Hepatocellular carcinoma in a transplanted donor liver and colon cancer developing in a patient with a complex background: A case report.

The development of tumors in livers transplanted from hepatitis B virus (HBV)-negative donors to patients with hepatitis B and cirrhosis is rare. The present study describes the case of a woman in her 60s who developed hepatocellular carcinoma (HCC) in her grafted liver, 19 years after transplantation, as well as a metachronous colorectal tumor. The pathological findings, including clinical, immunohistochemical and molecular results, are described in the present case report. The liver tumor was a conventional HCC and the colorectal tumor comprised a tubular adenocarcinoma. Immunohistochemistry of both tumors showed a loss of expression of mutL homolog 1 and postmeiotic segregation increased 2 in the tumor cells, confirming microsatellite instability-high (MSI-H) status. Furthermore, a molecular study detected the presence of genes located on the Y chromosome in the normal and tumor tissues of the liver, proving that the HCC occurred in the grafted liver. The present report also discusses that prolonged use of immunosuppressive drugs to prevent post-transplant rejection, poorly controlled diabetes mellitus and MSI-H may have contributed to the risk of tumor development.

Giant retroperitoneal myolipoma mimicking liposarcoma: report of a resected case and review of the literature.

Myolipomas are rare tumors that are often difficult to differentiate from liposarcoma. Herein, we report a case of resected giant myolipoma preoperatively diagnosed as liposarcoma. A 63-year-old woman was suspected of having a large retroperitoneal liposarcoma on October 202X. The patient was referred to our department for tumor resection and a histological diagnosis. After consultation with the urology, obstetric and gynecology, and vascular surgery departments, tumor resection was planned, including the potential resection of other organs. Intraoperative findings revealed a large, elastic, soft tumor with a smooth surface and a capsule occupying the entire abdominal cavity. The tumor was adherent to the stomach, left colon, and uterine adnexa, and no invasion was observed. The tumor was completely resected, and organ resection was not necessary. The tumor was 40 cm in diameter and 4.0 kg in weight. Pathological examination and immunostaining confirmed a diagnosis of myolipoma. The patient's postoperative course was uneventful, and she was discharged on postoperative day 10 with no complications. Twelve months after surgery, the patient was doing well. To the best of our knowledge, we report a complete resection of the largest retroperitoneal myolipoma reported to date. Physicians should consider surgery, even for suspected large sarcomas that may be difficult to resect completely.

Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1.

SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (VH T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2.

Evaluating staging laparoscopy indications for pancreatic cancer based on resectability classification and treatment strategies for patients with positive peritoneal washing cytology.

Introduction: The prognosis of pancreatic ductal adenocarcinoma (PDAC) in patients with positive peritoneal washing cytology (CY1) is poor. We aimed to evaluate the results of staging laparoscopy (SL) and treatment efficacy in CY1 patients based on a resectability classification. Methods: We retrospectively reviewed 250 patients with PDAC who underwent SL before the initial treatment between 2017 and 2023 at the University of Toyama. Results: The breakdown of cases by resectability classification was resectable (R):borderline resectable (BR):unresectable locally advanced (UR-LA) = 131:48:71 cases. The frequency of CY1 increased in proportion to the degree of local progression (R:BR:UR-LA = 20:23:34%), but the frequencies of liver metastasis or peritoneal dissemination were comparable (R:BR:UR-LA = 6.9:6.3:8.5%). Most CY1 patients received gemcitabine along with nab-paclitaxel therapy. The CY-negative conversion rates (R:BR:UR-LA = 70:64:52%) and conversion surgery rates (R:BR:UR-LA = 40:27:9%) were inversely proportional to the degree of local progression.Comparing H0P0CY1 factors for each classification, patients with H0P0CY1 had significantly more pancreatic body or tail carcinoma and tumor size ≥32 mm in R patients, whereas in BR patients, duke pancreatic monoclonal antigen type 2 (DUPAN-2) ≥ 230 U/mL was a significant factor. In contrast, no significant factors were observed in UR-LA patients. Conclusion: The CY1 rates, CY-negative conversion rates, and conversion surgery rates varied according to local progression. In the case of R and BR, SL could be considered in patients with pancreatic body or tail carcinoma, large tumor size, or high DUPAN-2 level. In UR-LA, SL might be considered for all patients.

