Microstructural characterization and inductively coupled plasma-reactive ion etching resistance of Y2O3-Y4Al2O9 composite under CF4/Ar/O2 mixed gas conditions.

In the semiconductor manufacturing process, when conducting inductively coupled plasma-reactive ion etching in challenging environments, both wafers and the ceramic components comprising the chamber's interior can be influenced by plasma attack. When ceramic components are exposed to long-term plasma environments, the eroded components must be replaced. Furthermore, non-volatile reactants can form and settle on semiconductor chips, acting as contaminants and reducing semiconductor production yield. Therefore, for semiconductor processing equipment parts to be utilized, it is necessary that they exhibit minimized generation of contaminant particles and not deviate significantly from the composition of conventionally used Al2O3 and Y2O3; part must also last long in various physicochemical etching environment. Herein, we investigate the plasma etching behavior of Y2O3-Y4Al2O9 (YAM) composites with a variety of mixing ratios under different gas fraction conditions. The investigation revealed that the etching rates and changes in surface roughness for these materials were significantly less than those of Y2O3 materials subjected to both chemical and physical etching. Microstructure analysis was conducted to demonstrate the minimization of crater formation. Mechanical properties of the composite were also analyzed. The results show that the composite can be commercialized as next-generation ceramic component in semiconductor processing equipment applications.

Perinatal Outcomes and Neurodevelopment 1 Year after Birth in Discordant Twins According to Chorionicity.

Background and Objectives: This study aimed to compare maternal complications, perinatal outcomes, and neurodevelopment 1 year after the birth between concordant and discordant twins in monochorionic and dichorionic twins. Materials and Methods: This retrospective study included twin pregnancies delivered between 24 + 1 and 38 + 2 weeks of gestation between January 2011 and September 2019. Chorionicity was confirmed by ultrasonography and was categorized into monochorionic and dichorionic. Each was then divided into two groups (concordant and discordant) according to birth weight discordancy. Maternal complications and neonatal outcomes, including neurodevelopmental delays, were compared between the two groups. Results: A total of 298 pairs of twin pregnancies were enrolled, of which 58 (19.26%) women were pregnant with monochorionic diamniotic twins and 240 (80.54%) with dichorionic diamniotic twins. In both monochorionic and dichorionic twins, the discordant twins had a greater incidence of emergency deliveries because of iatrogenic causes than the concordant twins. Among dichorionic twins, discordant twins had lower birth weight rates and higher hospitalization rates and morbidities than concordant twins. Among monochorionic twins, discordant twins had a lower birth weight and higher neonatal mortality than concordant twins. The neonatal size was not a predictor of neurodevelopment in this group. Based on the logistic regression analysis, male sex, respiratory distress syndrome, and bronchopulmonary dysplasia were risk factors for the neurodevelopmental delay; birth weight discordancy was significant only in dichorionic twins. Conclusions: Perinatal outcomes in discordant twins may be poor, and neurodevelopment 1 year after birth was worse in discordant twins than in concordant twins. Discordancy in twins can be a risk factor for neurodevelopmental delay.

Antibody-mediated blockade for galectin-3 binding protein in tumor secretome abrogates PDAC metastasis.

The major challenges in pancreatic ductal adenocarcinoma (PDAC) management are local or distant metastasis and limited targeted therapeutics to prevent it. To identify a druggable target in tumor secretome and to explore its therapeutic intervention, we performed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis of tumors obtained from a patient-derived xenograft model of PDAC. Galectin-3 binding protein (Gal-3BP) is identified as a highly secreted protein, and its overexpression is further validated in multiple PDAC tumors and primary cells. Knockdown and exogenous treatment of Gal-3BP showed that it is required for PDAC cell proliferation, migration, and invasion. Mechanistically, we revealed that Gal-3BP enhances galectin-3-mediated epidermal growth factor receptor signaling, leading to increased cMyc and epithelial-mesenchymal transition. To explore the clinical impact of these findings, two antibody clones were developed, and they profoundly abrogated the metastasis of PDAC cells in vivo. Altogether, our data demonstrate that Gal-3BP is an important therapeutic target in PDAC, and we propose its blockade by antibody as a therapeutic option for suppressing PDAC metastasis.

Fetal intracranial hemorrhage and maternal vitamin K deficiency induced by total parenteral nutrition: A case report.

