[A Case of Stage â £ Gastric Cancer Treated with Conversion Surgery after Chemotherapy].

A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric stenosis. Although open gastrectomy was planned the gastric cancer was unresectable due to pancreatic invasion and peritoneal dissemination. Cytology with abdominal lavage was CY0. She underwent gastrojejunostomy. She was treated by 19 courses of chemotherapy with SOX therapy for 2 years. The tumor reduced, and she underwent distal gastrectomy as conversion surgery. Pathological findings were por2>muc>tub2>tub1, ypT2(ypMP), INF c, int, Ly1a, V0, pPM0, pDM0, pN0(0/43), ypStage ⅠB, R0, Grade 2b. Adjuvant chemotherapy(S-1 and docetaxel)was administered after conversion surgery. She is alive without recurrence for 1 year and 6 months after gastrectomy. We report a case of Stage Ⅳ gastric cancer treated with conversion surgery after chemotherapy.

The diversity and abundance of gut microbiota are associated with the pain sensation threshold in the Japanese population.

Small fibre neuropathy (SFN) is an initial pathology of diabetic polyneuropathy (DPN). Serum lipopolysaccharide binding protein levels are positively correlated with the pain threshold in the foot, suggesting that the abundance of gut Gram-negative bacilli, which are a source of lipopolysaccharides, may be involved in the development of DPN. Furthermore, the abundance of the gut and oral microbiota is assumed to be involved in the pathogenesis of diabetes. Nevertheless, the association between SFN and the microbiota has not been clarified. A total of 1056 individuals were recruited in the 2018 Iwaki Health Promotion Project. Pain sensation was evaluated based on the pain threshold from intraepidermal electrical stimulation (PINT). Patients with PINT scores <0.15 mA were categorized into the low-PINT group (n = 718); otherwise, they were categorized into the high-PINT group (n = 283). Furthermore, each group was divided into the subjects with or without glucose tolerance based on HbA1c levels, fasting blood glucose levels and diabetic history. Principal coordinate analysis and α- and ß-diversity of the microbiota were evaluated. The correlation between clinical and microbiota data was examined. Oral microbiota diversity showed no structural differences according to PINT scores, whereas principal coordinate analysis and α- and ß-diversity revealed significant structural differences in gut microbiota (p < 0.01, p < 0.05 and p < 0.05, respectively), even after the participants with glucose intolerance were excluded (p < 0.01, p < 0.05 and p < 0.05, respectively). The relative abundance of the genus Bacteroides was significantly lower in high-PINT participants compared with low-PINT participants (10 ± 6.7% vs. 11.3 ± 7.0%, p < 0.01), even after the exclusion of subjects with diabetes and impaired fasting glucose (10.0 ± 6.5% vs. 11.2 ± 6.9%, p < 0.05). In univariate linear regression analyses, PINT was significantly correlated with metabolic syndrome parameters, eGFR, uric acid level and the abundance of Bacteroides. The correlation between Bacteroides and PINT scores remained significant after adjustment for multiple factors (ß = -0.07181, p < 0.05). Changes of bacterial diversity and a low abundance of gut Bacteroides were correlated with elevated PINT scores in the Japanese population. This correlation may represent a new therapeutic option for SFN.

Development of a Biomarker-Based Scoring System Predicting Early Recurrence of Resectable Pancreatic Duct Adenocarcinoma.

