岸本 充

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the brain; therefore, the features of brain metastasis of PDAC are still unknown. We encountered simultaneous metastases to the brain and lung in a PDAC patient after curative surgery. Case presentation A 68-year-old man with PDAC in the tail of the pancreas underwent distal pancreato-splenectomy. He received gemcitabine as adjuvant chemotherapy for 6 months. Two months later, brain and lung metastases occurred simultaneously. Considering the systemic condition, the patient received gamma knife treatment and an Ommaya reservoir was inserted for drainage. The patient's condition gradually worsened and he received the best supportive care. To the best of our knowledge, only 28 cases in which brain metastases of PDAC were identified at the time of ante-mortem have been reported to date, including the present case. Notably, the percentage of simultaneous brain and lung metastases was higher (32%) in a series of reviewed cohorts. Thus, lung metastasis might be one of the risk factors for the development of brain metastasis in patients with PDAC. As a systemic disease, it can be inferred that neoplastic cells will develop brain metastasis via hematogenous dissemination beyond the blood-brain barrier, even if local recurrence is controlled. In our case, immunohistochemical staining showed that the neoplastic cells were positive for carbonic anhydrase 9 (CAIX), mucin core protein 1 (MUC1), and MUC5AC in the resected primary PDAC. CONCLUSION: We describe a case of simultaneous brain and lung metastases of PDAC after curative pancreatectomy, review previous literature, and discuss the clinical features of brain metastasis of PDAC.

Some cancers are related to atherosclerotic diseases; therefore, these two types of disease may share some antibody biomarkers in common. To investigate this, a first screening of sera was performed from patients with esophageal squamous cell carcinoma (ESCC) or acute ischemic stroke (AIS) for serological identification of antigens using recombinant cDNA expression cloning (SEREX). The amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method, which incorporates glutathione donor beads and anti-human IgG acceptor beads, was used to evaluate serum antibody levels. SEREX screening identified low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) as a target antigen of serum IgG antibodies in the sera of patients with ESCC or AIS. Antigens, including recombinant glutathione S-transferase-fused LRPAP1 protein, were prepared to examine serum antibody levels. AlphaLISA revealed significantly higher antibody levels against the LRPAP1 protein in patients with solid cancers such as ESCC and colorectal carcinoma and some atherosclerosis-related diseases such as AIS and diabetes mellitus compared with healthy donors. Correlation analysis revealed that the elevated serum antibody levels against LRPAP1 were associated with smoking, a well-known risk factor for both cancer and atherosclerosis. Serum LRPAP1 antibody is therefore a common marker for the early diagnosis of some cancers and atherosclerotic diseases and may reflect diseases caused by habitual smoking.

OBJECTIVES: We aimed to determine the difference in endoscopic ultrasonography (EUS) images between portal vein (PV) and arterial invasion of pancreatic cancer and to develop criteria for arterial involvement. METHODS: We reviewed EUS data of consecutive patients who underwent distal pancreatectomy from December 2010 to May 2017. We categorized the tumor-vessel relationship into 4 and 5 types, respectively, for the PV and arteries: (a) clear separation between tumor and vessel; (b) tumor border at vessel, echo-rich vessel wall uninterrupted; (c) echo-rich vessel wall interrupted; (d) vessel contour irregularity; and (e) arterial wall thickening or echogenic band surrounding the artery. We compared EUS outcomes with surgical and pathological results. RESULTS: Overall, 56 patients underwent distal pancreatectomy, of whom 22 received en bloc celiac axis resection. The pathological invasion rates of PVs and arteries were 46.2% and 0% in (c), and 72.5% and 42.4% in (d) (P = 0.046, P = 0.016), respectively. The overall sensitivity and specificity were 92.1% and 83.2%, respectively, for diagnosing venous invasion and 70.0% and 84.4%, respectively, for arterial invasion. CONCLUSIONS: Different EUS criteria may be necessary for diagnosing arterial and portal venous invasions. Criterion (d) might be appropriate for diagnosing arterial invasion.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) is a safe treatment for colorectal adenomas. However, the R0 resection rate is not sufficiently high because of inadequate resection of muscularis mucosa. We hypothesized that CSP in an underwater environment could improve this procedure by helping to safely achieve resection containing the muscularis mucosa. We have named this procedure underwater cold snare polypectomy (UCSP). We aimed to investigate the efficacy and safety of UCSP for colorectal adenomas. METHODS: Between May 2017 and April 2018, patients diagnosed with colorectal adenomas <9 mm underwent UCSP. After follow-up colonoscopy 3 weeks later, the patients post-UCSP scars were biopsied. Outcomes were compared with those of a historical control group who underwent conventional CSP in our previous study using propensity score-matching methods. RESULTS: Overall, 224 lesions in 65 patients were prospectively resected by UCSP. Pathologically, 209 lesions were adenomas (4.5 ± 1.5 mm) including one intramucosal carcinoma. Only one pathological residual adenoma was identified, but there was no significant difference in the residual rate between the UCSP and CSP groups (both 1.0%). No complications were observed. R0 resection rate and rate of area containing the muscularis mucosa in the UCSP group were significantly higher than those in the CSP group (80.2% vs 32.7%, P < 0.001; 50.0% vs 35.3%, P = 0.015). CONCLUSION: Underwater cold snare polypectomy for diminutive and small colorectal adenomas was safe and effective from the perspective of pathological complete resection, which is likely facilitated by achieving an adequate depth of resection.

