Oncocytic Type Has Distinct Immunohistochemical and Recurrence-Free Survival than Other Histologic Types of the Intraductal Papillary Neoplasm of the Bile Duct.

Although intraductal oncocytic papillary neoplasm (IOPN) was considered distinct from the intraductal papillary neoplasm of the pancreas, the oncocytic histologic type remained as a subtype of intraductal papillary neoplasms of the bile duct (IPNBs) with gastric, intestinal, and pancreatobiliary types based on the fifth edition of the WHO classification. To test the characteristics of the oncocytic type of IPNBs, the histopathologic, immunohistochemical (Hep Par-1 and CD117), and clinical characteristics of 13 oncocytic type were compared with 114 others (15 gastric, 39 pancreatobiliary, and 60 intestinal) IPNB types. The oncocytic type, which occupied about 9% of IPNBs, was more frequent in females (p <0.05) and larger (mean, 5.3 vs. 3.6 cm; p <0.002) than other IPNB types. Immunohistochemically, the oncocytic type had more frequent and combined Hep Par-1 and CD117 expression than other IPNB types, (all p <0.05). The recurrence-free survival rate for patients with the oncocytic type (5-year survival, 100%) was significantly higher (p = 0.015) than for those with other histologic types (59.9%). The oncocytic type had distinct histopathologic, immunohistochemical, and survival outcomes from other IPNBs. Therefore, it can be separated from other IPNB types and classified as one independent entity, similar to IOPN of the pancreas.

Enteroblastic cholangiocarcinoma: An uncommon, underrecognized subtype of bile duct cancer.

Enteroblastic carcinoma is clinically characterized by an elevated serum level of alpha-fetoprotein (AFP) and is histologically characterized by cancer cells with a clear cytoplasm and 'blastic' coarse chromatin. It sometimes has an element of hepatoid carcinoma; therefore, these two neoplasms are often regarded as sister entities. Although hepatoid carcinoma in the biliary tree has been reported, enteroblastic cholangiocarcinoma is extremely uncommon. In the present study, four cases of enteroblastic cholangiocarcinoma were examined. Tumors were located inside the liver (n = 2) or common bile duct (n = 2). The two intrahepatic cases had a history of primary sclerosing cholangitis, and serum AFP levels were elevated in both. One unresectable case was diagnosed by needle liver biopsy, while the remaining three underwent surgical resection. Histologically, all cases showed similar microscopic features. Cuboidal or polygonal cancer cells with the characteristic clear cytoplasm and subnuclear vacuoles were arranged in a papillary, micropapillary, tubular, or solid architecture. One case had an element of pancreatobiliary-type adenocarcinoma, while a hepatoid carcinoma element was not observed in any cases. All cases were positive for AFP, glypican 3, and SALL4, with SALL4 being the most widely expressed. Heppar-1 and arginase-1 were negative, except for one case, which was positive for Heppar-1. In conclusion, enteroblastic cholangiocarcinoma is an uncommon subtype of biliary tract malignancy. These cases may have been categorized as 'clear cell' cholangiocarcinoma. Although enteroblastic cholangiocarcinoma seems to occur more commonly in extrahepatic regions, including the gallbladder, it may also develop in the liver, particularly in patients with primary sclerosing cholangitis.

Investigation of artificial intelligence integrated fluorescence endoscopy image analysis with indocyanine green for interpretation of precancerous lesions in colon cancer.

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

Prognostic significance of extranodal extension of nodal metastasis in adenocarcinoma of the ampulla of Vater.

Although nodal metastasis (NM) is an important prognostic factor of ampullary adenocarcinoma, the prognostic implication of extranodal extension (ENE) is not well characterized. NM with ENE status was investigated in 279 surgically resected ampullary adenocarcinoma patients and compared with other clinicopathologic factors, including overall survival (OS) and recurrence-free survival (RFS). Expression of epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Twist, and Snail, was assessed in a subset of the cohort. NM was observed in 94 cases (33.7%), of which ENE was observed in 32 cases (34%). NM with ENE was more frequently associated with tumors with poor differentiation than NM without ENE (P = .017). The 5-year OS and RFS rates of patients with NM and ENE was significantly worse (13.0% and 6.3%) than those with NM without ENE (37.7% and 21.4%) and those without NM (57.6% and 50.2%, respectively; P < .001). When pN category was matched, the OS and RFS was worse in patients with ENE than in those without ENE (P < .05). Moreover, the expression of E-cadherin and Twist was significantly different between NM areas with and without ENE (all, P < .001). Since ENE was associated with poorly differentiated ampullary adenocarcinomas and showed different expression of EMT markers, EMT could be a possible mechanism of ENE. Ampullary adenocarcinoma patients with ENE had worse OS and RFS than those without ENE. Therefore, evaluation of ENE can provide additional survival information for patients with surgically resected ampullary carcinoma.

Variations in antibiotic resistance genes and microbial community in sludges passing through biological nutrient removal and anaerobic digestion processes in municipal wastewater treatment plants.