RATIONALE: Fetal brain hemorrhage is rare. It is caused mainly by maternal trauma or fetal coagulation disorder, but in some cases, vitamin K deficiency may be the cause. PATIENT CONCERNS: We describe the case of a pregnant woman with bowel obstruction who was susceptible to vitamin K deficiency due to oral diet restriction, decreased intestinal absorption, and limited intravenous vitamin K supplementation. DIAGNOSIS: After 18 days of intermittent total parenteral nutrition, acute onset of severe fetal brain hemorrhage developed. INTERVENTIONS: After acute onset of fetal brain hemorrhage, the patient underwent an emergency cesarean section at 25 + 3 weeks of gestation due to fetal non-reassuring fetal monitoring. OUTCOMES: The Apgar score at birth was 0/0, and despite cardiopulmonary resuscitation, neonatal death was confirmed. After the baby was delivered, we checked the maternal upper abdominal cavity and found a massive adhesion in the small bowel to the abdominal wall near the liver and stomach with an adhesion band. The adhesion band, presumably a complication of previous hepatobiliary surgery, appeared to have caused small bowel obstruction. Adhesiolysis between the small bowel and abdominal wall was performed. LESSONS: This case demonstrates that even relatively short-term total parenteral nutrition can cause severe fetal brain hemorrhage. Vitamin K supplementation is required for mothers who are expected to be vitamin K deficient, especially if they are on total parenteral nutrition for more than 3 weeks.

The predicting factors for indication of surgery in patients with hemoperitoneum caused by corpus luteum cyst rupture.

The aim of the study was to determine the risk factors for surgery in patients with hemoperitoneum caused by corpus luteum cyst rupture. A retrospective review of medical records of 155 patients diagnosed with hemoperitoneum caused by corpus luteum cyst rupture was conducted between January 2010 and March 2015. The patients were divided into two groups: surgical and conservative management. The differences in characteristics between the two groups were compared. The indicators that determine the need of a surgery at the initial visit were also compared between the two groups. Initial hemoglobin level was lower (11.3 ± 1.4 g/dL vs. 12.2 ± 1.2 g/dL; p = 0.007) in the surgery group. There were significant differences in posterior cul-de-sac (PCDS) fluid collection depth (6.2 ± 2.5 cm vs. 4.5 ± 1.6 cm, p = 0.000), total fluid collection depth (8.4 ± 1.8 cm vs. 6.5 ± 2.1 cm, p = 0.000), single deepest pocket depth (6.7 ± 2.2 cm vs. 5.1 ± 1.5 cm, p = 0.006), liver-dome fluid (78.9% vs. 35.6%; p = 0.002), and estimated intrapelvic bleeding amount (325 ± 250 cc vs. 206 ± 146.5 cc, p = 0.002). The extravasation over grade 2 was more often in surgery group (68.4% vs. 30.1%; p = 0.001). PCDS fluid collection depth, the presence of liver-dome fluid, and the severity of contrast extravasation through ultrasonography and computed tomography are good indicators for determining the management of hemoperitoneum resulting from corpus luteum cyst rupture in healthy women.

Original Articles Preoperative Hematological Parameters for Predicting Ovarian Torsion in Patients with Mature Cystic Teratoma.

OBJECTIVE: The objective of this study is to evaluate the preoperative hematological parameters to predict ovarian torsion in patients with ovarian mature cystic teratoma. We also analyzed the diagnostic value of these makers to predict ovarian necrosis in cases of torsion as well as the effect of torsion on ovarian reserve. PATIENTS AND METHODS: This is a retrospective study of 132 patients who received either laparoscopic or laparotomy surgery for OMCT at a single university hospital. Clinical characteristics and preoperative hematological parameters were compared between patients with or without torsion. Patients with torsion were further classified as infarction and non-infarction group. Preoperative parameters were compared between the two groups as well. RESULTS: White blood cell (WBC) count, neutrophil percent, neutrophil count, and neutrophil to lymphocyte ratio (NLR) were higher in the torsion group (n=37) than the non-torsion group (n=95) (p<0.05 for all). Although statistically insignificant, the preoperative anti-Mullerian hormone (AMH) was lower in the torsion group than the non-torsion group (4.07 ± 3.38 vs 6.1 ± 3.6, p=0.122). In cases of torsion, the infarction group showed higher WBC count and lymphocyte count but lower hemoglobin level and platelet to lymphocyte ratio (PLR) than the non-infarction group (p<0.05 for all). CONCLUSION: The WBC count, neutrophil percent, neutrophil count, and NLR were higher in the cases of OMCT with torsion, and these parameters may be useful to diagnose OMCT with torsion. Also, adnexal torsion may deteriorate ovarian reserved as indicated by decreased AMH in torsion group.