A 5-year-old boy with a chromosome-9 abnormality and multiple external and visceral malformations was found in cardiopulmonary arrest during a regular visit to the hospital; he did not respond to cardiopulmonary resuscitation and died. An odontoid process fracture and calcification and fibrosis of the muscles around the superior cervical vertebra were observed during the autopsy. Postmortem computed tomography revealed an anterior dislocation of the atlas; odontoid synchondrosis fracture; and delayed, incomplete bony fusion of the odontoid process relative to his age. The cause of his death was a superior spinal cord injury. The tissue surrounding the upper cervical spine presented with myositis ossificans, suggesting a prior injury. He experienced a minor traffic accident 3 months before his death. It was concluded that the odontoid synchondrosis fracture occurred during the accident based on the incomplete bony fusion and atlantoaxial instability, which were consistent with the findings of myositis ossificans. Delayed fatal dislocation may then have occurred under the influence of a minor external force. Odontoid process abnormalities and atlantoaxial instability are common in patients with trisomy 21 and other congenital diseases; however, the condition's association with chromosome-9 abnormalities has not been reported. In children with various chromosomal abnormalities, periodic assessment of instability and morphology of the cervical spine, and a lowered examination threshold for the children at risk, could prove useful in the prevention injuries leading to fatality, and provide additional information to rule out abuse.

We recently reported the reduced ATP-sensitive potassium (KATP) channel activities in the transgenic mouse heart overexpressing the vascular type KATP channel pore-forming subunit (Kir6.1). Although dysfunction of cardiac KATP channel has been nominated as a cause of cardiomyopathy in human, these transgenic mice looked normal as wild-type (WT) during the experiment period (~20 weeks). Extended observation period revealed unexpected deaths beginning from 30 weeks and about 50% of the transgenic mice died by 55 weeks. Surface ECG recordings from the transgenic mice at rest demonstrated the normal sinus rhythm and the regular ECG complex as well as the control WT mice except for prolonged QT interval. However, the stress ECG test with noradrenaline revealed abnormal intraventricular conduction delay and arrhythmogeneity in the transgenic mouse. Fibrotic changes in the heart tissue were remarkable in aged transgenic mice, and the cardiac fibrosis developed progressively at least from the age of 30 weeks. Gene expression analyses revealed the differentiation of cardiac fibroblasts to myofibroblasts with elevated cytokine expressions was initiated way in advance before the fibrotic changes and the upregulation of BNP in the ventricle. In sum, Kir6.1TG mice provide an electro-pathological disease concept originated from KATP channel dysfunction.

A 68-year-old woman was referred to our hospital for the treatment of bile duct stone, pancreatic tumor, and pancreatic cysts. First, bile duct stone was removed using endoscopic retrograde cholangiopancreatography. By abdominal contrast-enhanced computed tomography, a 12-mm diameter tumor was found in the pancreatic body. The tumor was isodense compared with the surrounding pancreatic parenchyma in the non-contrast phase and poorly enhanced in the arterial phase; it exhibited gradual enhancement from the portal vein phase to the late phase. Numerous pancreatic cysts were also observed by contrast-enhanced computed tomography. By magnetic resonance imaging, the tumor was hypointense in T1-weighted images, isointense in T2-weighted images, and hyperintense in diffusion-weighted images. By magnetic resonance cholangiopancreatography, the main pancreatic duct was not dilated, and pancreatic cysts communicated with the main pancreatic duct. The pancreatic cysts were diagnosed as branch-type intraductal papillary mucinous neoplasm. Histopathologic assessment of the specimens obtained by endoscopic ultrasound-guided fine-needle aspiration revealed the tumor as benign pancreatic granular cell tumor. The patient was followed up without surgical resection. On contrast-enhanced computed tomography at 6 months after admission, the tumor did not show any changes in diameter or characteristics.

BACKGROUND: Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis. METHODS: First, we evaluated IMP3 expression in 77 resected specimens of pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), and chronic pancreatitis (CP). Eleven PDAC patients preoperatively underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Survival analysis of IMP3 and clinicopathological factors was performed. IMP3 and p53 expression was evaluated in another 127 EUS-FNA samples of solid pancreatic masses to compare the diagnostic value of routine and immunohistochemical staining. RESULTS: IMP3 expression was detected in 72.3%, 50%, 20%, and 0% of PDAC, malignant IPMN, benign IPMN, and CP, respectively. Evaluation of IMP3 expression in EUS-FNA specimens coincided with that in resected specimens in 10 of 11. IMP3 expression correlated with tumor differentiation in PDAC samples (p = .006) and with poor prognosis through univariate analysis (p = .045). Tumor differentiation and lymph node metastasis were significantly associated with poor prognosis through multivariate analysis. In EUS-FNA specimens, the sensitivity, specificity, and accuracy of cytohistological analysis were 80.8%, 100%, and 85.0%, respectively. IMP3 and p53 expression were detected in 80.8% and 44.9% of malignant and 0% and 5% of benign lesions. Combined with IMP3 immunostaining, the sensitivity, specificity and accuracy of cytohistological analysis significantly increased to 87.9%, 100%, and 90.8% (p = .016), respectively. Meanwhile, p53 staining had no impact on the results. CONCLUSIONS: IMP3 immunohistochemical staining can improve the diagnostic accuracy of EUS-FNA for malignant pancreatic tumors.