Antimicrobial resistance (AMR) represents a relentless, silent pandemic. Contributing to this are wastewater treatment plants (WWTPs), a potential source of antibiotic resistance genes' (ARGs) transmission to the environment, threatening public health. The presence of ARGs in pathogenic bacteria and their release into the environment by WWTPs threatens the public health. The current study investigated changes in ARGs' abundance in biological nutrient removal (BNR) processes and anaerobic digestion (AD) reactors of two WWTPs. Also, microbial community structure, which is known to shape the distribution and abundance of ARGs, was also analyzed. The relative abundance of eight ARGs (tetX, tetA, tetM, TEM, sul1, sul2, ermB and qnrD) was quantified as ARGs' copies/16 S rRNA gene copies using quantitative polymerase chain reaction (qPCR). Microbial community composition was assessed by 16 S rRNA microbiome sequencing analysis. TetX was prevalent among the eight ARGs, followed by TEM and sul1. However, its abundance was decreased in the AD sludges compared to BNR sludges. Proteobacteria was the major bacterial phylum found in all the sludge samples, while Arcobacter, 12up and Acidovorax were the predominant genera. Acinetobacter and Flavobacterium were significantly more abundant in the BNR sludges, while 12up and Aeromonas were predominant in AD sludges. Principal component analysis (PCA) revealed a clear difference in dominant ARGs and bacteria between the sludges in the processes of BNR and AD of the two WWTPs. Clinically relevant bacterial genera, Klebsiella and Enterococcus, found in both the BNR and AD sludges, were significantly correlated with the tetX gene. Throughout this study, the relationship between microbial communities and specific ARGs was revealed, illustrating that the composition of the microbial community could play a vital role in the abundance of ARGs. These results will better inform future studies aimed at controlling the spread of ARGs and their potential hosts from WWTPs.

The T Category of Distal Extrahepatic Bile Duct Carcinoma: A Comparative Analysis With Invasive Tumor Thickness.

The T category of distal extrahepatic bile duct carcinoma (DBDC) is based on invasion depth from the basal lamina to the deepest infiltrating tumor cells. Recently, invasive tumor thickness (ITT) was proposed, defined as maximal vertical distance of invasive tumor components regardless of the basal lamina. We compared the predictive value of T category, and ITT grading in 424 surgically resected DBDCs. DBDCs were categorized as 6 Tis (1.4%), 134 T1 (<5 mm; 31.6%), 204 T2 (5 to 12 mm; 48.1%), and 80 T3 (>12 mm; 18.9%). With ITT, there were 6 G0 (no invasion; 1.4%), 3 G1 (<1 mm; 0.7%), 90 G2 (≥1 and <5 mm; 21.2%), 188 G3 (≥5 and <10 mm; 44.4%), and 137 G4 (≥10 mm; 32.3%). The 5-year survival rates of T1, T2, and T3 were 58.9%, 44.2%, and 18.2%, and those of ITT G1, G2, G3, and G4 were 33.3%, 54.1%, 51.6%, and 26.7%, respectively. The T category discriminated patient survival by overall (P<0.001) and pairwise (T1 vs. T2, P=0.007; T2 vs. T3, P<0.001) comparisons. ITT grading distinguished survival by overall and between G3-G4 (both P<0.001), with no survival differences observed between G1-G2 and G2-G3 comparisons. The T category more accurately discriminated patient survival than ITT grading. To determine the T category for DBDCs, (1) longitudinal sectioning on gross examination, especially for DBDCs with large papillary or nodular growth patterns; (2) evaluation of serial sections or alternative hematoxylin and eosin slides; (3) use of a straight or curved baseline depending on the shape of the peritumoral normal bile duct wall and/or the basal lamina of the peritumoral normal biliary epithelia/biliary intraepithelial neoplasias are recommended.

Granulocytic epithelial lesion (GEL) in heterotopic pancreas.

BACKGROUND: The diagnosis of type 2 autoimmune pancreatitis (AIP) is dependent on typical radiologic imaging and the presence of the granulocytic epithelial lesion (GEL), which is characterized by ductal neutrophilic infiltration with or without neutrophilic acinar infiltration. METHODS: We evaluated GEL and related clinicopathologic factors in 165 resected heterotopic pancreata (HPs) [57 gastric (35%), 56 duodenal (34%), 30 omental (18%), and 22 jejunal (13%)] and 29 matched orthotopic pancreata routinely examined during surgery. RESULTS: GEL was noted in 8% (13/165) of HPs, including ductal epithelial (6/13, 46%) and intraluminal (8/13, 62%) neutrophilic infiltrations. However, there was no GEL in orthotopic pancreata. Abdominal pain was observed in 6 (46%) patients with GEL-positive HPs. GEL was more commonly observed in HPs having symptoms (p = 0.029), a larger size (p = 0.028), and an infiltrative growth pattern (p = 0.006). In addition, periductal lymphoplasmacytic infiltration and fibrosis (both p < 0.001), interstitial fibrosis (p = 0.017), acinar neutrophilic infiltration (p = 0.032), venulitis (p = 0.050), acinar ductal metaplasia (ADM; p = 0.040), and pancreatic intraepithelial neoplasia/intraductal papillary mucinous neoplasms (PanIN/IPMN; p < 0.001) were more commonly seen in HPs with GEL than in those without GEL. Inflammatory bowel disease was present only in one patient with GEL-negative HP. CONCLUSIONS: GELs are detected in a subset of HPs without clinical evidence of AIP. Therefore, for the diagnosis of AIP, GEL should be carefully interpreted with the context of other histologic, clinical, and radiologic findings.