Antioxidant Activity of Sprouts Extracts Is Correlated with Their Anti-Obesity and Anti-Inflammatory Effects in High-Fat Diet-Fed Mice.

Obesity is closely associated with oxidative stress and chronic inflammation leading to related metabolic diseases. Some natural extracts or polyphenols reportedly possess anti-obesity and anti-inflammatory effects as well as antioxidant activity. In this study, we assessed the correlations between the antioxidant, anti-obesity, and anti-inflammatory activities of plant extracts with potent antioxidant activity in diet-induced obese mice. Sprouts of Cedrela sinensis (CS) and Oenothera biennis L. (OB) were selected as the most potent antioxidant plant based on analysis of in vitro antioxidant activity of the extracts of ten different edible plants. C57BL/6 mice were fed with a high-fat diet (HFD) and orally treated with 50% ethanol extract of CS or OB at 50 or 100 mg/kg body weight 5 days a week for 14 weeks. Body weight gain, weight of adipose tissue, adipocyte size, and levels of lipid metabolism, inflammation, and oxidative stress markers were investigated. The CS or OB extract reduced body weight gain, visceral adipose tissue weight, adipocyte size, and plasma leptin levels, and expressions of adipogenic genes (PPARγ and fatty acid synthase) in the adipose tissue and liver of HFD-fed mice. Both extracts also reduced mRNA levels of pro-inflammatory cytokines (IL-6 and TNF-α) and oxidative stress-related genes (heme oxygenase- (HO-) 1 and p40phox). Body weight gain of mice was significantly correlated with visceral adipose tissue weight and adipocyte size. Body weight gain and adipocyte size were significantly correlated with plasma total cholesterol and 8-epi PGF2α levels, mRNA levels of leptin, HO-1, p40phox, and CD-11 in the adipose tissue, and mRNA levels of TNF-α in the adipose tissue and liver. These results suggest that the CS and OB extracts with potent antioxidant activity may inhibit fat deposition in adipose tissue and subsequent inflammation.

The diagnosis of an imperforate anus in female fetuses.

Imperforate anus is an anomaly caused by a defect in the development of the hindgut during early pregnancy. It is a relatively common congenital malformation and is more common in males. Although there are cases of a solitary imperforate anus, the condition is more commonly found as a part of a wider spectrum of other congenital anomalies. Although urgent reconstructive anorectal surgery is not necessary, immediate evaluation is important and urgent decompressive surgery may be required. Moreover, as there are often other anomalies that can affect management, prenatal diagnosis can help in optimizing perinatal care and prepare parents through prenatal counseling. In the past, imperforate anus was diagnosed by prenatal ultrasonography based on indirect signs such as bowel dilatation or intraluminal calcified meconium. Currently, it is diagnosed by directly checking the perineum with prenatal ultrasonography. Despite advances in ultrasound technology, accurate prenatal diagnosis is impossible in most cases and imperforate anus is detected after birth. Here, we present two cases of imperforate anus in female fetuses that were not diagnosed prenatally.

Distribution pattern of tumor infiltrating lymphocytes and tumor microenvironment composition as prognostic indicators in anorectal malignant melanoma.