This retrospective study aimed to assess the diagnostic performance of contrast-enhanced ultrasound with Sonazoid (S-CEUS) for liver metastasis. We enrolled in this study 98 patients with 148 histologically proven liver lesions, with 121 metastases and 27 non-metastases. The S-CEUS technique showed sensitivity in 95.0% (115 of 121), specificity in 44.4% (12 of 27) and accuracy in 85.8% (127 of 148) for the diagnosis of metastasis. Higher body mass index had a negative influence on the positive predictive value and accuracy, and a greater depth of the lesion had a negative influence on the accuracy. The management was changed in 8 patients (8.2%) because of S-CEUS findings. In conclusion, the addition of S-CEUS may offer a great benefit by improvement of the quality of diagnosis and management for patients with cancer who have a tentative diagnosis of liver metastasis by contrast-enhanced computed tomography. (C) 2017 World Federation for Ultrasound in Medicine & Biology.

Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1β were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) is useful for the diagnosis of cancer as it presents a clear contrast between cancerous and non-cancerous tissue. The present study investigated the limitations and advantages of DWIBS/T2 with regards to the diagnosis of colorectal polyp (CP) or cancer (CRC). The current study included patients diagnosed with CP or CRC following colonoscopy, who were subjected to DWIBS/T2 between July 2012 and March 2015. Patient records were analyzed retrospectively. Patients were subjected to DWIBS/T2 when they presented with abdominal cancers or inflammation. Colonoscopy was performed as part of screening, or if patients had suspected colon cancer or inflammatory bowel disease. A total of 8 male and 7 female patients were enrolled in the present study. All patients, with the exception of one who had been diagnosed with CRC following colonoscopy, had positive results and all patients diagnosed with CP following a colonoscopy, with the exception of one, had negative results on DWIBS/T2. Thus, CRC was detected by DWIBS/T2, while CP was not (P=0.0028). The diameter of CRC lesions was significantly larger than that of CP (P<0.0001) and that of lesions positive on DWIBS/T2 was significantly larger than that of negative lesions (P=0.0004). The depth of invasion tended to be greater for lesions positive on DWIBS/T2 compared with that of negative ones. This indicated that DWIBS/T2 may be suitable for the detection of CRC but not for detection of CP. The results of DWIBS/T2 may also be affected by lesion diameter and depth of invasion.

The present study investigated the potential utility of contrast-enhanced abdominal ultrasonography (CEUS), using Sonazoid™, in colorectal cancer (CRC). Three patients were subjected to CEUS with Sonazoid™. Surgical specimens were immunostained for CD31. Numbers of blood vessels positive for CD31 were analyzed in each of five fields at ×400 magnification and averaged to determine blood vessel density. Blood vessel density was compared between non-tumorous and tumorous areas. Prior to the administration of Sonazoid™, CRC was illustrated as irregular-shaped wall thickening. One minute after the administration of Sonazoid™, the majority of the thickened wall was enhanced, while some parts of the thickened wall remained unenhanced. Blood vessel densities of non-tumorous and tumorous areas in patient two were 25.2±2.5 and 5.2±1.1 (P<0.0001). Blood vessel densities of non-tumorous and tumorous areas in patient three were 19.0±3.1 and 2.2±0.8 (P<0.0001). Tumorous areas of CRC were not enhanced 1 min after the administration of Sonazoid™. Blood vessel density was lower in tumorous areas compared with non-tumorous areas, as evidenced by immunohistochemistry for CD31. These findings suggest that CEUS may be useful for the determination of the extent of CRC.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) yields positive results for cancer against the surrounding tissues. The combination of DWIBS and T2-weighted images (DWIBS/T2) in the diagnosis of gastrointestinal tract cancers was retrospectively analyzed in the present study. Patients were subjected to magnetic resonance imaging after cancer was diagnosed through specimens obtained via biopsy or endoscopic mucosal resection. Sixteen patients were assessed between July, 2012 and June, 2013 and the correlation between detection with DWIBS/T2 and T staging was analyzed. Regarding patients who underwent surgery, the correlation between detection with DWIBS/T2 and the diameter or depth of invasion was analyzed. All cancers that had advanced to >T2 stage were detectable by DWIBS/T2, whereas all cancers staged as <T1 were not (P<0.0001). Tumors that were undetected by DWIBS/T2 had a mean diameter of 1.53±0.25 cm, whereas those detected had a mean diameter of 3.63±1.88 cm; however, the difference was not statistically significant (P=0.1053). Cancers invading beyond the muscularis propria were detectable by DWIBS/T2, while those which had not invaded the mucosa were not (P=0.0476). In conclusion, DWIBS/T2 was able to positively identify gastrointestinal tract cancers at an advanced stage (>T2) or invading beyond the muscularis propria.

Patient records were retrospectively analyzed to elucidate the characteristics of patients with colorectal cancer (CRC) diagnosed with screening abdominal ultrasound (US). Patients diagnosed with CRC using abdominal US [localized irregular wall thickening (W) or a hypoechoic mass with a hyperechoic mass (M)] were enrolled. The patients were subjected to colonoscopy and treated surgically between March, 2010 and January, 2015. A total of 5 men (aged 74.0±0.8 years) and 10 women (aged 73.0±12.0 years) were analyzed. Stratification was analyzed with abdominal US. The threshold value of wall thickness to diagnose CRC was investigated with receiver operating characteristic (ROC) curve analysis. The average wall thickness was 2.8±0.4 mm in the surrounding normal tissue and 12.7±5.2 mm in CRC (one-way analysis of variance, P<0.0001). The wall was significantly thicker in CRC compared with the normal colonic wall. The calculated threshold value was 4.3 mm for the diagnosis of CRC. Stratification was preserved in W, while it was lost in M (Chi-squared test, P=0.0196). The hemoglobin concentration was lower, while the C-reactive protein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were elevated above normal values. The threshold value was 4.3 mm for the diagnosis of CRC with abdominal US.

