Clinicopathological and Molecular Characteristics of Macroscopically Yellowish-Colored Chromophobe Renal Cell Carcinoma Compared to Non-Yellowish-Colored Chromophobe Renal Cell Carcinoma.

Each histological variant of renal cell tumors has a unique color. The yellowish color of clear cell renal cell carcinoma (CCRCC) is explained by the presence of intracytoplasmic lipid and glycogen accumulation. Color changes in CCRCC are correlated with clinicopathological and metabolic changes, as well as biological behavior. We analyzed and compared the clinical, histopathological, and immunohistochemical features and gene expression profiles, in lipid metabolism of yellowish-colored ChRCC (ChRCC-Y), non-yellowish-colored ChRCC (ChRCC-N), and CCRCC. Of 14 ChRCCs, we retrieved 6 ChRCC-Ys. Patients with ChRCC-Y are younger than those with ChRCC-N, and the tumor is not predominant in males. ChRCC-Ys are smaller than ChRRC-Ns. Three ChRCC-Ys exhibited individual discrete tubule formation. No ChRCC-Ns exhibited individual discrete tubule formation. Two of 6 ChRCC-Ys showed relatively diffuse adipophilin positivity. No ChRCC-Ns demonstrated diffuse positivity for adipophilin. The expression of SCD, FDFT1, and E2F1 showed a tendency to be lower in ChRCC-Y than in ChRCC-N. The expression of PDGFB showed a tendency to be higher in ChRCC-Y than in ChRCC-N. This study demonstrated ChRCC-Y did not indicate an increase in lipid and cholesterol metabolism and that ChRCC-Y did not have the common molecular alteration of CCRCC. The absence of such metabolic acceleration in ChRCC-Y might support the biological indolent behavior. Furthermore, we revealed that macroscopic color changes might be correlated with various clinicopathological features and immunohistochemical and molecular changes from different perspectives. We believe further characterization of RCC, including tumor heterogeneity, is needed to improve the management of patients with RCC.

Pathological complete response in a patient with metastatic pancreatic acinar cell carcinoma who received a chemotherapy regimen containing cisplatin and irinotecan.

Pancreatic acinar cell carcinoma is a rare tumor of the pancreas, and patients with such tumors rarely have a pathological complete response to treatment. Herein, we present a case involving a 48-year-old woman with a pancreatic tail mass. The pancreatic mass was connected to splenic and portal vein thrombosis. Distal pancreatectomy and removal of portal vein tumor thrombosis were performed. Ten months after surgery, multiple liver metastases and local recurrence in the pancreatic bed were detected, and chemotherapy was administered through the administration of a regimen containing both cisplatin and irinotecan. After seven courses of the cisplatin-plus-irinotecan regimen had been administered, computed tomography revealed that the patient had a partial response to treatment. Radical resection of multiple liver metastases and the locally recurrent tumor was performed. Pathological examination did not reveal the presence of carcinoma in any of the resected specimens. Thus, this case involves a pathological complete response in a patient with metastatic pancreatic acinar cell carcinoma who received a regimen containing both cisplatin and irinotecan. Our findings reveal that the administration of the cisplatin-plus-irinotecan regimen may be an option for the management of such tumors.

Estimated functional remnant pancreatic volume predicts nonalcoholic fatty liver disease after pancreaticoduodenectomy: use of computed tomography attenuation value of the pancreas.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a late complication of pancreaticoduodenectomy (PD). However, this complication is difficult to predict preoperatively. This study aimed to assess the association between NAFLD and preoperative computed tomography (CT) findings. METHODS: Medical records of 112 patients who had undergone PD and had CT scans preoperatively and 6 months postoperatively were retrospectively reviewed. We evaluated several CT findings, including the CT attenuation value of the remnant pancreas, remnant pancreatic volume (RPV), and the estimated functional remnant pancreatic volume (eFRPV) on preoperative CT. The variables, including the CT findings and histopathological findings, were compared between the patients with and without NAFLD after PD. RESULTS: The NAFLD group included 21 patients (18.8%). The CT attenuation value of the remnant pancreas was correlated with the pancreatic acinar cell density (r = 0.537), and was lower in the NAFLD group than in the non-NAFLD group (p = 0.007). The eFRPV was lower in the NAFLD group than in the non-NAFLD group (p = 0.002). An eFRPV ≤47 mL·HU was an independent predictive factor for NAFLD (p = 0.007; odds ratio: 6.73; 95% confidence interval: 1.70-26.70). CONCLUSION: The eFRPV can be used to preoperatively predict NAFLD after PD.

Two cases of benign hepatic nodules caused by sinusoidal dilatation with different hemodynamics.

We describe two cases of benign nodules caused by sinusoidal dilatation with different hemodynamic statuses. Case 1 was a 50-year-old woman with a 1-cm nodule that showed a low density in the arterial phase of computed tomography. Pathologically, there were no atypical cells with sinusoidal dilatation, and immunostaining was negative for CD34. We speculated that sinusoidal dilatation was caused by congestion due to loss of frequency of the central vein. In contrast, case 2 was a 50-year-old woman with a 1.5-cm nodule that was highly stained in the arterial phase of computed tomography. Although she had a sinusoidal dilatation similar to that in case 1, immunostaining was positive for CD34. Sinusoidal dilatation was thought to be caused by hyperperfusion of arterial blood. Moreover, CD34 may be potentially useful for the differentiation of the hemodynamic status.

