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Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. Up to 2011, approximately 300 cases had been reported worldwide. The average age of onset is 60.5 years old, with a prevalence of males (2:1). A typical finding of PMME is a lobular or polyploid, well-circumscribed and pigmented tumor, partly covered with normal mucosa. PMME represents various colors depending on its melanin quantity and commonly coexists with intramural metastases, melanocytosis or melanoma in situ. The tumor is located from the middle to lower thoracic esophagus. The accuracy of diagnosis from biopsy is approximately 80%, because many cases are misdiagnosed as a poorly differentiated carcinoma because of the absence of melanin granules. A definite diagnosis was made by immunohistochemical examination with positive results of S100 protein, HMB45 and neuron-specific enolase. PMME has a highly metastatic potential, and the incidence of distant metastasis at the initial diagnosis is around 40–80%. A metastatic tumor from cutaneous malignant melanoma is another pigmented esophageal tumor to be considered when making the differential diagnosis for PMME. Junctional activity with melanotic cells in the adjacent epithelium and the presence of in situ melanoma and/or a satellite tumor without a previous history of cutaneous melanoma are definitive. Most of the reported patients were treated with radical esophagectomy, which is believed to be an effective approach for localized PMME. Five-year survival rates have been achieved in 37% recently, while adjuvant therapy has not been proven to increase overall survival but plays a palliative role.

Aims: We aimed to clarify the endoscopic/clinicopathological features of superficial non-ampullary duodenal epithelial tumors (SNADETs) based on their mucin phenotypes. Methods: We analyzed 62 SNADET lesions and classified them based on mucin phenotypic expression. Endoscopic and clinicopathological findings were compared according to mucin phenotypes. Results: Eleven lesions had the gastric phenotype (GP) and 43 lesions had the intestinal phenotype (IP). All GP lesions were located in the first portion of the duodenum, while most IP lesions (72.1%) were located in the second portion (p < 0.01). Tumor size was significantly larger in the GP than in the IP group (14.4 mm vs. 10.2 mm, p < 0.05). Reddish color (72.7% in GP vs. 37.2% in IP, p < 0.05), type 0-I (72.7% vs. 11.6%, p < 0.01), lobular/granular pattern (81.8% vs. 4.7%, p < 0.01), and category 4/5 in Vienna classification (81.8% vs. 30.2%, p < 0.01) were observed significantly more often in the GP than in the IP group. Regarding findings of magnifying endoscopy with narrow-band imaging (M-NBI), white opaque substance (22.2% in GP vs. 89.7% in IP, p < 0.01) and light blue crest (0% vs. 43.6%, p < 0.05) were significantly less frequently observed in the GP group. Oval-shaped marginal epithelium (66.7% vs. 17.9%, p < 0.01), dense pattern (55.6% vs. 2.6%, p < 0.01), and dilatation of the intervening part (100% vs. 12.8%, p < 0.01) were more frequently observed in the GP group. Conclusions: SNADETs showed distinct endoscopic/clinicopathological features according to the mucin phenotype. Tumor location, coloration, macroscopic type, and endoscopic findings including M-NBI are useful to distinguish the mucin phenotypes of SNADETs.

Objectives The usefulness of 0.6% sodium alginate (SA) as a submucosal (SM) injection solution for endoscopic SM dissection (ESD) has gained attention over the past few years. However, using ESD for colorectal neoplastic lesions is not explicitly researched as yet. Thus, we conducted this study to determine the feasibility and safety of 0.6% SA solution for colorectal ESD. Methods In this single‐center, retrospective pilot study, a total of 100 cases treated with ESD using 0.6% SA as a SM injection solution for colorectal neoplasia at our institute were retrospectively reviewed to clarify the clinical feasibility and safety of 0.6% SA. The primary endpoint was to evaluate the complication rate, and the secondary endpoint was to determine the procedure time and the amount of solution used. Results Intraoperative perforation was observed in 1 case (1.0%), 2 cases (2.0%) presented with postprocedural hemorrhage, and no lethal adverse events were observed. The median ESD procedure times were 39.5 min (10–150), and the amount of solution used was less than 20 mL in 67 cases (67.0%). En‐bloc resection could be achieved in 97 cases (97.0%). Although six cases underwent subsequent surgery due to the deep SM invasion (>1000 μm), there were no cases with nodal involvement, confirmed through histopathological evaluation. Conclusions Our findings indicate that 0.6% SA can potentially ensure safe and secure ESD for colorectal neoplasia.