Differentiation between adenomyomatosis (ADM) and cancer of the gallbladder is necessary during diagnosis. Diffusion-weighted whole body imaging with background body signal suppression (DWIBS) images are able to indicate cancer and inflammation. The fusion of a DWIBS with a T2 weighted image (DWIBS/T2) facilitates both functional and anatomical investigations. In the present study, patient records and images from patients with surgically confirmed ADM from April 2012 to October 2014 were analyzed retrospectively. The enrolled patients, including 6 men (64.2±13.1 years) and 4 women (57.3±12.4 years) were subjected to DWIBS/T2 during routine clinical practice. The diagnosis of ADM was based on magnetic resonance cholangiopancreatography, transabdominal ultrasonography, and endoscopic ultrasonography; ADM was diagnosed definitively when cystic lesions were observed, indicating the Rokitansky-Aschoff sinus. A single patient was indicated to be positive by DWIBS/T2 imaging. The Rokitansky-Aschoff sinus revealed a relatively high signal intensity; however, it was not as strong as that of the spleen. The signal intensity was also high on an apparent diffusion coefficient map, suggesting T2 shine-through. The thickened wall displayed low signal intensity. The aforementioned results indicate that ADM may be negative upon DWIBS/T2 imaging; one false positive case was determined to be ADM, accompanied by chronic cholecystitis. The majority of patients with ADM displayed negative findings upon DWIBS/T2 imaging, and chronic cholecystitis may cause false positives.

Ellis-van Creveld (EVC) syndrome is a rare autosomal recessive disorder characterized by hypoplastic nails, polydactyly, and achondroplasia. Patients usually exhibit normal cognitive function and no remarkable developmental delay. We herein present an unusual case of EVC syndrome. A Japanese 2-year-old boy was born at term, but immediately developed severe respiratory failure due to thorax deformity, postaxial polydactyly and nail hypoplasia. We identified a novel pattern of germinal compound heterozygous nonsense EVC2 mutations of c.1814C > A (p. S605X) and c.2653C > T (p. R885X), leading to the diagnosis of EVC syndrome. Interestingly, he also had severe developmental delay, and suddenly developed excessive abdominal distension at the age of 2. On surgery, extensive necrotic bowel with chronic intestinal pseudo-obstruction was noted. This is, to our knowledge, a most severe phenotype of EVC syndrome, illustrating that the specific pattern of EVC2 compound heterozygous mutations may cause severe developmental delay and intestinal malfunction.

BACKGOUND: We have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC. METHODS: The subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC. RESULTS: Reduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy. CONCLUSIONS: Preoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC.

Gastric cancer is occasionally diagnosed using transabdominal ultrasonography (US) during screening or investigation of patients with abdominal symptoms. Therefore, the present study analyzed the association of the tumor diameter, pathological T (pT) staging and depth of invasion with the detection of gastric cancer using US. Patient records were analyzed retrospectively and 13 patients were enrolled, who underwent US screening prior to endoscopic mucosal resection, endoscopic submucosal dissection or surgery. In total, 5 patients were diagnosed with gastric cancer using US (positive detection group), while US was unable to detect the gastric cancer in 8 patients (negative detection group). The tumor diameter and depth of invasion were determined by pathologists. One-way analysis of variance or the χ2 test was performed. Wall thickness in gastric cancer cases ranged between 7 and 20 mm (mean, 12.2±5.9 mm), as measured using abdominal US. The hemoglobin level was significantly lower in the positive detection patients compared with the negative detection patients (P=0.0455). In addition, the diameters of the gastric wall in the negative and positive detection patients were 24.5±16.4 and 54.4±26.2 mm, respectively (P=0.0266). These results indicate that gastric cancer in the positive detection patients were at a more advanced-stage compared with that in the negative detection patients. Furthermore, gastric cancer with a stage over pT2 was diagnosed using abdominal US (P=0.0242), whereas stage pT1a gastric cancer was not detected by abdominal US. Gastric tumors invading deeper than the submucosa were diagnosed using US (P=0.0242). However, the gastric cancer cases limited to the mucosa remained undetected. In conclusion, the detection of gastric cancer correlated well with the tumor diameter, pT staging and depth of invasion.

PURPOSE: Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) strongly contrasts cancerous tissue against background healthy tissues. Positron emission tomography/computed tomography (PET/CT) applies the uptake of 18-fluorodeoxyglucose in the diagnosis of cancer. Our aim was to compare DWIBS/T2 and PET/CT in patients with upper gastrointestinal cancers. METHODS: Patient records, including imaging results from July 2012 to March 2015, were analyzed retrospectively. Four men (age, 72.5 ± 5.3 years) and ten women (age, 71.6 ± 4.0 years) were enrolled in this study. The numbers of patients with esophageal cancer, gastric cancer, gastrointestinal stromal tumor, and duodenal cancer were one, eight, three, and two, respectively. RESULTS: Six out of eight patients with gastric cancer had positive results on both DWIBS/T2 and PET/CT. The diameter and depth of invasion of gastric cancer was larger in patients with positive DWIBS/T2 and PET/CT findings than those with negative findings. These results suggested that patients with gastric cancer with larger pixel numbers might tend to show positive results with DWIBS/T2. CONCLUSIONS: DWIBS/T2 and PET/CT have similar sensitivity for the diagnosis of upper gastrointestinal cancer. The diameter and depth of invasion affected the detectability of gastric cancer.

