with stoma creation for colorectal cancer: effectiveness in preventing surgical site infection and the possibility of peristomal candidiasis induced by enterobacterial alteration.

AIM: There are many reports that preoperative oral antibiotics (OAs) are effective in preventing surgical site infections (SSIs) in colorectal surgery. However, there is no consensus on the optimal dose of OAs. In this study, we investigated the efficacy of OAs in preventing SSIs and the possibility that OAs induce enterobacterial alteration in the intestinal tract. METHOD: We performed a retrospective cross-sectional analysis of 389 patients who underwent R0 resection and stoma creation for colorectal cancer in our department between 2009 and 2020. We focused on the incidence of peristomal candidiasis (PSC) as an indicator of enterobacterial alteration and used kanamycin (KM) and metronidazole (MNZ) as the OAs. A low-dose group received 1000 mg/day of both KM and MNZ, and a high-dose group received 2000 mg/day of both KM and MNZ. RESULTS: SSI occurred in 60 of the 389 cases (15.4%). Regardless of stoma type, SSI was significantly more common in the non-OA group, while PSC was significantly less common. When examined by OA dose, the incidence of SSI was not significantly different between the low-dose and high-dose groups. However, PSC was significantly more common in the high-dose group than in the non-OA and low-dose groups. Analysis of bacterial and fungal levels in stool samples showed that bacterial levels after OAs were significantly lower than before OAs, while fungal levels increased. CONCLUSION: OAs significantly reduce SSI in colorectal cancer surgery. However, excess OAs were significantly associated with the occurrence of PSC without contributing to further reduction in SSI.

Assessment of commercial polymers with and without reactive groups using amino acid derivative reactivity assay based on both molar concentration approach and gravimetric approach.

The amino acid derivative reactivity assay (ADRA), an alternative method for testing skin sensitization, has been established based on the molar concentration approach. However, the additional development of gravimetric concentration and fluorescence detection methods has expanded its range of application to mixtures, which cannot be evaluated using the conventional testing method, the direct peptide reactivity assay (DPRA). Although polymers are generally treated as mixtures, there have been no reports of actual polymer evaluations using alternative methods owing to their insolubility. Therefore, in this study, we evaluated skin sensitization potential of polymers, which is difficult to predict, using ADRA. As polymers have molecular weights ranging from several thousand to more than several tens of thousand Daltons, they are unlikely to cause skin sensitization due to their extremely low penetration into the skin, according to the 500-Da rule. However, if highly reactive functional groups remain at the ends or side chains of polymers, relatively low-molecular-weight polymer components may penetrate the skin to cause sensitization. Polymers can be roughly classified into three major types based on the features of their constituent monomers; we investigated the sensitization capacity of each type of polymer. Polymers with alert sensitization structures at their ends were classified as skin sensitizers, whereas those with no residual reactive groups were classified as nonsensitizers. Although polymers with a glycidyl group need to be evaluated carefully, we concluded that ADRA (0.5 mg/ml) is generally sufficient for polymer hazard assessment.