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Abstract Background The effectiveness of peer learning has been recognized and discussed by many scholars, and implemented in the formal curriculums of medical schools internationally. However, there is a general dearth of studies in measuring the objective outcomes in learning. Methods We investigated the objective effect of near-peer learning on tutee’s emotions and its equivalence within the formal curriculum of a clinical reasoning Problem Based Learning session in a Japanese medical school. Fourth-year medical students were assigned to the group tutored by 6th-year students or by faculties. The positive activating emotion, positive deactivating emotion, negative activating emotion, negative deactivating emotion, Neutral emotion were measured using the Japanese version of the Medical Emotion Scale (J-MES), and self-efficacy scores were also assessed. We calculated the mean differences of these variables between the faculty and the peer tutor groups and were statistically analyzed the equivalence of these scores. The equivalence margin was defined as a score of 0.4 for J-MES and 10.0 for the self-efficacy score, respectively. Results Of the 143 eligible participant students, 90 were allocated to the peer tutor group and 53 were allocated to the faculty group. There was no significant difference between the groups. The 95% confidence interval of the mean score difference for positive activating emotions (–0.22 to 0.15), positive deactivating emotions (–0.35 to 0.18), negative activating emotions (–0.20 to 0.22), negative deactivating emotions (–0.20 to 0.23), and self-efficacy (–6.83 to 5.04) were withing the predetermined equivalence margins for emotion scores, meaning that equivalence was confirmed for these variables. Conclusions Emotional outcomes were equivalent between near-peer PBL sessions and faculty-led sessions. This comparative measurement of the emotional outcomes in near-peer learning contributes to understanding PBL in the field of medical education.

BackgroundMultiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple epithelial neuroendocrine tumors (NETs) and non-NETs in various organs. MEN1 encodes a 610-amino acid-long tumor suppressor protein, menin. The optimal treatment for multiple tumors, identification of the most critical tumors for patient prognosis, and menin immunohistochemistry findings remain controversial. Therefore, we aimed to elucidate these issues through a histological analysis of tumors and tumor-like lesions in a Japanese family, comprising a father and his two sons, who had MEN1 with Zollinger–Ellison syndrome (ZES).Patients and methodsAll family members had a germline alteration in exon 10, c.1714-1715 del TC of MEN1, and exhibited multiple synchronous and metachronous tumors. The patients had pulmonary NETs, hyperparathyroidism, hypergastrinemia, pituitary adenomas, pancreaticoduodenal NETs, adrenocortical adenoma with myelolipoma, nodular goiter of the thyroid, lipomas, and angiofibroma. Most tumors were resected and histologically examined. We compared their clinical courses and tumor histology, and conducted menin immunohistochemistry (IHC).ResultsTwo patients died of pulmonary NET G2. One patient who underwent pancreaticoduodenectomy was cured of ZES; however, the two other patients who did not undergo pancreaticoduodenectomy suffered persistent ZES despite treatment with octreotide. Menin IHC revealed varying NET intensities, ranging from positive to negative stains.ConclusionPancreaticoduodenectomy is the most effective treatment for ZES. Long-term follow-up is essential for pulmonary NET G2 owing to the risk of distant metastasis and/or multiplicity. Moreover, the variability of menin IHC in MEN1-related tumors may indicate the pattern of tumor formation rather than the diagnostic utility of menin in MEN1.

Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.