Pembrolizumab-induced Acute Tubulointerstitial Nephritis Accompanying Fanconi Syndrome and Type 1 Renal Tubular Acidosis.

Pembrolizumab, an immune checkpoint inhibitor, is used to treat a variety of refractory malignancies. However, these agents are sometimes associated with immune-related adverse events. A 71-year-old woman received pembrolizumab-integrated chemotherapy to treat her recurrent mandibular gingival cancer. Five months after stopping pembrolizumab, she developed acute tubulointerstitial nephritis associated with Fanconi syndrome and type 1 renal tubular acidosis, which resolved with steroid therapy. We experienced a case of pembrolizumab-induced Fanconi syndrome and type 1 renal acidosis. We recommend follow-up of the tubular function in addition to the renal function even after discontinuation of pembrolizumab.

A Case Report of Anti-TIF1-γAntibody-Positive Dermatomyositis Concomitant with Small Cell Neuroendocrine Carcinoma of the Urinary Bladder.

Small cell neuroendocrine carcinoma is rare among urinary bladder cancer types, and to date, there are no case reports of concurrent antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis. We describe the case of a 69-year-old Japanese man who presented with elevated creatine kinase levels and haematuria on medical examination. Approximately one month later, he developed dysphagia. Laryngoscopy confirmed laryngeal dysfunction. He also presented with muscle weakness and a skin rash. Magnetic resonance imaging of the upper extremities suggested bilateral brachial muscle myositis. He was diagnosed as having dermatomyositis and was later found to be positive for antitranscriptional intermediary factor 1-γ antibody. Computed tomography revealed an intravesical space-occupying lesion and right iliac lymphadenopathy, suggesting urinary bladder cancer. The patient was admitted to our hospital for treatment. Urinary bladder biopsy confirmed small cell neuroendocrine carcinoma because tumour cells were positive for synaptophysin, CD56, and chromogranin A. Thus, the patient was diagnosed as having an antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis concomitant with urinary bladder small cell neuroendocrine carcinoma. The patient was treated with glucocorticoid and intravenous immune globulin therapy for dermatomyositis. Radiotherapy was selected for the carcinoma. Although muscle weakness and skin symptoms improved with treatment, dysphagia persisted. Furthermore, expression of the transcriptional intermediary factor 1-γ protein in tumour cells was also confirmed by immunohistochemistry, but the significance is unknown. It should be noted that antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis can occur concomitantly with such a rare malignancy.

Prediction of visceral pleural invasion of clinical stage I lung adenocarcinoma using thoracoscopic images and deep learning.

PURPOSE: To develop deep learning models using thoracoscopic images to identify visceral pleural invasion (VPI) in patients with clinical stage I lung adenocarcinoma, and to verify if these models can be applied clinically. METHODS: Two deep learning models, one based on a convolutional neural network (CNN) and the other based on a vision transformer (ViT), were applied and trained via 463 images (VPI negative: 269 images, VPI positive: 194 images) captured from surgical videos of 81 patients. Model performances were validated via an independent test dataset containing 46 images (VPI negative: 28 images, VPI positive: 18 images) from 46 test patients. RESULTS: The areas under the receiver operating characteristic curves of the CNN-based and ViT-based models were 0.77 and 0.84 (p = 0.304), respectively. The accuracy, sensitivity, specificity, and positive and negative predictive values were 73.91, 83.33, 67.86, 62.50, and 86.36% for the CNN-based model and 78.26, 77.78, 78.57, 70.00, and 84.62% for the ViT-based model, respectively. These models' diagnostic abilities were comparable to those of board-certified thoracic surgeons and tended to be superior to those of non-board-certified thoracic surgeons. CONCLUSION: The deep learning model systems can be utilized in clinical applications via data expansion.

Isoxanthohumol improves obesity and glucose metabolism via inhibiting intestinal lipid absorption with a bloom of Akkermansia muciniphila in mice.