BACKGROUND: Resectable pancreatic ductal adenocarcinoma (R-PDAC) often recurs early after radical resection, which is associated with poor prognosis. Predicting early recurrence preoperatively is useful for determining the optimal treatment. PATIENTS AND METHODS: One hundred and seventy-eight patients diagnosed with R-PDAC on computed tomography (CT) imaging and undergoing radical resection at Hirosaki University Hospital from 2005 to 2019 were retrospectively analyzed. Patients with recurrence within 6 months after resection formed the early recurrence (ER) group, while other patients constituted the non-early recurrence (non-ER) group. Early recurrence prediction score (ERP score) was developed using preoperative parameters. RESULTS: ER was observed in 45 patients (25.3%). The ER group had significantly higher preoperative CA19-9 (p = 0.03), serum SPan-1 (p = 0.006), and CT tumor diameter (p = 0.01) compared with the non-ER group. The receiver operating characteristic (ROC) curve analysis identified cutoff values for CA19-9 (133 U/mL), SPan-1 (78.2 U/mL), and preoperative tumor diameter (23 mm). When the parameter exceeded the cutoff level, 1 point was given, and the total score of the three factors was defined as the ERP score. The group with an ERP score of 3 had postoperative recurrence-free survival (RFS) of 5.5 months (95% CI 3.02-7.98). Multivariate analysis for ER-related perioperative and surgical factors identified ERP score of 3 [odds ratio (OR) 4.63 (95% CI 1.82-11.78), p = 0.0013] and R1 resection [OR 3.20 (95% CI 1.01-10.17), p = 0.049] as independent predictors of ER. CONCLUSIONS: For R-PDAC, ER could be predicted by the scoring system using preoperative serum CA19-9 and SPan-1 levels and CT tumor diameter, which may have great significance in identifying patients with poor prognoses and avoiding unnecessary surgery.

Effects of the new fasting standard on sedation in the pediatric emergency room.

BACKGROUND: This study compared adherence to the fasting-time guidelines of the International Committee for the Advancement of Procedural Sedation (ICAPS) and the North American Society of Anesthesiologists (ASA) and complication rates in pediatric patients requiring procedure sedation and analgesia during treatment in the emergency room (ER). METHODS: This retrospective, single-center study was performed between 2016 and 2020, and enrolled patients who received procedural sedation and analgesia in the ER with the fasting times recommended in the ICAPS and ASA guidelines. RESULTS: In total, 857 patients were included. The most frequent indication for procedural sedation and analgesia was fracture reduction in 420 patients (49.0%). Ketamine, the most commonly administered drug, was given to 710 patients (82.8%). Adherence to the ICAPS guidelines was higher (P < 0.01), with 772 (95.7%) and 351 (41.0%) patients, respectively, adhering to the ICAPS and ASA recommendations for food and drink fasting times. Complications occurred in 130 patients (15.2%), including SpO2 <90% in 75 patients (8.7%) and vomiting in 20 patients (2.3%). No serious complications, such as aspiration, cardiac arrest, or death, occurred. The complication rate between the two groups did not differ significantly, with 50 (14.2%) and 127 (15.5%) patients experiencing complications according to the ICAPS and ASA guidelines, respectively (P = 0.586). CONCLUSIONS: The fasting recommendations of the ICAPS guidelines, which propose risk stratification to determine the appropriate fasting time for procedural sedation and analgesia, are more tolerable to patients and the rate of adverse events did not appear to be different from that experienced when following the ASA guidelines.

Inhibitory effects of xanthine oxidase inhibitor, topiroxostat, on development of neuropathy in db/db mice.