Abstract Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P

Abstract Background Intra-ampullary papillary-tubular neoplasm (IAPN) has been classified as a Vater papillary tumor. The prognosis of IAPN is generally relatively good. Here, we describe a patient with a mucinous adenocarcinoma cluster in the Vater papilla of IAPN origin. Clinical presentation The patient was a 66-year-old man who was admitted to our hospital after a diagnosis of pancreatic head carcinoma based on a pancreatic duct dilatation found on abdominal ultrasound. CT showed a 40 mm lesion in the pancreatic head and expansion of the main pancreatic duct to a maximum diameter of 9 mm on the caudal side of the lesion. The extrahepatic bile duct had also expanded to a maximum diameter of 8 mm. PET/CT showed fluorodeoxyglucose (FDG) accumulation of SUVmax 6.02 that corresponded to the tumor in the pancreatic head, though it did not suggest distant metastasis. The patient was diagnosed with pancreatic head carcinoma T3 N0 M0 Stage IIA and underwent a pancreaticoduodenectomy. Pathology indicated that the tumor in the pancreatic head was a benign inflammatory lesion. On the other hand, the papillotubular tumor pervading the lumen in the duodenal papillary common channel met the criteria for IAPN, and a mucinous adenocarcinoma cluster found in the surrounding stroma suggested malignant transformation of IAPN. No metastasis to lymph nodes was demonstrated. With regard to the mucus phenotype of each lesion, the IAPN was MUC2 and MUC5AC positive, while the mucinous adenocarcinoma was MUC2-positive and MUC5AC-negative. In addition, CD10 was negative in both lesions, suggesting that mucus transformation from the gastric type to the intestinal type was a key element. A blood test 10 months after surgery showed increased CA19-9 (105 U/mL) and CEA (7.1 ng/mL). Abdominal CT showed multiple cystoid nodes in the liver, which were diagnosed as multiple liver metastases of mucinous adenocarcinoma transformed from the IAPN. Conclusions We reported a case with IAPN that developed in the Vater papilla, which took an extremely malignant course. IAPN generally has a good prognosis, but it is important to understand that a malignant course may occur.

The COVID-19 pandemic has greatly changed medical education, and medical trainees’ self-regulation has become more emphasized. In Japan, the concept of self-regulated learning has not been fully applied in health profession education due to a lack of effective measurement tools. We aimed to validate the translated Japanese version of the Motivated Strategies for Learning Questionnaire in the context of Problem-Based Learning (J-MSLQ-PBL). The questionnaire employs a seven-point Likert-type scale with 81 items and is categorized into two sections: motivation and learning strategies. An exploratory factor analysis (EFA) was conducted by using Promax rotation to examine the factor structure of the scale, using the collected data from 112 Japanese medical students. Factor extraction was based on a scree plot investigation, and an item was accepted when the factor loading was ≥0.40. In the motivation section, the extracted factors from the EFA were well aligned with the subscales of the original MSLQ, including “Self-Efficacy for Learning and Performance”, “Task Value”, “Self-Efficacy for Learning and Performance”, “Test Anxiety”, “Extrinsic Goal Orientation”, and “Intrinsic Goal Orientation”. In the learning strategies, the extracted factors poorly matched the structure of the original subscales. This discrepancy could be explained by insufficient translation, the limited sample size from a single medical school, or cross-cultural differences in learning strategies between Western and Japanese medical students. Only the motivation part of the J-MSLQ-PBL should be implemented to measure the competency elements of self-regulated learning in Japan.

Objectives Mucin phenotype is a tool to classify gastric cancer, but the relationship between mucin phenotype and its malignancy is still controversial. This study aimed to clarify the relationship between mucin phenotype and the malignant potential of gastric cancer. Methods A total of 82 cases of early-stage differentiated adenocarcinoma (submucosal invasion cases) obtained from surgeries were studied by immunohistochemistry. Gastric mucin phenotype and E-cadherin expression were analyzed in the mucosal and submucosal layer. E-cadherin expression was analyzed by using imaging software (ImageJ) for objective data analysis. Furthermore, the mucin phenotypic shift was analyzed from mucosa to submucosa. Results We found that: (1) tumors with intestinal mucin phenotype had statistically more venous invasion in the submucosal lesion; (2) tumors with an intestinal phenotype that showed venous invasion in the submucosal lesion had a higher percentage of tumors that showed loss of phenotype; (3) no dominant change in E-cadherin expression was observed from the mucosa to submucosa. Conclusion Tumors with loss of phenotype and submucosal intestinal phenotype showed predominantly more venous invasion, so examining the identification of phenotypes and phenotype shifts can be expected to be a factor that influences treatment strategies after endoscopic treatment or after surgical resection.