Relationships between presynaptic inhibition and static postural sway in subjects with and without diabetic neuropathy.

[Purpose] Diabetic peripheral neuropathy can often lead to balance impairment. The spinal reflex is a mechanism that is reportedly important for balance, but it has not been investigated in diabetic peripheral neuropathy patients. Moreover, inhibitory or facilitatory behavior of the spinal reflex-known as presynaptic inhibition-is essential for controlling postural sway. The purpose of this study was to compare the differences in as presynaptic inhibition and balance in subjects with and without diabetic peripheral neuropathy to determine the influence of presynaptic inhibition on balance in diabetic peripheral neuropathy patients. [Subjects and Methods] Presynaptic inhibition and postural sway were tested in eight patients (mean age, 58±6 years) and eight normal subjects (mean age, 59±7 years). The mean percent difference in conditioned reflex amplitude relative to the unconditioned reflex amplitude was assessed to calculate as presynaptic inhibition. The single-leg balance index was measured using a computerized balance-measuring device. [Results] The diabetic peripheral neuropathy group showed lower presynaptic inhibition (47±30% vs. 75±22%) and decreased balance (0.65±0.24 vs. 0.38±0.06) as compared with the normal group. No significant correlation was found between as presynaptic inhibition and balance score (R=0.37). [Conclusion] Although the decreased as presynaptic inhibition observed in diabetic peripheral neuropathy patients may suggest central nervous system involvement, further research is necessary to explore the role of presynaptic inhibition in decreased balance in diabetic peripheral neuropathy patients.

Assessment of the proximity between the mandibular third molar and inferior alveolar canal using preoperative 3D-CT to prevent inferior alveolar nerve damage.

BACKGROUND: The inferior alveolar nerve (IAN) may be injured during extraction of the mandibular third molar, causing severe postoperative complications. Many methods have been described for evaluating the relative position between the mandibular third molar and the inferior alveolar canal (IAC) on panoramic radiography and computed tomography, but conventional radiography provides limited information on the proximity of these two structures. The present study assessed the benefits of three-dimensional computed tomography (3D-CT) prior to surgical extraction of the mandibular third molar, to prevent IAN damage. METHODS: This retrospective study included 4917 extractions in 3555 patients who presented for extraction of the mandibular third molars. The cases were classified into three groups, according to anatomical relationship between the mandibular third molars and the IAC on panoramic radiography and whether 3D-CT was performed. Symptoms of IAN damage were assessed using the touch-recognition test. Data were compared using the chi-square test and Fisher's exact test. RESULTS: Among the 32 cases of IAN damage, 6 cases were included in group I (0.35 %, n = 1735 cases), 23 cases in group II (1.1 %, n = 2063 cases), and 3 cases in group III (0.27 %, n = 1119 cases). The chi-square test showed a significant difference in the incidence of IAN damage between groups I and II. No significant difference was observed between groups I and III using Fisher's exact test. In the 6 cases of IAN damage in group I, the mandibular third molar roots were located lingual relative to the IAC in 3 cases and middle relative to the IAC in 3 cases. The overlap was ≥2 mm in 3 of 6 cases and 0-2 mm in the remaining 3 cases. The mean distance between the mandibular third molar and IAC was 2.2 mm, the maximum distance 12 mm, and the minimum distance 0.5 mm. Greater than 80 % recovery was observed in 15 of 32 (46.8 %) cases of IAN damage. CONCLUSIONS: 3D-CT may be a useful tool for assessing the three-dimensional anatomical relationship and proximity between the mandibular third molar and IAC in order to prevent IAN damage during extraction of mandibular third molars.

A thiazolothiazole based Cu2+ selective colorimetric and fluorescent sensor via unique radical formation.

A novel thiazolothiazole-based Cu(2+) colorimetric and fluorescent sensor is reported. A highly selective colorimetric change from yellow to dark green was observed among various metal ions after adding Cu(2+). Unique radical formation can engender these highly selective colorimetric and fluorescent changes.

A new fluorescein derivative bearing a boronic acid group as a fluorescent chemosensor for fluoride ion.

A new fluorescein derivative 1 bearing a boronic acid group was investigated as a fluorescent chemosensor for F-. An off-on type fluorescence enhancement was observed by the blocking of the photoinduced electron transfer mechanism, which was induced by the interaction between fluoride and boronic acid moiety.