Inflammation and oxidative stress contribute to the pathophysiology of diabetic neuropathy. According to recent evidence, the modulation of macrophage polarization in peripheral nerves represents a potential therapeutic target for diabetic neuropathy. Xanthine oxidase, which is a form of xanthin oxidoreductase, is the rate-limiting enzyme that catalyzes the degradation of hypoxanthine and xanthine into uric acid. Activation of xanthine oxidase promotes oxidative stress and macrophage activation. A preclinical study reported the beneficial effects of xanthine oxidase inhibitors on peripheral nerve dysfunction in experimental models of diabetes. However, the detailed mechanisms remain unknown. In this study, we examined the effect of the xanthine oxidase inhibitor topiroxostat on macrophage polarization and peripheral neuropathy in an obese diabetic model, db/db mice. First, the effects of xanthine oxidase inhibitors on cultured macrophages and dorsal root ganglion neurons exposed to xanthine oxidase were assessed. Furthermore, five-week-old db/db mice were administered the xanthine oxidase inhibitors topiroxostat [1 mg/kg/day (dbT1) or 2 mg/kg/day (dbT2)] or febuxostat [1 mg/kg (dbF)]. Glucose metabolism and body weight were evaluated during the experimental period. At 4 and 8 weeks of treatment, peripheral nerve functions such as nerve conduction velocities, thermal thresholds and pathology of skin and sciatic nerves were evaluated. The mRNA expression of molecules related to inflammation and oxidative stress was also measured in sciatic nerves. Untreated db/db mice and the nondiabetic db strain (db/m) were studied for comparison. An in vitro study showed that topiroxostat suppressed macrophage activation and proinflammatory but not anti-inflammatory polarization, and prevented the reduction in neurite outgrowth from neurons exposed to xanthine oxidase. Neuropathic changes exemplified by delayed nerve conduction and reduced intraepidermal nerve fiber density developed in db/db mice. These deficits were significantly prevented in the treated group, most potently in dbT2. Protective effects were associated with the suppression of macrophage infiltration, cytokine expression, and oxidative stress in the sciatic nerve and decreased plasma xanthine oxidoreductase activity. Our results revealed the beneficial effects of the xanthine oxidase inhibitor topiroxostat on neuropathy development in a mouse model of type 2 diabetes. The suppression of proinflammatory macrophage activation and oxidative stress-induced damage were suggested to be involved in this process.

Short-term outcomes of robotic-assisted laparoscopic versus laparoscopic lateral lymph node dissection for advanced lower rectal cancer.

BACKGROUND: Therapeutic strategies to suppress local recurrence, including lateral lymph node metastasis, are important to improve the curability of rectal cancer. The aim of the present study was to clarify the advantages of robotic-assisted laparoscopic lateral lymph node dissection (RALLD), comparing its short-term outcomes with those of laparoscopic lateral lymph node dissection (LLLD). There are some retrospective reports comparing RALLD or LLLD and open lateral lymph node dissection (OLLD), but few reports comparing RALLD and LLND to each other. METHODS: From November 2014 to August 2020, we compared the short-term outcomes in 40 patients who underwent RALLD and 55 patients who underwent LLLD. RESULTS: The total operative time was significantly longer in the RALLD group than in the LLLD group (p < 0.001). However, lateral dissection time was not significantly different between the groups (p = 0.661). The postoperative hospital time was shorter in the RALLD group than in the LLLD group (p < 0.048). No significant differences were identified in the rates of postoperative bleeding, incisional surgical site infection (SSI), organ/space SSI, urinary disfunction, urinary infection, or small bowel obstruction between the groups. However, anastomotic leakage was significantly lower in the RALLD group than in the LLLD group (p = 0.031). CONCLUSIONS: The short-term outcomes of RALLD indicate it is feasible, and RALLD may be a useful modality for lower rectal cancer.

Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma.

Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC. The activation of cultured mouse PSCs was evaluated by qPCR. The induction of epithelial mesenchymal transition (EMT) in PDAC cell lines was assessed under stimulation with culture supernatant from activated PSCs. A total of 155 surgically resected PDAC subjects (83 nondiabetic, 18 with ≦3-years and 54 with >3-years history of diabetes) were clinicopathologically evaluated. A high-fat diet increased the expression of activated markers in cultured PSCs, which was abrogated by RAGE deletion. Culture supernatant from activated PSCs facilitated EMT of PDAC cells with elevation of TGF-ß and IL-6, but not from RAGE-deleted PSCs. Diabetic subjects complicated with metabolic syndrome, divided by cluster analysis, showed higher PSC activation and RAGE expression. In such groups, PDAC cells exhibited an EMT nature. The complication of metabolic syndrome with diabetes significantly worsened disease-free survival of PDAC subjects. Thus, RAGE in PSCs can be viewed as a new promoter and a future therapeutic target of PDAC in diabetic subjects with metabolic syndrome.