OBJECTIVE: Polyphenols have health-promoting effects, such as improving insulin resistance. Isoxanthohumol (IX), a prenylated flavonoid found in beer hops, has been suggested to reduce obesity and insulin resistance; however, the mechanism remains unknown. METHODS: High-fat diet-fed mice were administered IX. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice. RESULTS: The administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration increased markers of intestinal barrier function, including thickening the mucin layer and increasing caludin-1, a tight-junction related protein in the colon. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of Akkermansia muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A. muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A. muciniphila on lipid and glucose metabolism, we monocolonized either A. muciniphila or Bacteroides thetaiotaomicron to GF mice. A. muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis. CONCLUSIONS: Our study demonstrated that IX prevents obesity and enhances glucose metabolism by inhibiting dietary fat absorption. This mechanism is linked to suppressing pancreatic lipase activity and shifts in microbial composition, notably an increase in A. muciniphila. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.

Efficacy of staging laparoscopy for resectable pancreatic cancer on imaging and the therapeutic effect of systemic chemotherapy for positive peritoneal cytology.

BACKGROUND: The frequency and prognosis of positive peritoneal washing cytology (CY1) in resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. The objective of this study was to identify the clinical implications of CY1 in R-PDAC and staging laparoscopy (SL). METHODS: We retrospectively analyzed 115 consecutive patients with R-PDAC who underwent SL between 2018 and 2022. Patients with negative cytology (CY0) received radical surgery after neoadjuvant chemotherapy, while CY1 patients received systemic chemotherapy and were continuously evaluated for cytology. RESULTS: Of the 115 patients, 84 had no distant metastatic factors, 22 had only CY1, and nine had distant metastasis. Multivariate logistic regression revealed that larger tumor size was an independent predictor of the presence of any distant metastatic factor (OR: 6.30, p = .002). Patients with CY1 showed a significantly better prognosis than patients with distant metastasis (MST: 24.6 vs. 18.9 months, p = .040). A total of 11 CY1 patients were successfully converted to CY-negative, and seven underwent conversion surgery. There was no significant difference in overall survival between patients with CY0 and those converted to CY-negative. CONCLUSION: SL is effective even for R-PDAC. The prognosis of CY1 patients converted to CY-negative is expected to be similar to that of CY0 patients.

A case of squamous cell carcinoma of the breast achieved a pathological complete response after dose-dense AC + dose-dense PTX.

BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare form of breast cancer, accounting for approximately 0.1% of all breast cancers. It is known for its rapid tumor growth and poor prognosis with no established treatment. CASE PRESENTATION: A 56-year-old woman was diagnosed with breast SCC with axillary, supraclavicular and internal thoracic lymph node metastases. She received neoadjuvant chemotherapy (NAC) with dose-dense doxorubicin and cyclophosphamide (AC) followed by dose-dense paclitaxel (PTX). This treatment resulted in a pathological complete response (pCR) after breast-conserving surgery. The patient was then treated with radiotherapy. She remained free of recurrence for three years postoperatively. CONCLUSIONS: We report a rare case of breast SCC treated with preoperative dose-dense chemotherapy, resulting in pCR and allowing breast-conserving surgery.

Prognostic Impact of Margin Status in Distal Cholangiocarcinoma.

BACKGROUND: A positive ductal margin is strongly associated with poor survival in patients with distal cholangiocarcinoma. However, the significance of the radial margin status and its effect on survival are not fully clarified. METHODS: All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between January 2000 and December 2018 at Tokai University Hospital were retrospectively analyzed. Positive margins were divided into positive ductal margin and positive radial margin. RESULTS: One hundred and eight consecutive patients with distal cholangiocarcinoma underwent pancreatoduodenectomy. Margin-negative R0 resection was performed in 85 patients (79%). Twenty-three patients (21%) had a positive resection margin (R1 resection). The 5-year survival rate and median overall survival for patients with R0 resection and those with R1 resection was 64%, 98 months and 25%, 26 months, respectively. There was a significant difference in survival between patients with R0 resection and those with R1 resection (p < 0.001). Patients with positive radial margin (n = 10) had a significantly worse outcome than those with positive ductal margin (n = 13) (p = 0.016). Univariate analysis showed that R1 resection, lymph node metastasis, tumor depth, portal vein invasion, pancreatic invasion, lymphatic invasion, and venous invasion were significant prognostic factors. Multivariate analysis confirmed that R1 resection and nodal involvement were significant independent prognostic indicators after surgical resection for distal cholangiocarcinoma. CONCLUSIONS: Positive surgical margin and nodal involvement were the strongest predictors of poor survival in patients with distal cholangiocarcinoma. Patients with a positive radial margin had a significantly worse outcome than those with a positive ductal margin.

Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP7 metabolism in the enteric nervous system.

Inositol pyrophosphates regulate diverse physiological processes; to better understand their functional roles, assessing their tissue-specific distribution is important. Here, we profiled inositol pyrophosphate levels in mammalian organs using an originally designed liquid chromatography-mass spectrometry (LC-MS) protocol and discovered that the gastrointestinal tract (GIT) contained the highest levels of diphosphoinositol pentakisphosphate (IP7) and its precursor inositol hexakisphosphate (IP6). Although their absolute levels in the GIT are diet dependent, elevated IP7 metabolism still exists under dietary regimens devoid of exogenous IP7. Of the major GIT cells, enteric neurons selectively express the IP7-synthesizing enzyme IP6K2. We found that IP6K2-knockout mice exhibited significantly impaired IP7 metabolism in the various organs including the proximal GIT. In addition, our LC-MS analysis displayed that genetic ablation of IP6K2 significantly impaired IP7 metabolism in the gut and duodenal muscularis externa containing myenteric plexus. Whole transcriptome analysis of duodenal muscularis externa further suggested that IP6K2 inhibition significantly altered expression levels of the gene sets associated with mature neurons, neural progenitor/stem cells, and glial cells, as well as of certain genes modulating neuronal differentiation and functioning, implying critical roles of the IP6K2-IP7 axis in developmental and functional regulation of the enteric nervous system. These results collectively reveal an unexpected role of mammalian IP7-a highly active IP6K2-IP7 pathway is conducive to the enteric nervous system.

Prognostic Impact of Positive Peritoneal Lavage Cytology on Resectable Pancreatic Body and Tail Cancer: A Retrospective Study.

BACKGROUND: The prognostic impact of positive peritoneal lavage cytology on pancreatic cancer is unclear. Therefore, this study aimed to evaluate its impact in resectable pancreatic body and tail cancer. METHODS: Between January 2006 and December 2019, 97 patients with pancreatic body and tail cancer underwent peritoneal lavage cytology and curative resection at our institution. We analyzed the impact of positive peritoneal lavage cytology on clinicopathological factors and on the prognosis of pancreatic body and tail cancer. RESULTS: Malignant cells were detected in 14 patients (14.4%) using peritoneal lavage cytology. In these patients, the tumor diameter was significantly larger (p < 0.001) and anterior serosal invasion (p = 0.034), splenic artery invasion (p = 0.013), lympho-vessel invasion (p = 0.025), and perineural invasion (p = 0.008) were significantly more frequent. The R1 resection rate was also significantly higher in patients with positive peritoneal lavage cytology than in negative patients (p = 0.015). Positive peritoneal lavage cytology had a significantly poor impact on overall survival (p = 0.001) and recurrence-free survival (p < 0.001). This cytology was also an independent poor prognostic factor for recurrence (p = 0.022) and was associated with peritoneal dissemination and liver metastasis. CONCLUSIONS: Positive peritoneal lavage cytology is considered to be indicative of more systemic disease in patients with resectable pancreatic body and tail cancer than in patients with negative peritoneal lavage cytology. Early detection of pancreatic cancer before it develops micrometastases is important to improve prognosis, and CY+ patients require more intensive multimodality treatment than standard treatment for resectable pancreatic cancer.