Background Acute kidney injury (AKI) is a common complication of cardiac surgeries. The incidence of AKI after cardiac surgeries using cardiopulmonary bypass (CPB-AKI) is high, emphasizing the need to determine strategies to prevent CPB-AKI. This study investigates the correlation between CPB-AKI and trace metal levels in clinical and animal studies.Methods Samples and clinical data were obtained from 74 patients from the Nagoya City University Hospital and Okazaki City Hospital. Blood samples were collected before, immediately after, and 2 h after CPB withdrawal. Trace metal levels were measured using inductively coupled plasma mass spectrometry. Sr or vehicle treatment was orally administered to the rats to determine if Sr was associated with CPB-AKI. After the treatment, ischemia–reperfusion (IR) injury was induced, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured.Results In this clinical study, the incidence of CPB-AKI was found to be 28% (21/74). The body mass index and estimated glomerular filtration rate were significantly different in patients with AKI. The intensive care unit and hospital stay were longer in AKI patients than in non-AKI patients. The Na, Fe, and Sr levels were significantly higher in AKI patients before CPB. Also, Fe and Sr were higher immediately after CPB withdrawal, and Sr was higher 2 h after CPB withdrawal in AKI patients. Animal studies showed that Sr-treated rats had significantly increased SCr and BUN levels than vehicle-treated rats at 24 h post-IR injury.ConclusionsHigh preoperative serum Sr levels may be associated with CPB-AKI.

Phosphodiesterase 5 inhibitors are widely used to treat erectile dysfunction and lower urinary tract symptoms with benign prostatic hyperplasia. Recent studies have indicated the renoprotective effects of this class of compounds. Whether renoprotection depends on blood pressure reduction remains controversial. In this study, we investigated the renoprotective effects of the phosphodiesterase 5 inhibitor, tadalafil, in a rat model of high‐salt induced kidney injury with hypertension. Dahl salt‐sensitive rats were fed a normal diet, high‐salt (8% sodium chloride) diet, or high‐salt diet with oral administration of either low‐ or high‐dose tadalafil (1 and 10 mg kg−1 day−1, respectively). Serum creatinine, urinary protein, and blood pressure were measured at baseline and after 8 weeks, at which point the rats were examined for glomerular injury and fibrosis. PAI1 mRNA levels were also evaluated. After 8 weeks, blood pressure, serum creatinine, and urinary protein levels were significantly higher in the high‐salt group than those in the normal‐salt group. Serum creatinine and urinary protein were significantly lower in both tadalafil groups than those in the high‐salt group, while only high‐dose tadalafil affected blood pressure. In addition, glomerulosclerosis and α‐smooth muscle actin expression significantly decreased in both tadalafil treatment groups. PAI1 mRNA increased significantly in the high‐salt group but decreased in both tadalafil‐treated groups. Our results indicated that both low‐ and high‐dose tadalafil prevented fibrosis and glomerular injury in a chronic kidney disease rat model. Mechanistically, these effects may be associated with PAI1 expression and glomerular structure protection. A PDE5 inhibitor, Tadalafil is renoprotective by preventing glomerular injury and fibrosis from high blood pressure. This study suggest that Inhibition of PDE5 might be effective to delay the CKD progression.

We report our experience of an extremely rare case of a simultaneous extrahepatic metastasis of hepatocellular carcinoma (HCC) with long-term relapse-free survival, treated by laparoscopic resection of an abdominal wall tumor and subsequent radiofrequency ablation (RFA) of an intrahepatic lesion. A 76-year-old man visited a local clinic for right lower abdominal pain. He was treated with antibiotics and the symptom resolved. However, a mass was detected in the same region and he was referred to our hospital for further evaluation. Computed tomography (CT) of the abdomen showed a mass 5 cm in diameter, raising suspicions of an intra-abdominal tumor. Laparoscopic surgery was performed, and the tumor was found in the abdominal wall and completely resected. Histopathological examination yielded a diagnosis of extrahepatic HCC. Post-operative positron emission tomography (PET)-CT showed increased uptake of fluorodeoxyglucose in segment 3 (S3) of the liver. On performing a liver biopsy, HCC was diagnosed. Subsequently, the S3 lesion was treated with radiofrequency ablation. The patient has remained relapse-free for 6 years without further treatments.

Thoracic duct injury leads to “chylothorax”. We found a close relationship of topographical anatomy between right bronchial artery and thoracic duct from esophageal cancer operations. We retrospectively analyzed topographical anatomy of right bronchial artery and location of thoracic duct in 124 cases operated in 2012. Of 124 cases, we recognized 8 cases of anomalous right bronchial artery. In these cases, the right bronchial artery originated directly from descending aorta without connections with third intercostal artery. When the right bronchial artery has a connection with third intercostal artery, the thoracic duct was located within the loop of the right bronchial artery. However, in these 8 anomalous cases, thoracic duct was located dorsally outside the loop of the right bronchial artery without exceptions. We have to be very careful in exploring the thoracic duct when we notice the anomalous right bronchial artery during esophageal cancer operation.