[A Case of Descending Colon and Rectal Cancer with Acute Myeloid Leukemia Performed Robot‒Assisted Hartmann's Procedure].

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. A second course of CAG therapy was started 15 days postoperatively. However, he was then diagnosed with exacerbation of the AML; remission induction therapy (daunorubicin, cytarabine)was started in November. In December, he developed a fever and abdominal pain, and on CT scan, it was discovered that an abscess had formed around the rectal resection site. Myelosuppression from AML led to prolonged sepsis; and by January 2020, the sepsis was systemic. His actual cause of death was given as circulatory failure. We report this, because only a few cases on the treatment of overlapping AML and colorectal cancers can be found in the literature.

Organ/space infection is a common cause of high output stoma and outlet obstruction in diverting ileostomy.

BACKGROUND: The objectives of this study are to identify causes of high-output stoma (HOS) and outlet obstruction (OO), which are major complications of diverting ileostomy. METHODS: A retrospective analysis was performed in 103 patients who underwent colorectal surgery and diverting ileostomy between December 2015 and November 2018. RESULTS: HOS was found in 32 patients (31.1%) and OO in 19 (18.4%). Organ/space surgical site infection (SSI), anastomotic leakage and OO were significant HOS-related factors in univariate analysis, and OO (odds ratio [OR] 3.39, p = 0.034) was a independent HOS-related factor in multivariate analysis. Organ/space SSI and male were significant OO-related factors in univariate analysis, and organ/space SSI (OR 3.77, p = 0.018) was a independent OO-related factor in multivariate analysis. The white blood cell (WBC) count on postoperative day (POD) 3 was significantly higher in the HOS group compared to the non-HOS group (9765 vs. 8130 /mL, p < 0.05), and the WBC count (9400 vs. 7475 /mL, p < 0.05) and C-reactive protein level (6.01 vs. 2.92 mg/L, p < 0.05) on POD 6 were significantly higher in the OO group compared to the non-OO group. CONCLUSION: Organ/space infection is involved in the common pathology of HOS and OO. Decreased intestinal absorption due to intestinal edema caused by organ/space SSI and relative stenosis at the abdominal wall-penetrating site are major causes of HOS and OO.

[Gallbladder Cancer with Multiple Liver Metastases Completely Responding to Gemcitabile plus Cisplatin Chemotherapy-A Case Report].

A 59-year-old man was diagnosed with cholecystolithiasis and cholecystitis and underwent cholecystectomy. The pathological findings were moderately differentiated adenocarcinoma(pT2)in the gallbladder fundus. Sixteen days after surgery, he visited our hospital due to jaundice. Abdominal enhanced CT and EOB-MRI revealed multiple liver metastases and lymph node metastases in the hepatoduodenal ligament that we deemed to be unresectable. A metallic stent was inserted for bile duct obstruction, and he underwent chemotherapy with gemcitabine plus cisplatin(GC). After 12 courses of GC, the metastatic lesions disappeared, and the patient showed complete response. FDG-PET/CT showed FDG uptake in the hepatoduodenal ligament and we subsequently decided to perform surgery. He underwent resection of the extrahepatic bile duct and regional lymphadenectomy. The pathological findings revealed no residual carcinomas in the bile duct or lymph nodes. We are continuing chemotherapy at present, and the patient is alive with no signs of recurrence at 1 year and 3 months following the diagnosis of multiple liver metastases.

[A Case of Liver Recurrence of Choriocarcinoma and AFP-Producing Carcinoma of the Stomach Showing a Complete Histological Response after Chemotherapy].