Anti-mitochondrial M2 antibody (AMA-M2) is specific to primary biliary cirrhosis (PBC), but can also be found in certain patients with autoimmune hepatitis (AIH). Effective methods of differentiating between PBC and AIH are required, as their clinical course and management are different. Titers of AMA-M2 were analyzed before and after follow-up in patients with PBC or AIH. Patients who underwent liver biopsy and were diagnosed with either AIH (10 patients) or PBC (3 patients) were enrolled in the study. The AMA-M2 antibody titers of these patients were analyzed upon hospital admission. AMA-M2 reacted with the pyruvate dehydrogenase complex-E2, branched-chain 2-oxo acid dehydrogenase complex and 2-oxoglutaric acid dehydrogenase complex in the assay utilized for this study. The cut-off value for AMA-M2 was 5. Six AIH patients were AMA-M2(-) and 4 were AMA-M2(+). The titer for the AIH patients who were AMA-M2(+) was 24.8±14.8, compared with 324±174 in the patients with PBC (P=0.0138). Three AMA-M2(+) AIH patients were followed-up after liver biopsy. The AMA-M2 levels had decreased in all 3 patients, becoming undetectable in 2 of them. In conclusion, certain patients with AIH in this study were found to be AMA-M2(+), but the titers were significantly lower than those in the patients with PBC. At follow-up, the AIH patients exhibited decreased AMA-M2 titers.

Napsin A is a reliable marker for pulmonary adenocarcinoma and is expressed in a subset of ovarian clear cell carcinomas (O-CCCs), endometrial (EM) CCCs, and endometrioid carcinomas (EC). We investigated napsin A levels in O-CCC and EM-CCC and compared these with levels in other nonmucinous ovarian carcinomas and EM-EC, respectively. Napsin A, thyroid transcription factor (TTF)-1, paired box (PAX) 8, and cancer antigen (CA) 125 expression was evaluated in 111 ovarian and uterine carcinoma cases (22 O-CCC, 15 EM-CCC, 13 ovarian EC (O-EC), 39 high-grade serous carcinoma [HGSC], and 22 EM-EC) using immunohistochemistry. Napsin A immunoreactivity was observed in 21 (95.5%) of 22 O-CCC and 10 (66.7%) of 15 EM-CCC cases but was rare in O-EC and EM-EC (7.7% and 4.5%) and undetectable in HGSC cases. Thyroid transcription factor 1 was not expressed in O-CCC but was detected in 1 (6.7%) of 15 EM-CCC, 3 (23.1%) of 13 O-EC, 2 (5.1%) of 39 HGSC, and 1 (4.5%) of 22 EM-EC cases. All 111 cases examined were positive for PAX8, whereas 3 (20.0%) of 15 of EM-CCC and 1 (4.5%) of 22 EM-EC cases were negative for CA125. There were no napsin A/TTF-1 double-positive cases, except for 1 EM-CCC, in which cells had a focal expression pattern. All napsin A- and/or TTF-1-positive cases expressed PAX8 and CA125. In conclusion, napsin A is frequently expressed in O-CCC and EM-CCC, rarely in O-EC and EM-EC, and never in HGSC cases. These findings confirm the importance of using a panel of antibodies that includes napsin A, TTF-1, and PAX8 when evaluating metastatic carcinomas of unknown origin, particularly when gynecologic and pulmonary adenocarcinomas are included in the differential diagnosis.

BACKGROUND: Laterally spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy. We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs. METHODS: The expression of 168 genes in 41 colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip [pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or more in diameter] was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to Ip-adenoma, by hierarchical and K-means clustering. To confirm the results of the array analysis, using an additional 60 samples (38 LST-adenoma, 22 Ip-adenoma), we determined the localization of the gene product by immunohistochemical staining. RESULT: The expression of 129 genes differed in colorectal tumors from normal mucosa by PCR array analysis. As a result of K-means clustering, the expression levels of five genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25, were found to be significantly up-regulated (p < 0.05) in LST-adenoma, compared to Ip-adenoma. Immunohistochemical analysis showed that the BCL2L1 protein was significantly and meaningfully up-regulated in LST-adenoma compared to Ip-adenoma (p = 0.010). With respect to apoptosis status in LST-Adenoma, it assumes that BCL2L1 is anti-apoptotic protein, the samples such as BCL2L1 positive and TUNEL negative, or BCL2L1 negative and TUNEL positive are consistent with the assumption. 63.2 % LST-adenoma samples were consistent with the assumption. CONCLUSIONS: LSTs have an unusual profile of gene expression compared to other tumors and BCL2L1 might be concerned in the organization of LSTs.

We present a case of orbital mucosa-associated lymphoid tissue (MALT) lymphoma accompanied by a serous retinal detachment (SRD). A 44-year-old man who developed uveitis accompanied by a SRD in the right eye was referred to the Chiba National Hospital. B-mode ultrasonography and magnetic resonance imaging (MRI) showed a thickened choroidal membrane and a retrobulbar mass. Although topical steroid treatments improved the inflammation, the SRD did not improve. He was then referred to the Chiba University Hospital. Two months later, the retrobulbar mass had increased, and a partial resection biopsy combined with flow cytometry was performed. The final diagnosis was MALT lymphoma. After R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy, signs of the tumour could not be detected and the SRD was reduced. We conclude that the SRD was most likely due to the infiltration of lymphoma cells and also to choroidal circulatory disturbances. Retrobulbar malignant lymphomas associated with a SRD are very rare and difficult to diagnosis without biopsy, but because early diagnosis is helpful in deciding the appropriate therapy, we recommend partial biopsy.