Anorectal malignant melanoma (ARMM) is a rare disease with poor prognosis. Determining ARMM prognosis precisely is difficult due to the lack of proper assessment techniques. Immunotherapy has proven effective against cutaneous malignant melanoma and may show efficacy in ARMM. Herein, we assessed the immune profile of ARMM to identify possible prognostic biomarkers. Twenty-two ARMM formalin-fixed and paraffin-embedded samples were evaluated using an nCounter® PanCancer Immune Profiling Panel. Validation was performed through immunohistochemical staining for CD3, CD8, Foxp3, CD68, CD163, and PD-L1. RNA analysis revealed significantly decreased scores for pathways involved in cell regulation and function, as well as chemokines, in recurrent patients compared to nonrecurrent patients. In cell-type profiling, the recurrent cases displayed significantly low tumor infiltrating lymphocyte (TIL) scores. Recurrence/death prediction models were defined using logistic regression and showed significantly lower scores in recurrent and deceased patients (all, P < 0.001) compared to those in nonrecurrent and surviving patients. The high total TIL and tumor-associated macrophage (TAM) groups had significantly better overall survival outcomes compared to the low total TIL and TAM groups (P = 0.007 and P = 0.035, respectively). In addition, the presence of CD3 + TILs in the invasion front was an independent favorable prognostic indicator (P = 0.003, hazard ratio = 0.21, 95% confidential interval, 0.01-0.41). Patients with inflamed or brisk-infiltration type tumors also had a significantly better overall survival than that of patients with immune-desert/excluded and absent/non-brisk type tumors (P = 0.03 and P = 0.0023, respectively). In conclusion, TILs have a strong prognostic value in ARMM, and the quantification of TILs and an analysis of the TIL phenotype and infiltration pattern during pathological diagnosis are essential to guide treatment strategies and accurate prognosis in ARMM.

The inhibitory effect of curcumin via fascin suppression through JAK/STAT3 pathway on metastasis and recurrence of ovary cancer cells.

BACKGROUND: Fascin is an actin-binding protein and highly expressed in ovarian cancer cells. It is associated with metastasis of cancer and may be a useful prognostic factor. Anticancer activity of curcumin is related to its effect on several signaling mechanisms. Although there have been many reports regarding the anticancer properties of curcumin, its inhibitory effects on migration and invasion of ovarian cancer cells, particularly in the context of fascin expression, have not been reported. The purpose of this study was to investigate the effect of curcumin on fascin expression in ovarian cancer cells and to propose a possible mechanism for the anticancer activity of curcumin through reduced fascin expression. METHODS: SKOV3, human epithelial ovary cancer cell line, was cultured with curcumin at various dose and duration. The fascin was quantified using cell viability test and Western blot. To determine the effect of curcumin on the upstream pathway of fascin expression, the signal transducer and activator of transcription 3 (STAT3) was analyzed by sandwich-ELISA. Attachment assay, migration assay and invasion assay were analyzed to approve the change of cellular invasiveness of ovary cancer after curcumin. To determine the morphological changes of ovarian cancer cells by curcumin, immunofluorescence was performed. RESULTS: MTS assays showed that cell viability was different at various concentration of curcumin, and as concentration increased, cell viability tended to decrease. Curcumin appears to suppress fascin expression, even with a minimal concentration and short exposure time. Also, curcumin may suppress fascin expression in ovarian cancer cells through STAT3 downregulation. The attachment assay, migration assay and invasion assay of the ovarian cancer cells exhibited a statistically significant decrease. Immunofluorescence revealed a change of cell shape from a typical form of uninfluenced cells to a more polygonal appearance, with a significant reduction in filopodia formation. CONCLUSIONS: Curcumin reduces fascin expression through JAK/STAT3 pathway inhibition, which interferes with the cellular interactions essential for the metastasis and recurrence of ovarian cancer cells. Higher curcumin concentrations and longer exposure times concomitantly decreased fascin expression.

A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer.

Preoperative chemoradiotherapy (PCRT) and subsequent surgery is the standard multimodal treatment for locally advanced rectal cancer (LARC), albeit PCRT response varies among the individuals. This creates a dire necessity to identify a predictive model to forecast treatment response outcomes and identify patients who would benefit from PCRT. In this study, we performed a gene expression study using formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 156 LARC patients (training cohort n = 60; validation cohort n = 96); we identified the nine-gene signature (FGFR3, GNA11, H3F3A, IL12A, IL1R1, IL2RB, NKD1, SGK2, and SPRY2) that distinctively differentiated responders from non-responders in the training cohort (accuracy = 86.9%, specificity = 84.8%, sensitivity = 81.5%) as well as in an independent validation cohort (accuracy = 81.0%, specificity = 79.4%, sensitivity = 82.3%). The signature was independent of all pathological and clinical features and was robust in predicting PCRT response. It is readily applicable to the clinical setting using FFPE samples and Food and Drug Administration (FDA) approved hardware and reagents. Predicting the response to PCRT may aid in tailored therapies for respective responders to PCRT and improve the oncologic outcomes for LARC patients.