Abstract Background The malignant transformation of an ectopic pancreas in the duodenum is extremely rare. Herein, we report a case of an adenocarcinoma that arose from an ectopic pancreas. We also reviewed 14 cases of malignant transformations arising from an ectopic pancreas in the duodenum that were previously published. Case presentation An 81-year-old man with a 1-month history of vomiting was admitted to our institution. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) scans revealed an obstruction at the first part of the duodenum. A distal gastrectomy was performed for diagnostic and therapeutic purposes. The histopathological examination of the resected specimen showed adenocarcinoma that arose from an ectopic pancreas (Heinrich type 1). The patient is alive without relapse at 18 months of follow-up. Conclusions Adenocarcinoma that arises from an ectopic pancreas should be considered when an obstruction is identified in the duodenum.

Abstract Background Calcifying nested stromal epithelial tumor (CNSET) is a primary neoplasm of the liver, characterized by well-demarcated nests consisting of spindle and epithelioid cells with calcification and bone formation. An association of Cushing syndrome with CNSET has drawn attention, but the origin of CNSET has not been clarified. Case presentation We report here the case of a 20-year-old male with Klinefelter syndrome who underwent liver resection for an increasing liver tumor that was pathologically diagnosed with CNSET. He was postoperatively followed up and received several examinations, and recurrences and extrahepatic lymph node metastases were detected on the 64th day after surgery. Chemoembolization and chemotherapy were not effective, leading to tumor progression with development of progressive liver failure, and the patient finally died 164 days after hepatectomy. Conclusions This case suggests that an imbalance of hormones affects the genesis and progression of CNSET, and indicates the importance of closely following patients with CNSET by imaging with attention to hepatic recurrence and extrahepatic metastases.

Extrahepatic bile duct carcinoma is a potentially malignant gastrointestinal lesion. Cancer cells spread via the lymphatic system to regional lymph nodes and help in tumor progression. However, there are no reports on the prognostic impact of extracapsular lymph node invasion and myofibroblastic activity in this cancer. Hence, we classified the histopathologic patterns of lymph nodes into 2 patterns: extracapsular lymph node invasion or not. Based on this, we investigated 32 cases of extrahepatic bile duct cancer with lymph node metastasis and classified 21 cases as positive and 11 cases as negative. The extracapsular lymph node invasion cases were associated with poor disease-free survival and overall survival. The myofibroblast density of the metastatic foci was significantly higher in the extracapsular lymph node invasion cases. This is the first study to demonstrate that extracapsular lymph node invasion cases were associated with poor prognosis and that the myofibroblast distribution contributed to malignancy.

We report a case of a 66-year-old woman who developed hyperparathyroidism due to a large intrathyroid parathyroid adenoma with episodes of acute pancreatitis. She had previously been treated for acute pancreatitis twice. Serum calcium was 12.4 mg/dL, and intact parathyroid hormone was 253 pg/dL. Ultrasonography and computed tomography of the neck with contrast enhancement revealed a soft tissue mass (28 mm transverse diameter) within the left lobe of the thyroid. 99mTc-MIBI scintigraphy demonstrated focal accumulation due to increased radiotracer uptake in the left thyroid lobe. Left hemithyroidectomy was performed. Histopathology showed no signs of invasion, and this is consistent with parathyroid adenoma. Immunostaining was positive for expression of chromogranin A and parathyroid hormone. The patient had no episode of pancreatitis after the operation. In a patient with recurrent episodes of pancreatitis, the possibility of complication with hyperparathyroidism should be considered.