BACKGROUND AND AIMS: Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study. We aimed to evaluate the pre-malignant potentiality of LRNs and DNs with a greater number of cases and longer follow-up periods. METHODS: From 1982 to 2005, 1,500 consecutive nodular lesions up to 2 cm in diameter were subjected to US guided thin-needle biopsy in cirrhotic patients at Chiba University Hospital. Of these lesions, 68 LRNs in 60 cases and 20 DNs in 22 cases were followed up for more than 6 months without any anti-cancer therapy. The last US examination was in 2010. The total study period was 28 years. We analyzed the histological findings and the clinical data of all cases retrospectively. The outcome of the lesions was examined. RESULTS: The mean follow-up period was 38.9 (16-119) months in LRNs and 31.9 (6-101 months) in DNs. Rate of nodule enlargement was higher in DNs (8/24 nodules, 33%) than LRNs (11/68 nodules, 16 %), (p = 0.0743, not significant). Rate of malignant transformation was also higher in DNs (10/24 nodules, 42%) than LRNs (9/68 nodules, 13%), (p = 0.0040, significant). The rate of disappearance in images was similar between LRNs and DNs. CONCLUSIONS: We should recognize LRN as low risk pre-malignant lesions whereas DNs as high risk lesions.

This 18-year-old female was incidentally found to have a left parotid gland tumor when she visited a local doctor with a complaint of pollen allergy. Aspiration cytology, performed twice, failed to give a definite diagnosis. The patient was referred to our hospital. The tumor was well-demarcated on ultrasonography and showed a heterogeneous image on MRI. Pleomorphic adenoma with hyalinized fibrosis was suspected on a core needle biopsy. The patient underwent superficial lobectomy of the left parotid gland. Gross examination of the resected specimen showed a 21mm-sized well-demarcated, solid and white tumor. Microscopically, it showed irregularly defined lobules composed of abundant hyalinized fibrous tissue and variably sized collections of ducts with cystic change. Hyperplasia of ductal elements with a cribriform pattern and acinar cells with eosinophilic cytoplasmic granules were focally seen. Immunohistochemistry demonstrated preservation of the biphasic epithelial architecture with the basally situated cells of the ductal element positively stained for myoepithelial markers. We diagnosed the present case as sclerosing polycystic adenosis. At 3 years' follow-up, the patient is free of recurrence and metastasis. Close follow-up, however, is necessary since there have been a few reported cases of SPA that recurred, harbored carcinoma within the lesion, or was shown to be a clonal process.

We report a rare case of a 46-year-old woman with cholangiocarcinoma derived from remnant intrapancreatic bile duct arising 32 years after the excision of a congenital choledochal cyst. She had undergone anastomosis of the choledochal cyst and duodenum at birth, excision of the choledochal cyst and hepaticoduodenostomy with jejunal interposition at 14 years of age as well as the excision of an infectious cyst around the anastomosis site at 21 years of age. At 29 years of age, she was diagnosed with a chronic hepatitis C virus (HCV) infection and was referred to our hospital for treatment. She did not consent to interferon-based therapy against the HCV infection. At 46 years of age, she experienced epigastric discomfort. A dynamic CT revealed multiple tumors in the liver, a tumor in the head of the pancreas as well as lymph node metastases in the mediastinum and abdominal cavity. A liver tumor biopsy revealed adenocarcinoma, and she was clinically diagnosed with cholangiocarcinoma derived from remnant intrapancreatic bile duct with multiple metastasis in the liver and lymph node metastasis. She requested palliative therapy and eventually died during the treatment course. The autopsy specimen revealed a tumor in the head of the pancreas, and on the basis of local existence and the pattern of metastasis, it was confirmed as cholangiocarcinoma derived from remnant intrapancreatic bile duct. A microscopic examination revealed a poorly differentiated adenocarcinoma. This report provides information on a case of cholangiocarcinoma derived from remnant intrapancreatic bile duct arising after the excision of congenital choledochal cyst that was assessed pathologically. (C) 2015 S. Karger AG, Basel

BACKGROUND/AIMS: The aim of this study was to identify factors affecting the detection of colorectal cancer (CRC) and colon polyps (CPs) using abdominal ultrasonography (US). METHODOLOGY: Patient records were analyzed retrospectively. Those diagnosed as having either CRC or CPs by colonoscopy performed after screening abdominal US were enrolled. The diagnostic criterion for CRC was an irregularly thickened wall or mass. CPs were diagnosed as spherical or ovoid hypoechoic lesions arising within the colonic lumen as seen on abdominal US. RESULTS: Sixteen patients had a total of 16 CRC lesions and 11 patients had a total of 17 CPs. All CRC lesions invaded deeper than the subserosa. Cancer cell invasion limited to the submucosa was noted in the two 1.5-cm CPs. Detection of these lesions was not associated with invasion to lymph or blood vessels. These results suggest that wall thickening might be the consequence of cancer cells invading below the subserosa, thereby resulting in the lesions becoming detectable on abdominal US. CONCLUSIONS: Detection of CRC and CPs on abdominal US was associated with lesion size and depth of invasion.