Biliary intraductal tubule-forming neoplasm: a whole exome sequencing study of MUC5AC-positive and -negative cases.

AIMS: Biliary intraductal tubular neoplasms that are non-mucinous and negative for mucin 5AC (MUC5AC) are called intraductal tubulopapillary neoplasms (ITPNs). Intraductal tubular neoplasms with mucinous cytoplasm and MUC5AC positivity also occur and their nature remains unclear, although some pathologists may classify these as 'intraductal papillary neoplasms of the bile duct (IPNBs) of gastric type'. This study aimed to elucidate genetic features of biliary intraductal tubular neoplasms. METHODS AND RESULTS: Six resected cases of biliary intraductal neoplasm with >70% tubular configuration were characterised by clinicopathological examination and whole exome sequencing, and the findings obtained were compared between MUC5AC-negative (n = 2) and -positive cases (n = 4). The intraductal tumours consisted of the pancreatobiliary-type epithelium with high-grade dysplasia arranged in back-to-back tubules. Both of the two MUC5AC-negative cases were non-invasive neoplasms and developed in the liver, whereas all MUC5AC-positive cases had invasive carcinoma and were present in the intrahepatic (n = 2), perihilar (n = 1) and distal bile ducts (n = 1). In an exome-sequencing study, MUC5AC-negative cases harboured mutations in CTNNB1, SF3B1, BAP1 and BRCA1 (one case each). KRAS mutations were observed in three of four MUC5AC-positive cases (75%) but none of the MUC5AC-negative neoplasms. Compared to published data, known driver genes of other intraductal neoplasms of the pancreatobiliary system (e.g. APC, CTNNB1, STK11, GNAS and PIK3CA) were wild-type in all but one MUC5AC-negative case with CTNNB1 mutation. Chromatin modifiers (ARID1A, BAP1 and KMT2C) were also altered in MUC5AC-positive cases, similar to usual cholangiocarcinomas. CONCLUSIONS: This exome-sequencing study suggested that MUC5AC-negative biliary ITPNs are genetically distinct from pancreatic ITPNs and IPNBs. They may also biologically differ from MUC5AC-positive tubular neoplasms despite morphological resemblance.

A Multigene Model for Predicting Tumor Responsiveness After Preoperative Chemoradiotherapy for Rectal Cancer.

PURPOSE: Although preoperative chemoradiotherapy (PCRT) is regarded as a standard treatment for locally advanced rectal cancer, there is no reliable biomarker for predicting responsiveness to PCRT. We aimed to develop a biomarker model for predicting response to PCRT. METHODS AND MATERIALS: We included 184 patients who received PCRT followed by surgical resection and categorized them as good responders (complete or near-complete regression) or poor responders (all other patients). Candidate gene mRNAs were isolated from formalin-fixed paraffin-embedded tumor specimens and analyzed using the NanoString nCounter gene expression assay. Stepwise logistic regression analysis was used to select genes in discovery and training phases. A quantitative radio-responsiveness prediction model was developed and validated using internal cross-validation groups, and the model's predictive value was assessed based on the area under the receiver operating characteristic curve (AUC). RESULTS: By comparing the gene expressions between good and poor responders, we created a multigene mRNA model using FZD9, HRAS, ITGA7, MECOM, MMP3, NKD1, PIK3CD, and PRKCB. This panel showed good ability to predict treatment response (AUC: 0.846 for the whole data set). Internal cross-validation was performed to evaluate the model's predictive stability among 3 cohorts, which provided AUC values of 0.808-0.909. The satisfactory diagnostic performance of the radio-response prediction index persisted regardless of other clinicopathologic features such as clinical T or N stage, interval between radiation and surgery, and pretreatment carcinoembryonic antigen levels (P = .001, 95% CI, 0.686-0.905). CONCLUSIONS: We developed a multigene mRNA-based biomarker model that allows prediction of rectal cancer response to PCRT, which may help identify patients who will benefit most from PCRT.

Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas.

AIMS: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. METHODS AND RESULTS: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. CONCLUSIONS: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

Characterization of Hepatocellular Carcinoma Patients with FGF19 Amplification Assessed by Fluorescence in situ Hybridization: A Large Cohort Study.

