Endoscopic ultrasound elastography for small solid pancreatic lesions with or without main pancreatic duct dilatation

Background/Objectives: Endoscopic ultrasound elastography (EUS-EG) is useful for diagnosis of small solid pancreatic lesions (SPLs), particularly in excluding pancreatic cancer (PC), but its dependence on main pancreatic duct dilatation (MPDD) has not been examined. We aimed to investigate EUS-EG for diagnosis of small SPLs with and without MPDD.MethodsPatients with pathologically diagnosed SPLs of ≤20 mm were included and retrospectively analyzed. Using the blue:green ratio, an EUS-EG image was classified as blue-dominant, equivalent, or green-dominant. Using multiple EUS-EG images per patient, a lesion with a greater number of blue-dominant than green-dominant images was classified as stiff, and the others as soft. EUS-EG images in random order were judged by three raters. Considering stiff SPLs as PC, diagnostic performance of EUS-EG was examined for SPLs with and without MPDD.ResultsOf 126 cases analyzed, 65 (52%) were diagnosed as PC, and 63 (50%) had MPDD. A total of 1077 EUS-EG images were examined (kappa coefficient = 0.783). Lesions were classified as stiff in 91 cases and soft in 35 (kappa coefficient = 0.932). The ratio of stiff to soft lesions was significantly higher in PC than in non-PC (62:3 vs. 29:32, P < 0.001). The sensitivity, specificity, and negative predictive value of a stiff lesion with vs. without MPDD for diagnosis of PC were 94%, 23%, and 50% vs. 100%, 60%, and 100%, respectively.ConclusionsUsing the EUS-EG stiffness classification for small SPLs, PC can be excluded with high confidence and concordance for a soft lesion without MPDD.     

Hepatic carcinosarcoma with heterogeneous carcinomatous and sarcomatous elements: report of a case and review of the literature

We report a rare case of hepatic carcinosarcoma consisting of two carcinomatous components and four sarcomatous components. A 54-year-old Japanese man presented with sudden right upper abdominal pain. Computed tomography showed a hepatic tumor measuring 17 cm in the greatest dimension and intractable ascites, suggesting rupture of hepatocellular carcinoma (HCC). Transcatheter arterial embolization was repeated at our hospital, resulting in stabilization of the patient’s general condition. Right anterior and left median sectionectomies were performed. Histologically, the tumor consisted of carcinomatous and sarcomatous elements. The carcinomatous elements consisted of moderately differentiated HCC (positive for hepatocyte antibody, murine monoclonal anti-cytokeratin antibody, and alpha-fetoprotein and negative for S-100 and desmin) and adenocarcinoma (negative for cytokeratin 7 and positive for carcinoembryonic antigen). Sarcomatous elements consisted of undifferentiated spindle cell sarcoma, rhabdomyosarcoma with acidophil striated cells including striped cells (desmin-positive), chondrosarcoma with cartilage matrix (S-100-positive), and osteosarcoma with osteoid. The sarcomatous elements were negative for epithelial markers. The patient is alive at 34 months after the operation with peritoneal dissemination. A total of 23 cases, including the present case, of hepatic carcinosarcoma have been reported in the English language literature. This is the third reported case of hepatic carcinosarcoma with heterogeneous carcinomatous and sarcomatous elements.     

Heterotopic pancreas in the stomach which caused obstructive stenosis in the duodenum

The patient, a 43-year-old Japanese man suffering from duodenal ulcer and reflux esophagitis, was admitted to our hospital because of submucosal tumor in the antrum and obstructive stenosis of duodenum. Several imaging tests could not rule out the possibility of malignant disease. Therefore, the patient was surgically treated. Pathohistological examination of resected tissue demonstrated Heinrich type I heterotopic pancreas in the gastric lesion and submucosal abscess in the duodenal lesion with stenosis. In this case, it was considered that the heterotopic pancreas caused chronic inflammation to form the gastric tumor, and submucosal abscess leading to the severe duodenal stenosis.     