Sclerosing Mesenteritis Mimicking IgG4-related Disease.

A 72-year-old man was followed as an outpatient at our hospital for 6 years after surgery for small cell carcinoma of left adrenal gland origin. Follow-up abdominal computed tomography showed a 6-cm mass in the left lower mesentery. The patient underwent open laparotomy. The histological diagnosis was sclerosing mesenteritis. The previous specimens of the left adrenal mass were then re-examined with a microscope, and panniculitis was found around the small cell carcinoma. Both lesions were histologically similar to IgG4-related disease (RD), but they did not completely meet the diagnostic criteria of IgG4-RD clinically or histologically.

Histological analysis of fundic gland polyps secondary to PPI therapy.

AIMS: The aim of this study was to clarify the histopathological features of fundic gland polyps (FGPs) in patients treated with proton pump inhibitors (PPIs) and to investigate the mechanism of enlargement of FGPs after PPI treatment. METHODS AND RESULTS: A total of 196 biopsy specimens of FGPs, which consisted of 87 FGPs in patients treated with PPIs (PPI group) and 109 FGPs in patients treated without PPIs (non-PPI group) were compared histologically using haematoxylin and eosin staining, Ki67 immunohistochemistry and multiplex immunohistochemical stain with Ki67, MUC5AC and MUC6. The significant histological features of FGPs in the PPI group were: larger size of dilated fundic gland cysts, larger number of foveolar and mixture type fundic gland cysts, foveolar cell hyperplasia, parietal cell protrusion, mononuclear cell infiltration and a higher percentage of Ki67-positive cells in the deeper layers of the glands. Multiplex immunohistochemical stain showed that Ki67-positive cells were also positive for MUC5AC, and the Ki67-positive rate was significantly higher in MUC5AC-positive cells of the PPI group than of the non-PPI group. Gene mutations of ß-catenin were found in only 9.7% of FGPs in the PPI group. CONCLUSIONS: Enlargement of fundic gland cysts due to foveolar cell proliferation and parietal cell protrusion might promote the enlargement of FGPs in patients treated with PPIs. ß-catenin gene mutations might not be associated with these histological changes of FGPs after PPI treatment.

Establishment and characterization of a mouse model of rhabdomyolysis by coadministration of statin and fibrate.

Rhabdomyolysis is characterized by elevation of plasma creatine phosphokinase (CPK) level, and multiple organ disorders, especially renal failure, as well as approximately 50% of acquired rhabdomyolysis are caused by pharmaceuticals. Statins are known to cause rhabdomyolysis, and its incidence is ≥10 times higher with coadministration of statin and fibrate. The purpose of this study is to establish a mouse model of drug-induced rhabdomyolysis by coadministration of statin and fibrate to clarify the mechanisms of its myotoxicity. We administered lovastatin (LV) and gemfibrozil (GF) with a glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO), to C57BL/6 J female mice once daily for 3 days. The plasma levels of CPK and aspartate aminotransferase (AST) were prominently increased, and the increase in plasma miR-206-3p and miR-133-3p levels, not the increase of miR-122-5p and miR-208-3p levels, suggested skeletal muscle-specific toxicity. The caspase 3/7 activity and mRNA levels of oxidative stress-related factors were elevated in skeletal muscle. Pharmacokinetic parameters showed that blood levels of statin were significantly increased by coadministered GF. The possibility of kidney injury was examined as in clinical rhabdomyolysis. In histological examination, vacuoles were observed in renal proximal tubules, and the plasma renal injury marker, lipocalin 2/neutrophil gelatinase-associated lipocalin (Lcn2/Ngal), was markedly increased in the mice coadministered LV and GF, suggesting mild complications of acute kidney injury. A quantitative comparison of the myotoxic potential of various statins was successfully performed using the present method. In this study, a rhabdomyolysis mouse model was established by coadministration of the clinically using statin and fibrate. This mouse model may be useful to identify drugs that have high risk for rhabdomyolysis.

Acute kidney injury model established by systemic glutathione depletion in mice.

Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug-induced rhabdomyolysis mouse model was recently established in L-buthionine-(S,R)-sulfoximine (BSO; a GSH synthesis inhibitor)-treated normal mice by co-administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only-treated mice. Therefore, in this study, we studied kidney injury in the GSH-depleted mouse. BSO was intraperitoneally administered twice a day for 7 days to normal mice. The maximum level of plasma creatine phosphokinase (351 487 ± 53 815 U/L) was shown on day 8, and that of aspartate aminotransferase was shown on day 6. Increased levels of blood urea nitrogen, plasma creatinine, urinary kidney injury molecule-1 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2/neutrophil gelatinase-associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347-203 925 ng/mL) and urine (2.5-68 583 ng/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb-stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH-depletion treatment established an acute kidney injury mouse model due to Mb release from the damaged skeletal muscle. This mouse model would be useful for predicting potential acute kidney injury risks in non-clinical drug development.