miR-4653-3p overexpression is associated with a poor prognosis of pancreatic ductal adenocarcinoma via HIPK2 downregulation.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant tumor. Several upregulated and downregulated microRNAs (miRNAs) are associated with invasiveness, tumorigenesis, and prognosis of PDAC. Herein, using in situ hybridization, we evaluated miR-4653-3p expression and pancreatic intraepithelial neoplasia (PanIN) and the association between miR-4653-3p expression and clinicopathological factors in PDAC patients. The miR-4653-3p target was also identified. Ninety PDAC cases, including 30 each with normal pancreatic ducts, low-grade PanINs, and high-grade PanINs, were evaluated. miR-4653-3p expression increased in the order-normal pancreatic duct, low-grade PanIN, high-grade PanIN, and PDAC-with no expression detected in normal pancreatic duct. High expression significantly correlated with advanced pathological T stage, lymph node metastasis, advanced Union for International Cancer Control stage, perineural invasion, venous involvement, and shorter overall and disease-specific survival. Homeodomain Interacting Protein Kinase 2 (HIPK2) was identified as a miR-4653-3p target based on mRNA microarray analysis and database screening. In MIA PaCa-2 cells, miR-4653-3p significantly downregulated HIPK2 expression. HIPK2 expression, unlike that of miR-4653-3p, decreased in the order-normal pancreatic duct, low-grade PanIN, high-grade PanIN, and PDAC. Low HIPK2 expression was associated with shorter overall and disease-specific survival in PDAC patients. Thus, miR-4653-3p associates with tumorigenesis and worse prognosis, partly by reducing HIPK2 expression.

Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems.

Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreatobiliary system are tumors comprising oncocytic cells, in which three types of fusion genes involving -PRKACA/-PRKACB were recently identified. IOPNs infrequently combine with other histological subtypes of pancreatic intraductal papillary mucinous neoplasms (IPMNs) and intraductal papillary neoplasms of the bile duct (IPNBs). This study aimed to confirm the sensitivity/specificity of the fusion genes for IOPNs and to examine their significance in other oncocytic lesions. An RT-PCR, followed by DNA sequencing, was undertaken to examine the fusions in 18 histologically diagnosed IOPNs, including four combined IOPNs. Moreover, in two IOPN cases, invasive carcinomatous lesions were separately examined on their fusion status. Oncocytic thyroidal (n = 10), renal (n = 10), and salivary gland (n = 3) lesions and IPMNs (n = 9)/IPNBs (n = 4) with focal oncocytic changes were examined as controls. Fluorescence in situ hybridization using PRKACA break-apart probes was conducted for the combined IOPN cases. Target sequencing of KRAS exon2/3 and GNAS exon 8/9 was performed for IOPN cases. Fusions were detected in all IOPN cases including invasive lesions/none of the control cases. The fusion event was confirmed also in non-IOPN component in one of the four combined cases. Regarding mutation events, 5.6%/0% of IOPNs were KRAS-mt/GNAS-mt, respectively, and both components of combined IOPNs were all KRAS-wt/GNAS-wt. In conclusion, our study confirmed the sensitivity and specificity of these fusions for IOPNs. Here, we analyzed the roles of these fusion genes in combined IOPNs, proposing the possibility of IOPN development via IPMNs/IPNBs. Further studies with more combined cases are warranted.

Background features in the cytology of pancreatic neoplasms.

Cytology is a useful method for diagnosing pancreatic neoplasms. Although endoscopic ultrasound-guided fine-needle aspiration has recently become the mainstream method for the diagnosis of pancreatic neoplasms, pancreatic juice and pancreatic duct brushing cytology continue to be useful diagnostic methods for the investigation of pancreatic neoplasms. Diagnoses using pancreatic cytology are primarily based on the features related to tumor cells; however, evaluation of the background features provides important information that could further aid the diagnosis. Pancreatic neoplasms show various histological types, each of which is associated with its own characteristic background features. The necrotic background, desmoplastic stroma, and presence of cancer-associated fibroblasts are background features of pancreatic ductal adenocarcinoma, a mucinous background is associated with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, and hyaline globules are observed in solid pseudopapillary neoplasms. However, some background features are associated with more than one histological type of pancreatic neoplasm, highlighting the importance to base a diagnosis on the results of a comprehensive analysis of not only the background features but also the tumor cells. Here, we provide a review of the key background cytological features of pancreatic neoplasms, which can serve as a guide to improve diagnosis and research.

Isolated trochlea osteochondral fracture of the distal humerus in a 6-year-old patient surgically fixed using biodegradable pins: A case study with over 3 years of follow-up.