A 65-year-old man was hospitalized for gastric cancer. Abdominal computed tomography detected lower gastric cancer and invasion of the liver. Initial laboratory data showed high levels of serum AFP(2,688.6 ng/mL). He underwent distal gastrectomy with left lobectomy of the liver and cholecystectomy. Histology confirmed that the tumor consisted of 2 components: primary gastric choriocarcinoma and AFP-producing carcinoma. The pathological staging was pT4b(liver), N3aM0, Stage ⅢC. After surgery, AFP levels decreased to within the normal limits. Adjuvant chemotherapy(S-1)was administered for 1 year after the operation. Fourteen months later, PET-CT and EOB-MRI detected liver recurrence. He was treated with weekly paclitaxel(PTX)chemotherapy for the liver recurrence. After 12 courses, the tumor had disappeared. The patient was continuously treated with weekly PTX and is doing well without recurrence 24 months after the resection of the liver tumor. Co-existence of primary gastric choriocarcinoma and AFP-producing carcinoma is very rare. We report a case of liver recurrence of choriocarcinoma and AFP-producing carcinoma of the stomach showing a complete histological response after chemotherapy.

[Successful Treatment of Necrotizing Fasciitis Due to Ascending Colon Cancer-A Case Report].

A 70-year-old woman was brought to our hospital by ambulance because of severe groin pain on the right side. Computed tomography scan revealed a tumor in the ascending colon, intraperitoneal abscess spread to the subcutaneous tissues, and a large amount of pneumoderma. She was diagnosed with necrotizing fasciitis caused by penetration of ascending colon cancer and underwent lavage and drainage, right hemicolectomy, end ileostomy, and debridement of necrotic tissues on emergency. Postoperatively, she underwent debridement and irrigation at the bedside every day, but the necrotizing tissues spread. Debridement under general anesthesia was repeated on postoperative day 8. On postoperative day 20, negative pressure wound therapy(NPWT)was initiated to manage the exudates and wound condition, and healthy granulation tissues formed gradually. After 4 weeks, she underwent split-thickness skin graft implantation. The postoperative course was uneventful, and she was discharged from the hospital. She is currently on chemotherapy and has been alive for 1 year and 3 months after the first operation.

[A Case of Perforated Gastric Cancer Treated with Curative Resection Following Conservative Medical Management and Chemotherapy].

Perforated gastric cancer typically requires life-saving emergency surgery. However, preoperative diagnosis is difficult, the rate of radical resection is low, and the prognosis remains poor. Perforated gastric cancer is generally treated with 1- or 2- stage gastrectomy, but radical resection is rarely performed after a conservative medical management and chemotherapy for perforated gastric cancer. A 65-year-old man visited another hospital with left upper abdominal pain. He was diagnosed with upper GI perforation, and conservative medical management was selected because peritonitis was limited. After close examination, a Type 3 tumor was found in the cardiac region of the stomach. As the advanced gastric cancer was unresectable, chemotherapy, comprising4 courses of SP plus T-mab, was subsequently administered. As the therapeutic effect was PR, we performed total gastrectomy. The pathological findings were tub2>tub1>por2: pT2N1CY0H0P0M0, pStageⅡ, and we achieved curative resection. Postoperatively, S-1 treatment was performed as an adjuvant chemotherapy. The patient remains alive, without recurrence, for 3 years and 6 months postoperatively.

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination after Gastrectomy Effectively Treated with Combination Chemotherapy of Ramucirumab and Paclitaxel].

The REGARD and RAINBOW trials revealed the effectiveness of ramucirumab(RAM)for advanced gastric cancer patients who had been previously treated with chemotherapy. In the latest Japanese gastric cancer treatment guidelines, PAM plus paclitaxel(PTX)was positioned as a second-line chemotherapy for advanced gastric cancer. We report a case of advanced gastric cancer with peritoneal dissemination after gastrectomy effectively treated with RAM plus PTX. A 66-year-old woman underwent total gastrectomy with D2 lymph node dissection, splenectomy, and distal pancreatectomy. The pathological diagnosis was poorly differentiated adenocarcinoma, pT4b(pancreas), N3b, P1, CY1, Stage Ⅳ. She was treated with postoperative chemotherapy of S-1 plus cisplatin. However, 5 months after surgery, computed tomography(CT)showed ascites and recurrence of peritoneal dissemination. Cytological examination showed adenocarcinoma cells in the ascites. She was treated with combination chemotherapy of RAM and PTX as second line chemotherapy. After 1 course of this therapy, CT revealed complete disappearance of ascites and significant reduction in the size of the peritoneal dissemination. The patient survived without progression for 8 months after the recurrence was detected.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

Antimicrobial properties of poly (vinyl alcohol) films with zeolitic imidazolate framework (ZIF-8) nanoparticles for food packaging.