Clinical analysis of HLA-DR-negative non-M3 AML

The type of leukemia was defined as HLA-DR(-) non-M3-AML, when HLA antigens were detected by flow cytometry at an incidence of < 20% of the blast population excluding M3-AML. Out of 109 patients with de novo acute myeloid leukemia, 8 patients had HLA-DR(-) non-AML-M3. According to the French-American-British criteria, 7 patients could be subdivided into 3 patients with M1, 4 patients with M2 and 1 patient with M4. The morphological features of bone marrow aspiration demonstrated no dysplasia and peroxidase stain positivity was noted in over 86% of the blast cells in all patients, the blast cells with fine granularity in 7 patients. The cytogenetic analysis revealed a normal karyotype. There was no expression marker of the blast antigens except CD13, CD14, CD33, CD34 and CD56. All of 7 patients who underwent induction therapy attained complete remission. Overall survival and disease-free survival showed no significant differences between the HLA-DR(-) non- M3-AML group and the HLA-DR(+) AML group.     

Identification and comparison of insulin pharmacokinetics injected with a new 4‐mm needle vs 6‐ and 8‐mm needles accounting for endogenous insulin and C‐peptide secretion kinetics in non‐diabetic adult males

Aims/Introduction

Many patients with diabetes now use 5‐, 6‐ or 8‐mm needles for insulin injection. However, it is unclear whether needle length, particularly for shorter needles, affects the pharmacokinetic properties of insulin.

Materials and Methods

This was a three‐way, randomized, cross‐over, single‐center study involving 12 healthy Japanese adult males (age 27.4 ± 4.14 years; weight 64.2 ± 5.2 kg; body fat percentage 18.2 ± 1.5%). Participants received a subcutaneous (abdomen) dose of insulin lispro (1.5 U for participants weighing 55 to <65.0 kg; 2.0 U for participants weighing 65.0 to <80.0 kg) delivered using a 32‐G × 4 mm (32G × 4), 31‐G × 8 mm (31G × 8) or 32‐G × 6 mm (32G × 6) needle with a 3–7‐day washout between doses. Pharmacokinetic parameters of exogenous insulin were identified using non‐linear least squares, where the total insulin concentration was fit to the measured plasma insulin concentration using an overall combined model that accounted for C‐peptide/insulin secretion in addition to the injected dose.

Results

Maximum concentration and area under the curve for 0 to infinity min for insulin were bioequivalent for the 32G × 4 needle relative to the 32G × 6 and the 31G × 8 needles. The time to the maximum insulin concentration was bioequivalent for the 32G × 4 needle relative to the 32G × 6 needle, but not the 31G × 8 needle.

Conclusions

The use of 4‐mm needles is unlikely to change the pharmacokinetic properties of insulin when injected subcutaneously in adults. This trial was registered with UMIN‐CTR (no. UMIN000004469).     

Effect of cilostazol, a phosphodiesterase inhibitor, on carotid IMT in Japanese type 2 diabetic patients

The aim of this study was to investigate the effect of cilostazol, a cAMP phosphodiesterase inhibitor, on carotid artery intima-media thickness (IMT) and on the incidence of cardiovascular events in Japanese subjects with type 2 diabetes. A total of 62 type 2 diabetic subjects were allocated equally to the cilostazol treatment group (n = 31) and the control group (n = 31). Carotid IMT was evaluated before and after treatment using B-mode ultrasonography. After the study period (mean +/- SD: 2.6 +/- 0.17 years), carotid IMT showed a significantly greater increase in the control group than in the cilostazol group (0.12 +/- 0.14 mm vs. 0.04 +/- 0.02 mm, p < 0.05). In the control group, 1 out of 31 patients suffered from symptomatic cerebral infarction and 1 had angina pectoris during the observation period. On the other hand, no subject in the cilostazol group developed cardiovascular events during the study period. At baseline, the diabetic patients given cilostazol had a significantly lower HbA1c level than the control subjects, but the other atherosclerotic risk factors (BMI, blood pressure, and serum lipids) and the duration of diabetes did not differ between the two groups. These results indicate that cilostazol therapy can attenuate the increase of carotid artery IMT in Japanese subjects with type 2 diabetes.     

Cytological findings of ROS1‐rearranged lung adenocarcinoma

ROS1‐rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1‐rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1‐rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet‐ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.