BACKGROUND: FGF19 amplification is a relatively novel type of genetic aberration that has been proposed to be a driver of hepatocarcinogenesis. Selective inhibitors of FGFR4, a receptor of FGF19, have been developed as targeted therapies for hepatocellular carcinoma (HCC). Despite the role of FGF19 in mediating HCC progression, the clinicopathological characterization of patients exhibiting FGF19 amplification remains unclear. Immunohistochemical staining is the simplest and most widely used method of identifying aberrations in the FGF19 gene, although its specificity is very low. METHODS: This study investigated the prognostic significance of FGF19 amplification in a large cohort of 989 HCC patients using fluorescence in situ hybridization (FISH), which has a high degree of specificity. In addition, FISH data from formalin-fixed, paraffin-embedded sections were compared with copy number variation (CNV) data obtained from fresh frozen sections to validate the use of FISH as a diagnostic tool. RESULTS: FGF19 amplifications were detected by FISH in 51 (5.15%) of the 989 patients, and were independently associated with poor survival and a higher risk of tumor recurrence, as well as with poor prognostic factors such as a high α-fetoprotein level, hepatitis B or C virus infection, a large tumor size, microvascular invasion, and necrosis. In addition, FGF19 amplification was associated with TP53 mutation, and was mutually exclusive with CTNNB1 mutation. The results of the FISH and CNV analyses exhibited a significant concordance rate of 96% (κ = 0.618, p < 0.001). CONCLUSIONS: These data indicate that FGF19 amplification represents a unique molecular subtype associated with poor prognostic characteristics, which supports the hypothesis that the FGF19-FGFR4 signaling pathway plays an important role in hepatocarcinogenesis. We have also demonstrated that FISH is a viable alternative to CNV analysis, offering a number of advantages in the clinical setting.

Prediction of Recurrence With KRAS Mutational Burden Using Ultrasensitive Digital Polymerase Chain Reaction of Radial Resection Margin of Resected Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated. METHODS: KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation. RESULTS: KRAS mutation was detected in 76 patients (94%), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19% or greater was observed in 18 patients (22%). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses. CONCLUSIONS: KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.

Borage oil restores acidic skin pH by up-regulating the activity or expression of filaggrin and enzymes involved in epidermal lactate, free fatty acid, and acidic free amino acid metabolism in essential fatty acid-deficient Guinea pigs.

Borage oil (BO) reverses a disrupted epidermal lipid barrier and hyperproliferation in essential fatty acid deficiency (EFAD). However, little is known about its effect on skin pH, which is maintained by epidermal lactate, free fatty acids (FFAs), and free amino acids (FAAs) which is generated by lactate dehydrogenase (LDH), secreted phospholipase A2 (sPLA2), or filaggrin degradation with peptidylarginine deiminase-3 (PADI3). We hypothesized that BO restores skin pH by regulating epidermal lactate, FFA metabolism, or FAA metabolism in EFAD. To test this hypothesis, EFAD was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 weeks, followed by 2 weeks of a BO diet (group HCO + BO). As controls, groups HCO and BO were fed HCO or BO diets for 10 weeks. In group HCO + BO, skin pH, which was less acidic in group HCO, was restored; and epidermal lactate and total FFAs, including palmitate, stearate, linoleate, arachidate, behenate, and lignocerate, were higher than in group HCO. LDH and sPLA2 (mainly the PLA2G2F isoform) activities and protein expressions were similar between groups HCO + BO and BO. Epidermal acidic FAAs, as well as filaggrin and PADI3 protein and mRNA expressions were higher in group HCO + BO than in group HCO. Oleate, total FAAs including other FAAs, and LDH and sPLA2 mRNA expressions were not altered between groups HCO and HCO + BO. Basic FAAs were not altered among groups. Dietary BO restored acidic skin pH and increased epidermal levels of lactate, most FFAs, and acidic FAAs by up-regulating LDH, sPLA2, filaggrin, and PADI3 activities as well as protein or mRNA expressions in EFAD.

High-grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer.