Antimicrobial packaging films are of interest to the fresh produce industry due to the high number of foodborne illness outbreaks associated with these products. This study evaluated the antimicrobial effectiveness of poly (vinyl alcohol) (PVA) films with embedded zeolitic imidazolate framework (ZIF-8) nanoparticles carrying trans-cinnamaldehyde (TC) against Escherichia coli MG1655 in spinach leaves. PVA films were synthesized using distilled water and mixed at 90°C for 1 h. The synthesized nanoparticles were introduced at various mass ratio concentrations (0%-5% weight of ZIF-8@TC nanoparticles to PVA), namely PVA-Z8-0 (control) through PVA-Z8-5. The PVA and ZIF-8@TC solution was mixed for 24 h until it seemed homogenous, cast, and dried in a ventilated oven at 35°C for 24 h. The release rate of TC from the PVA/ZIF-8@TC into both ethanol and methanol was characterized using HPLC methods. Disk diffusion and growth studies were performed to quantify the films antimicrobial effectiveness. Disk diffusion test showed that antimicrobial activity against E. coli MG1655 increased (p < 0.05) with increased nanoparticles concentration. Growth characteristics were described by the Baranyi model with some variations. About 0.26, 0.73, and 1.65 log reductions were achieved with the PVA-Z8-1 to PVA-Z8-3 films, respectively, while total inactivation was achieved with both the PVA-Z8-4 and PVA-Z8-5 films (p < 0.05). Similarly, the Baranyi model described the inhibitory profiles of the different films. This study contributes to the overall food safety body of knowledge regarding fresh produce and other packaged foods through the development of biopolymeric films with embedded nanoparticles to entrap natural antimicrobials. PRACTICAL APPLICATION: This study paves the way for further research on the development of active polymeric films for food packaging applications.

Properties of poly (vinyl alcohol) films with embedded zeolitic imidazolate framework (ZIF-8) nanoparticles for food packaging applications.

This study evaluated the physical, mechanical, barrier properties, and transition temperatures of poly (vinyl alcohol) (PVA) films with embedded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles carrying a natural antimicrobial, trans-cinnamaldehyde (TC). The ZIF-8 nanoparticles were synthesized using a sonochemical method and incorporated into polymeric matrices at mass ratio concentrations of 0% (control film) to 5% weight of ZIF-8@TC to PVA. Solutions were mixed, cast onto Petri dishes and dried for 12 h at 37°C in a ventilated oven. The film samples were stored in airtight containers at room temperature and used within 1 week. The engineering properties of the PVA/ZIF-8@TC films were compared with those of low-density polyethylene (LDPE) film commonly used for packaging of spinach leaves. The glass transition, melting, and crystallization temperatures of PVA compositive films all increased (p < 0.05) with ZIF-8@TC concentration. When exposed to high relative humidity environments, the PVA/ZIF-8@TC films had lower equilibrium moisture content (p < 0.05) than the LDPE film. Although the composite films have different tensile properties from the LDPE film, embedding ZIF-8@TC into PVA films improved the tensile strength by 17%, making the PVA/ZIF-8@TC films suitable for low load-bearing applications such as food packaging. The gas barrier properties of PVA-based films differed only slightly with added ZIF-8@TC (p < 0.05). PRACTICAL APPLICATION: PVA/ZIF-8@TC films are appropriate environment-friendly alternatives to polymeric food packaging in terms of their functional properties.