With the prolongation of the mean lifespan, the number of elderly individuals undergoing liver resection for colorectal cancer liver metastasis (CRLM) following chemotherapy has increased. However, the effect of age on the development of chemotherapy-associated liver injury (CALI) in CRLM remains unclear. The aim of the present study was to elucidate the effect of age on the development of CALI in CRLM. A total of 64 patients undergoing liver resection for CRLM following oxaliplatin-based chemotherapy (OBC) were investigated. The patients were divided into three groups (group A: <65 years, group B: 65-74 years and group C: >75 years) according to age at surgery, and the development rate of CALI was compared between the groups. The patients underwent pathological assessments to determine the degree of histopathological injury of the non-cancerous liver parenchyma. Group A included 37 cases, group B 17 cases and group C 10 cases. There were no significant differences among the groups regarding the number of OBC cycles and duration of OBC cessation. Sinusoidal injury was observed in 27.0, 29.4 and 30.0% of the cases in groups A, B and C, respectively; the differences were not statistically significant (P=0.479). Steatohepatitis was observed in 35.1, 35.3 and 40.0% of the cases in groups A, B and C, respectively; the differences were not statistically significant (P=0.958). There was no significant correlation between age and sinusoidal pathological score (r=-0.102, P=0.423) or non-alcoholic fatty liver disease activity score (r≤0.001, P=0.997). Therefore, the development of CALI following OBC treatment in CRLM was not found to differ by age. [ABSTRACT FROM AUTHOR]

Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix-loop-helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis-related markers in human esophageal squamous cell carcinoma TE-11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively. Following cisplatin treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited expression of the pro-apoptotic factor Bim and slightly increased the anti-apoptotic factor Bcl-xL. However, overexpression of DEC1 during cisplatin treatment failed to affect expression of these markers. Additionally, overexpression of DEC2 improved cell viability and decreased cell apoptosis induced by cisplatin. These results suggested that DEC2 exhibits anti-apoptotic effects in TE-11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may therefore have therapeutic potential for the treatment of esophageal cancer, in combination with cisplatin. [ABSTRACT FROM AUTHOR]

Pathological stage is the most important prognostic factor in patients with lung cancer, and is defined according to the tumor node metastasis classification system. The present study aimed to investigate the clinicopathological significance of lymphatic invasion in 103 patients who underwent surgical resection of lung squamous cell carcinoma (SqCC). The patients were divided into two groups, according to the degree of lymphatic invasion: Those with no or mild lymphatic invasion (ly0-1) and those with moderate or severe lymphatic invasion (ly2-3). Ly2-3 was associated with tumor size (P=0.028), lymph node metastasis (P<0.001), venous invasion (P=0.001) and histological differentiation (P=0.047). Statistical analysis using the Kaplan-Meier method and the log-rank test indicated that overall survival was significantly reduced in patients with ly2-3 compared with those with ly0-1 (P<0.001). Multivariate analysis identified ly2-3 as an independent predictor of mortality (hazard ratio, 2.580; 95% confidence interval, 1.376-4.839). In conclusion, moderate or severe lymphatic invasion (ly2-3) indicated a high malignant potential and may be considered an independent predictor of poor prognosis in patients with SqCC of the lung. [ABSTRACT FROM AUTHOR]

Several studies have noted benign thecoma-fibroma tumors with positive F-18 fluorodeoxyglucose (FDG) accumulation mimicking malignant ovarian tumors following F-18 FDG positron emission tomography (PET). The present study analyzed four cases with false-positive F-18 FDG PET/computed tomography (CT) diagnoses of thecoma-fibroma tumors as malignant tumors due to F-18 FDG accumulation, compared with eight cases of FDG-positive ovarian cancers and two cases of FDG-negative fibromas. Hypoxia inducible factor (HIF)-1α expression was examined in the six thecoma-fibroma tumors using reverse transcription-polymerase chain reaction (RT-PCR). The four F-18 FDG-positive cases exhibited higher cellularity, maximum standard uptake and signal intensity on T2-weighted imaging, and gadolinium (Gd) enhancement using magnetic resonance imaging than the two FDG-negative fibroma cases. In the F-18 FDG-positive thecoma-fibroma group, Ki-67 expression was low and LAT1 expression was not identified, ruling out the diagnosis and potential for malignancy. However, considerable glucose transporter 1, HIF-1α, and vascular endothelial growth factor expression was observed. HIF-1α expression was elevated in all four false-positive cases by RT-PCR. From these results, it was hypothesized that hypoxia due to elevated cellularity may stimulate HIF-1α expression and be associated with F-18 FDG accumulation in F-18-positive thecoma-fibroma tumors. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a common malignant disease, the incidence of which is increasing worldwide, therefore, identifying novel prognostic factors to improve adjuvant therapeutic strategies or postoperative monitoring is required. Angiogenesis, which is assessed by microvessel density (MVD), is significant in tumor growth and metastasis. However, the association between angiogenesis and clinical outcome remains controversial. In the present study, 84 surgically resected cases of colorectal cancer were examined to clarify the clinicopathological significance of vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cluster of differentiation (CD)34 expression levels. VEGF expression was identified to be significantly correlated with TP expression (r=0.45; P<0.0001) and MVD in the high VEGF expression group was observed to be significantly greater than that in the low VEGF expression group (P=0.0194). In the Dukes' stage D group, the MVD in the high TP expression group was significantly greater than that in the low TP expression group (P=0.0149). High VEGF expression was subsequently correlated with a short overall survival rate for patients exhibiting lymph node metastasis (P=0.0128); however, there was no significant difference in overall survival rate regarding the expression levels of TP and CD34. The results of the present study indicate that VEGF expression may serve as a prognostic factor for colorectal cancer patients exhibiting lymph node metastasis. Furthermore, angiogenesis, as assessed by MVD, is an important prognostic factor for tumor growth at the primary site. [ABSTRACT FROM AUTHOR]