AIMS: This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities. METHODS AND RESULTS: Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all seven cases examined. In resected specimens, high-grade PanIN was present chiefly in the main pancreatic duct, with longitudinal extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases, in which hypoechoic or hypovascular masses were observed on imaging, radiopathology correlations suggested that they represented parenchymal atrophy and subsequent fibrosis around affected ducts, but not invasive malignancy. On immunohistochemistry, the loss of p16 expression was found in five (50%), p53 overexpression in two (20%) and loss of SMAD4 expression in none (0%). KRAS mutations were detected in nine cases, with two dominant clones being found in three by ultrasensitive droplet digital polymerase chain reaction, suggesting the genetic heterogeneity of dysplastic cells composing individual lesions. Mutant GNAS was also observed in one case. CONCLUSIONS: Isolated high-grade PanIN may present with pancreatic duct stenosis. Therefore, intensive investigations including pancreatic juice cytology will be required for patients with unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD4 is infrequent, while GNAS may be mutated in premalignant lesions mainly affecting the main pancreatic duct, similar to KRAS.

Prediction of radio-responsiveness with immune-profiling in patients with rectal cancer.

We evaluate whether the tumor immune infiltrate (TIL) could be used for prediction of responsiveness to preoperative chemoradiotherapy (PCRT) in rectal cancers. Using formalin-fixed paraffin-embedded slides of pretreatment biopsies, co-stain for CD4, CD8, CD274 (PD-L1), FOXP3, cytokeratin, and DAPI was performed with Opal multi staining kit (Perkin-Elmer, Waltham, MA). Multispectral imaging and digital analysis to visualize and quantify specific immune infiltrates were performed using the Vectra imaging system (Perkin-Elmer). The density (number of cells per mm2) and proportion of total TILs and specific cell types in the stroma were calculated by inForm™ 2.2.1 software (Perkin-Elmer). The density and proportion of total TILs and specific cell types in the stroma were calculated by inForm™ 2.2.1 software (Perkin-Elmer, Waltham, MA). Patients were classified as group with total regression (TR, n = 25) and group with residual disease (near total, moderate, and minimal regression, RD, n = 50). The mean density of T cell infiltration and CD274 (PD-L1)+ lymphocyte were significantly higher in TR (p = 0.005, p = 0.001). The proportion of CD4+ lymphocyte (p=0.042) and CD274 (PD-L1)+ lymphocyte (p = 0.002) were different between 2 groups. The TR group has lower CD4+ and higher CD274 (PD-L1)+ proportions than RD group. The ratio among CD4+, CD8+, CD274 (PD-L1)+, FOXP3+ T cell was different between groups. TR group showed lower CD4/ CD274 (PD-L1) (p = 0.007), CD8/ CD274 (PD-L1) (p = 0.02), and FOXP3/ CD274 (PD-L1) (p = 0.003) ratio than RD group. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of responsiveness to PCRT.

Overcoming the learning curve of single-port total laparoscopic hysterectomy with barbed suture: a single surgeon's initial experience.

INTRODUCTION: Single-port total laparoscopic hysterectomy (TLH) has not been widely used because of its technical difficulty and steep learning curve, especially the laparoscopic suturing of the vaginal stump. Barbed suturing is a new technology that has the potential to greatly facilitate laparoscopic suturing. AIM: To compare surgical outcomes and vaginal vault healing between barbed sutures and traditional sutures in the repair of the vaginal vault during single-port TLH. MATERIAL AND METHODS: Between August 2013 and June 2015, we performed single-port TLH in 85 consecutive patients for benign or premalignant gynecological conditions. The first 48 patients underwent single-port TLH with traditional interrupted sutures, and the next 37 patients underwent single-port TLH with absorbable unidirectional knotless barbed sutures for repair of the vaginal vault. RESULTS: The patient characteristics (age, body mass index), procedures performed, uterine weight, and uterine disease were similar between the groups. There were no differences in blood loss, hemoglobin change, length of hospital stay, or perioperative complications. Operative time and the time required for vaginal cuff suturing were significantly shorter in the barbed suture group than in the traditional suture group (57.8 ±13.5 vs. 80.1 ±18.7 min, p < 0.001; 5.5 ±1.7 vs. 12.9 ±3.5 min, p < 0.001). Moreover, the use of barbed sutures significantly reduced the incidence of vaginal granulation tissue formation (2.7% vs. 35.4%, p < 0.001). CONCLUSIONS: Use of barbed sutures in single-port TLH reduced the operative time, suturing time of the vaginal vault, and formation of vaginal granulation tissue. Barbed suturing may help overcome surgical difficulties and vaginal cuff complications.