We report a case of pancreatic hamartoma-like solitary fibrous tumor which was differentiated from pancreatic hamartoma with the detection of NAB2-STAT6 fusion, a specific mutation for solitary fibrous tumors. A pancreatic well-demarcated solid nodule, 21 × 17 mm, of 82-year-old man was surgically enucleated. Microscopic findings were close to a pancreatic hamartoma that consisted of sparsely distributed pancreatic ducts and acini in heavily collagenized fibrous stroma. Neither islet nor peripheral nerve existed in the tumor. The fibroblastic cells in the stroma were immune-positive for CD34, CD99, and bcl-2. But these expressions were not decisive in the differentiation between solitary fibrous tumor and pancreatic hamartoma, because CD34 was positive for both tumors, and CD99 and bcl-2 expressions were not elucidated in the previous cases of pancreatic hamartomas. Thus, we evaluated NAB2-STAT6 fusion. The fibroblastic cells were positive for STAT6 and sequencing analysis revealed the gene fusion between NAB2 exon 4 and STAT6 exon 2, with which the final diagnos is of solitary fibrous tumor was achieved. In conclusion, detection of NAB2-STAT6 fusion has a great diagnostic value for pancreatic solitary fibrous tumors with hamartoma-like features.

BACKGROUND AND AIM: Preoperative assessment of longitudinal extension of cholangiocarcinoma (CCA) is essential for making decisions concerning surgical resection and selecting operative procedures. We evaluated the accuracy of peroral video-cholangioscopy (PVCS) in diagnosing longitudinal extension of CCA. METHODS: Patients with CCA who underwent preoperative PVCS were considered for this study. We evaluated the accuracy of PVCS in diagnosing longitudinal extension of perihilar cholangiocarcinoma (PCCA) and distal extrahepatic cholangiocarcinoma (DCCA) to the secondary biliary radicles and confluence of the hepatic ducts, respectively, on the hepatic side and to the intrapancreatic common bile duct on the papillary side. Diagnostic accuracy was determined by comparing the results with those of histopathological analyses of surgical specimens. RESULTS: Forty-three consecutive patients were enrolled. The cholangioscope could not be advanced into the hepatic side in eight of the 25 patients with PCCA and in five of the 18 patients with DCCA. The accuracy of PVCS in diagnosing longitudinal extension of CCA on the hepatic and papillary sides was 82.4% and 92.0%, respectively, in patients with PCCA and 92.3% and 100%, respectively, in patients with DCCA. PVCS accurately detected longitudinal extension of CCA to the hepatic and papillary sides that was not detected previously by endoscopic retrograde cholangiography in 20.0% and 11.6% patients, respectively. CONCLUSIONS: PVCS proved useful for the preoperative assessment of longitudinal extension of CCA. Therefore, it can aid surgeons in deciding surgical resectability and selecting operative procedures. This, in turn, may impact overall patient prognosis.

BACKGROUND AND AIM: Gastric ulcer healing is a complex process involving cell proliferation and tissue remodeling. Sonic hedgehog (Shh) activates the Shh signaling pathway, which plays a key role in processes such as tissue repair. Shh and interleukin 1β (IL1β) have been reported to influence the proliferation of gastric mucosa. We evaluated the relationships between the speed of gastric ulcer healing and the levels of expression of Shh and IL1β. METHODS: The study included 45 patients (mean age 71.9 ± 9.0 years; M/F, 30/15) who underwent endoscopic submucosal dissection (ESD) for gastric cancer, followed by standard dose of oral proton-pump inhibitor for 4 weeks. Subsequently, the size of ESD-induced artificial ulcers were measured to determine the speed of gastric ulcer healing, and regenerating mucosa around the ulcers and appropriately matched controls were collected from patients by endoscopic biopsy. Polymerase chain reaction (PCR) array analysis of genes in the Shh signaling pathway was performed, and quantitative reverse transcription (RT)-PCR was used to measure IL1β mRNA. RESULTS: The levels of Shh and IL1β mRNA were 3.0 ± 2.7-fold and 2.5 ± 2.5-fold higher, respectively, in regenerating mucosa of artificial ulcers than in appropriately matched controls, with the two being positively correlated (r = 0.9, P < 0.001). Shh (r = 0.8, P < 0.001) and IL1β (r = 0.7, P < 0.005) expression was each positively correlated with the speed of gastric ulcer healing, but multivariate analysis showed that Shh expression was the only significant parameter (P = 0.045). CONCLUSIONS: Expression of Shh was correlated with the speed of gastric ulcer healing, promoting the regeneration of gastric mucosa.

IgG4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by marked infiltration of IgG4-positive (+) plasma cells into affected organs, but the concept of this disease has only recently been established. Coronary vasculitis is a rare disease that can cause sudden death, and it has recently been reported that IgG4-RD may be associated with vasculitis, including periarteritis and coronary disease. In this paper we report an autopsy case of sudden death of a man in his thirties, in which coronary periarteritis with features of IgG4-related periarteritis was detected. IgG4-RD was suspected from the presence of the following histopathological features: (1) markedly thickened adventitia and marked infiltration of the adventitia and periarterial fat by lymphocytes and plasma cells; and (2) infiltration of IgG4-positive plasma cells (ratio of IgG4+ cells to IgG4+ cells of >40 %, 50 IgG4+ plasma cells per high-power field) on immunostaining. The etiology and pathophysiology of IgG4-RD and IgG4-related periarteritis are still unclear, and further investigation of these conditions and their association with coronary lesions is needed. Careful consideration should be given to the possible presence of IgG4-RD when forensic pathologists encounter cases of sudden death accompanied by coronary periarteritis.