Diabetes mellitus impacts on expression of DNA mismatch repair protein PMS2 and tumor microenvironment in pancreatic ductal adenocarcinoma.

AIMS/INTRODUCTION: The mismatch repair (MMR) protein recognizes DNA replication errors and plays an important role in tumorigenesis, including pancreatic ductal adenocarcinoma (PDAC). Although PMS2, a MMR protein, is degraded under oxidative stress, the effects of diabetes are still unclear. Herein, we focused on whether diabetes affected MMR protein expression in PDAC. MATERIALS AND METHODS: Tissues from 61 surgically resected PDAC subjects were clinicopathologically analyzed. Immunohistochemical analysis was performed for MMR protein expression, oxidative stress, and immune cell infiltration. The change of MMR protein expression was assessed in PDAC cell lines under stimulation with 25 mM glucose and 500 µM palmitic acid. Survival curves were analyzed by the Kaplan-Meier method with the log-rank test. RESULTS: Diabetes complicated with dyslipidemia significantly decreased the expression of PMS2 in PDAC tissues with an inverse correlation with the degree of oxidative stress. Palmitic acid combined with high glucose induced degradation of PMS2 protein, enhancing oxidative stress in vitro. CD8+ T-cell infiltration was associated with a short duration of type 2 diabetes (≤4 years) and a low expression of PMS2 in PDAC tissues, while CD163+ tumor-associated macrophage infiltration was increased with a long duration of diabetes (>4 years). A short duration of diabetes exhibited a better prognosis than nondiabetic subjects with PDAC (P < 0.05), while a long duration of diabetes had a worse prognosis (P < 0.05). CONCLUSIONS: The different phases of diabetes have a major impact on PDAC by altering PMS2 expression and the tumor immune microenvironment, which can be targeted by an immune checkpoint inhibitor.

Dual epigenetic changes in diabetes mellitus-associated pancreatic ductal adenocarcinoma correlate with downregulation of E-cadherin and worsened prognosis.

Diabetes mellitus (DM) is a risk factor for pancreatic ductal adenocarcinoma (PDAC) that promotes the promoter methylation of CDH1. It is still unclear whether DM can exert other epigenetic effects, such as altering microRNA (miR) expression, in PDAC. The expression of miR-100-5p is known to be changed in DM patients and can suppress the expression of E-cadherin. In this study, the correlation between DM status and dual epigenetic changes was evaluated in PDAC specimens from patients who underwent radical surgical resection. A total of 132 consecutive patients with PDAC were clinicopathologically evaluated. E-cadherin and nuclear ß-catenin expression was measured using immunohistochemistry. DNA and miRs were extracted from the main tumor site on formalin-fixed paraffin-embedded tissue sections. TaqMan miR assays were applied to assess miR-100-5p expression. Bisulfite modification was conducted on the extracted DNA, which was then subjected to methylation-specific polymerase chain reaction. Immunohistochemistry revealed that decreased E-cadherin expression and increased nuclear ß-catenin expression were significantly associated with DM and poor tumor cell differentiation. The presence of long-duration DM (≥3 years) was a significant factor contributing to CDH1 promoter methylation (p < 0.01), while miR-100-5p expression was proportionally correlated with the preoperative HbA1c level (R = 0.34, p < 0.01), but not the duration of DM. The subjects with high miR-100-5p expression and CDH1 promoter methylation showed the highest level of vessel invasion and prevalence of tumor size ≥30 mm. PDAC subjects with dual epigenetic changes showed poorer overall survival (OS) than those with a single epigenetic change. miR-100-5p expression ≥4.13 and CDH1 promoter methylation independently predicted poor OS and disease-free survival (DFS) in the multivariate analysis. OS and DFS worsened in DM subjects with both HbA1c ≥ 6.5% and DM duration ≥3 years. Thus, DM is associated with two modes of epigenetic change by independent mechanisms and worsens prognosis.