Isolated humeral trochlea fracture, particularly in skeletally immature children, is extremely rare. The exact mechanism of this injury remains unknown because the humeral trochlea is embraced within the olecranon fossa without any muscular or ligamentous attachment. We report the treatment of a 6-year-old boy who sustained an isolated trochlea osteochondral fracture when he fell with his elbow in a flexed position while skateboarding. The patient had a history of lateral condyle fracture of the ipsilateral humerus one year previously. At the diagnosis, computed tomography (CT) revealed a small bony fragment displaced anteromedially from the superior border of the trochlea with lifting of its lateral border. Ultrasonography confirmed instability of the fractured segment. At the time of surgery, the anterior trochlea surface fracture formed a hinged fracture line on its proximal and medial border. The fracture was anatomically reduced and fixed using biodegradable pins. Postoperatively, the involved elbow showed a sufficient functional recovery to a normal level without complications during 3 years of observation, although the biodegradable pins remained radiographically in place with partial degradation. The laterally opened avulsed fragment on primary CT clearly depicted the mechanism of injury: the impact entered from the lateral side of the elbow and progressed from the longitudinal ridge of the coronoid process onto the sulcus of the trochlea to shear off the anteromedial portion of the trochlea in a medial direction. The use of biodegradable pins for fixing a trochlea fracture in a skeletally immature patient provided favorable fracture healing; however, close observation is necessary until the completion of skeletal growth because of the lack of sufficient information on the long-term prognosis of trochlea fracture, especially when treated using biodegradable implants.

DNMT1 Expression and DNA Methylation in Intraductal Papillary Neoplasms of the Bile Duct.

BACKGROUND/AIM: Intraductal papillary neoplasms of the bile duct (IPNB) are histologically and clinically classified as type 1 and 2. This study aimed to identify the differences between these two types. MATERIALS AND METHODS: Based on multiple gene expression analysis (MGEA) using type 1, type 2, and pancreatic intraductal papillary mucinous neoplasms (n=4, 6, and 5, respectively), immunohistochemistry of DNMT1 and methylation-specific PCR for p16, APC, BRCA1, hMLH1, TIMP3, and SOX17 were performed on type 1 and 2 IPNBs (n=14, each). RESULTS: The DNMT1 protein was highly expressed (p<0.001) in 28.6% of type 1 cases and all type 2 cases. The DNA methylation ratio for the six genes in total as well as for SOX17 was lower in type 1 than in type 2 (p<0.05 each). CONCLUSION: Type 2 IPNB showed increased DNMT1 protein expression and increased DNA methylation frequency of the examined tumor suppressor genes compared to type 1. DNMT1 IHC may be helpful in discriminating between these two types.

Diagnostic Categories and Key Features for Pathological Diagnosis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Samples of Pancreatic Lesions: A Consensus Study.

OBJECTIVES: This study aimed to establish a reliable and reproducible categorized diagnostic classification system with identification of key features to achieve accurate pathological diagnosis of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) samples of pancreatic lesions. METHODS: Twelve pathologists examined virtual whole-slide images of EUS-FNAB samples obtained from 80 patients according to proposed diagnostic categories and key features for diagnosis. Fleiss κ was used to assess the concordance. RESULTS: A hierarchical diagnostic system consisting of the following 6 diagnostic categories was proposed: inadequate, nonneoplasm, indeterminate, ductal carcinoma, nonductal neoplasm, and unclassified neoplasm. Adopting these categories, the average κ value of participants was 0.677 (substantial agreement). Among these categories, ductal carcinoma and nonductal neoplasm showed high κ values of 0.866 and 0.837, respectively, which indicated the almost perfect agreement. Key features identified for diagnosing ductal carcinoma were necrosis in low-power appearance; structural atypia/abnormalities recognized by irregular glandular contours, including cribriform and nonuniform shapes; cellular atypia, including enlarged nuclei, irregular nuclear contours, and foamy gland changes; and haphazard glandular arrangement and stromal desmoplasia. CONCLUSIONS: The proposed hierarchical diagnostic classification system was proved to be useful for achieving reliable and reproducible diagnosis of EUS-FNAB specimens of pancreatic lesions based on evaluated histological features.