A 61-year-old woman presenting with nausea was found by gastrointestinal endoscopy to have an ulcerative lesion in the second portion of the duodenum. Histological examination of a biopsy specimen revealed poorly differentiated adenocarcinoma. Computed tomography showed a hypovascular mass in the hepatic posterior section. She was recommended to receive chemotherapy following a diagnosis of duodenal cancer with synchronous liver metastasis. After receiving a second and third opinion elsewhere, the patient was finally referred to our hospital 4 months after the symptom onset. Based on a diagnosis of duodenal cancer and a hepatic mass that could not be definitively diagnosed, we conducted pancreaticoduodenectomy and resection of the right posterior hepatic section. Histologically, there was no evidence of viable cancer cells in the resected duodenum or liver, but granulomas with necrosis were observed. In the necrotic area, ghost cells were observed, which resembled cancer cells biopsied from the duodenum preoperatively and were immunohistochemically positive for cytokeratin. These findings suggested that the duodenal cancer and liver metastasis spontaneously disappeared without any treatment. Spontaneous regression of gastrointestinal cancer is rare, and the present report is the first to document a case of spontaneous regression of duodenal cancer. © 2014 The Japanese Society of Gastroenterological Surgery.

A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC) 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.

It has been established that nuclear pseudostratification of the neural epithelium in vertebral embryos is caused by interkinetic nuclear migration, a cell cycle-dependent regulation of nuclear movement, during which the G2/M-phase nuclei move apically before returning basally in the G1/S phase. Here we demonstrate the cell cycle-related nuclear location characteristic of interkinetic nuclear migration in human neoplastic and non-neoplastic pseudostratified glands. Immunohistochemical analysis with phosphohistone H3 (a G2/M-phase marker) and Ki67 was performed on fetal tissues, proliferative-phase endometrium (5 cases), and colonic adenomas (12 cases). In all cases, G2/M nuclei were significantly located apically, whereas Ki67-positive nuclei were widely distributed along the basal-apical axis. In the proliferating zone of the normal colon mucosa, elongated nuclei in the G2/M phase were occasionally found on the apical side of the cells. These results suggest that the interkinetic nuclear migration occurs in association with cell proliferation in both neoplastic and non-neoplastic glands.

肝未分化肉腫(UES)を2例経験した。症例1は13歳男子で、1週間前から右側腹部痛が出現した。自宅安静にて軽快するも、入浴後に増悪した。腹部エコー(US)にて肝内腫瘤を認め、腫瘍内出血が疑われた。年齢、画像的特徴からUESを疑い、右葉部分切除を行った。その後、2年間、無再発である。症例2は13歳女子で、半年ほど前から腹圧をかけた時の心窩部痛と腫瘤を自覚した。激烈な腹痛が出現し腹部腫瘤および腫瘍内出血を疑った。UESが疑われるも、確定診断のために開腹生検を行った。腹水細胞診ではclass IIIであった。腫瘍前面から生検を行い、UESと診断した。化学療法1コース後の造影CTでは、腫瘍は左葉内にて増大していたが、造影効果を有する部分は縮小した。増大傾向と判断し、拡大左葉切除を行った。その後化学療法を行い、2年間、無再発である。

Adamantinoma-like Ewing family tumor (EFT) is a rare subset of EFTs showing mixed features of Ewing sarcoma and adamantinoma of the long bones. All currently reported cases of the adamantinoma-like type have been associated with bone. Recently, a unique type of EFT was reported showing complex epithelial differentiation associated with the vagus nerve. Here we describe another unique type of EFT arising in the soft tissue of the neck associated with the vagus nerve. An 11-year-old girl presented to our hospital with a neck tumor on her right side. Surgical resection was performed, and histopathologic examination demonstrated a high-grade malignant neoplasm. The tumor was composed of sheets of small round proliferating cells, basaloid tumor nests with marked squamous differentiation, biphasic growth pattern with epithelioid tumor nests, and spindle cell proliferation. Immunohistochemically, the tumor cells showed diffuse expression of CD99 and FLI-1. In addition, small round cells and basaloid/squamoid components were immunoreactive for AE1/AE3, CAM5.2, cytokeratin 5/6, high-molecular weight keratin, p63, and p40 (ΔNp63). Reverse transcription polymerase chain reaction and direct sequencing analysis revealed that the tumor harbored a t(11;22) translocation, involving EWSR1 and FLI-1, which are characteristic of EFTs. According to these findings, our case has characteristics of both a subset of adamantinoma-like EFT and EFT with complex epithelial differentiation. We suggest that EFT with complex epithelial differentiation is in a common spectrum with the adamantinoma-like type and that adamantinoma-like EFTs can arise in soft tissue, leading to difficulty in differential diagnosis with malignant epithelial tumors.

This study retrospectively analyzed the clinical outcomes of endoscopic resection of 26 sporadic (i. e., not associated with polyposis syndrome) nonampullary duodenal lesions representing high-grade dysplasia or intramucosal carcinoma (duodenal HGD/IMC) in 23 patients. No severe complications such as perforation were observed, but three cases of delayed bleeding were seen. The use of endoscopic clips significantly decreased the delayed bleeding rate (0/19, 0%) compared with cases in which clips were not used (3/7, 42.9%; P = 0.013, χ2 test). Eighteen lesions (69.2%) were removed by en bloc resection. The follow-up period after resection was 25.5 ± 23.3 months. Two lesions (7.7%) that recurred locally were detected at the first surveillance endoscopy 3 months after resection. These lesions were 22 and 15 mm in size respectively and were resected piecemeal. Endoscopic resection is an effective and safe procedure for treating duodenal HGD/IMC. En bloc resection and prophylactic clip usage are encouraged.