Background Esophageal squamous intraepithelial neoplasia (ESIN) as a precursor for invasive carcinoma is classified into low-grade IN (LIN) and high-grade IN (HIN), the latter including carcinoma in situ (CIS). Increasing grades of ESIN are associated with increasing risk of invasive carcinoma, but differentiation among LIN, HIN, and CIS is subjective and challenging. As p63, a member of the p53 family, is known to regulate differentiation and proliferation in epithelial progenitor cells, its expression, along with that of cytokeratin (CK) 14 (basal squamous marker) and Ki-67 (proliferation marker), might be of diagnostic assistance. Methods Immunohistochemical staining was performed on endoscopically resected specimens from 69 patients (73 lesions) with ESIN between 2008 and 2010. Specimens having no atypical cells distant from ESIN were defined as negative for IN (NIN). Results There were 13 LIN, 29 HIN, and 31 CIS lesions. The size of CIS (mean 20.1 mm) was significantly larger than that of HIN (14.3 mm) or LIN (10.0 mm). Immunolabeling scores (ILS) for p63, p53, CK14, and Ki-67 showed stepwise increase with ESIN progression (NIN vs. LIN and LIN vs. HIN, P  < 0.05–0.0001; HIN vs. CIS, P  < 0.05–0.001). Mean total ILSs of all four markers were 2.0 for NIN, 4.3 for LIN, 7.4 for HIN, and 9.1 for CIS ( P  < 0.0001). A cutoff value for total ILS of ≤5 versus ≥6 demonstrated highest sensitivity (96.0%) and specificity (85.7%) in distinguishing HIN from LIN. Conclusions This study suggests that p63 and p53 are coordinately upregulated in esophageal squamous carcinogenesis, and assessment of their expression might provide a useful adjunct tool for differential diagnosis of ESIN.

To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4) esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive preoperative treatment and underwent three-field lymph node dissection in the Juntendo University Hospital between December, 2004 and December, 2009. The tumors were histologically diagnossed as squamous cell carcinoma. The patients were divided into two groups, a surgery alone group (S group, 88 patients) and a group that received postoperative DCF therapy (DCF group, 51 patients). The disease-free and overall survival were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as N1 and N2, according to the TNM classification. There were no significant differences between the S and DCF groups regarding clinicopathological factors other than intramural metastasis and main tumor location. The presence of intramural metastasis, blood vessel invasion and the number of lymph nodes were identified as prognostic factors. The 5-year disease-free and overall survival were 55.8 and 57.3%, respectively, in the S group and 52.8 and 63.0%, respectively, in the DCF group. These differences were not considered to be statistically significant (P=0.789 and 0.479 for disease-free and overall survival, respectively). Although there were no significant differences in disease-free and overall survival between the S and DCF groups in N1 cases, both disease-free and overall survival were found to be better in the DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%, respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF was shown to improve disease-free and overall survival in moderate lymph node metastasis-positive cases (N2), suggesting that the DCF regimen may be effective as postoperative adjuvant chemotherapy for patients with lymph node metastasis from esophageal cancer.

Background The incidence of esophageal adenocarcinoma is only 1%–2% in Japan. For this reason, many aspects of this disease have not been clarified, such as its generation, progress, and the potential of malignancy. It is necessary to investigate the strategy for treating this disease. Methods Between 1998 and 2008, 19 cases were diagnosed as adenocarcinoma with Barrett’s esophagus and treated with esophagectomy at Juntendo University: 13 cases were early stage and 6 cases were advanced stage. Distribution of lymph node metastasis and prognosis were investigated. Results The incidence of lymph node metastases of adenocarcinoma is statistically lower (15.4%) compared with that of squamous cell carcinoma (SCC) (44.0%) ( P = 0.034) when the depth of the tumor is not beyond the submucosal layer. Even in the early stages of adenocarcinoma, positive nodes were found in the lower mediastinum and gastric cardia. In advanced cases, cancer had spread randomly to the upper mediastinum or celiac region. Mean survival time of superficial and advanced adenocarcinoma after esophagectomy was 3,517.5 ± 330.6 and 2,061.4 ± 451.3 days, respectively, whereas that of SCC was 2,794.7 ± 131.0 and 1,669.1 ± 101.5 days, respectively. Overall survival of superficial or advanced adenocarcinoma was better than that of SCC but was not statistically superior. Conclusions Endoscopic mucosal resection is limitedly proposed for mucosal tumors. Esophagectomy with a mediastinal lymphadenectomy should be conducted for tumors invading the submucosa. An individualized strategy is required that could approach the upper mediastinum based on staging and location of lymph node metastases.