Ki-67 is a nuclear protein that is expressed during the G1, S, G2 and M phases of the mitotic cell cycle. A previous study categorized tumor infiltration patterns (INF), of which INFc indicated cancer nests exhibiting infiltrative growth and an unclear boundary between tumor tissue and surrounding healthy t issue. T he present study used t he K i-67 labeling index (Ki-67 LI) as an indicator of cell proliferation, in order to examine the factors affecting INF in lung squamous cell carcinoma (SqCC). SqCC specimens (89) were classified into two groups: High-grade cell proliferation (Ki-67 LI ≥30%) and low-grade cell proliferation (Ki-67 LI <30%). However, a high Ki-67 LI was significantly associated with cases that had an INFc component [INFc(+); P=0.03]. Univariate analyses indicated that INFc(+) was a predictor of venous invasion [P=0.032; odds ratio (OR), 2.615; 95% confidence interval (95% CI), 1.085-6.305], scirrhous stromal type (P<0.001; OR, 6.462; 95% CI, 2.483-16.817) and high Ki-67 LI (P=0.018; OR, 12.543; 95% CI, 1.531-102.777). Multivariate logistic analyses indicated that high Ki-67 LI was the strongest predictor of INFc(+) (P=0.028; OR, 8.027; 95% CI, 1.248-51.624). In conclusion, high-grade cell proliferation activity may contribute to aggressive infiltrative growth of lung SqCC. [ABSTRACT FROM AUTHOR]

Podoplanin is a small membrane mucin, which is involved in cell migration and cancer cell invasion. However, the roles of podoplanin in esophageal squamous cell carcinoma (ESCC) are poorly understood. In the present study, 139 cases of surgically resected ESCC were analyzed and the clinicopathological significance of podoplanin membrane expression in ESCC was demonstrated. Podoplanin expression was positive in 66.2% (92/139) of ESCC samples; with weak expression in 32.4% (45/139), and strong expression in 33.8% (47/139). Membrane expression of podoplanin was significantly associated with tumor status (P=0.001), venous invasion (P=0.035) and Union for International Cancer Control stage (P=0.029). Patients who exhibited strong podoplanin expression, were shown to have a poorer prognosis [hazard ratio (HR), 3.949; 95% confidence interval (CI), 2.001-7.794]. Expression of vimentin, a mesenchymal marker, was detected in 49 cases (35.3%) and was associated with venous invasion (P=0.020). Vimentin-positive cases were also more likely to have a worse prognosis than vimentin-negative cases (HR, 2.161; 95% CI, 1.300-3.592). Podoplanin membrane expression was significantly correlated with vimentin cytoplasmic expression in ESCC (P<0.001). The present study confirmed that podoplanin and vimentin are independent predictors of mortality (HR, 3.084; 95% CI, 1.543-6.164). These results suggest that podoplanin membrane expression results in epithelial-mesenchymal transition and promotes aggressive invasion in human ESCC. [ABSTRACT FROM AUTHOR]