Surgical management of intraoperatively diagnosed portal annular pancreas: Two case reports.

RATIONALE: Portal annular pancreas (PAP) is a rare pancreatic anomaly characterized by portal vein encasement in the pancreatic parenchyma. Due to its rarity, PAP may often be missed on preoperative computed tomography (CT) review, and surgeons may face challenges in dealing with an unexpected intraoperative encounter with PAP. We documented 2 such intraoperatively diagnosed cases and illustrated their surgical management. PATIENTS CONCERNS: In case 1, a 70-year-old man was found to have a 15-mm mass in the pancreatic body and dilatation of the peripheral main pancreatic duct on enhanced CT. Case 2 involved a 46-year-old woman with a history of familial adenomatous polyposis, and rectal cancer with a mass in the duodenal papilla. DIAGNOSES: The patient in case 1 was diagnosed with resectable pancreatic cancer. In case 2, the patient was diagnosed with duodenal papillary carcinoma. INTERVENTIONS: In case 1, the patient underwent distal pancreatectomy with lymph node dissection. In case 2, the patient underwent pancreaticoduodenectomy. Intraoperatively, PAP was observed in both cases. In case 1, after the usual transection at the right border of the portal vein, an additional dissection was performed on the dorsal pancreas using a powered linear stapler. In case 2, an additional section was made in the pancreatic body caudal to the cricoid pancreatic junction so that the pancreatic cross-section was oriented in 1 plane. OUTCOMES: The patient in case 1 was discharged without complications. In case 2, although the patient had a grade-B pancreatic fistula (International Study Group of Pancreatic Fistula Classification), the patient recovered conservatively and was discharged without significant complications. In both cases, a retrospective review identified PAP in patients' preoperative CT images. LESSONS: Both cases required ingenuity during pancreatectomy. Awareness about PAP and its management will enable surgeons to prepare for unexpected encounters with the condition. Moreover, surgeons (especially pancreatic surgeons) should consider the possibility of PAP while managing pancreatic anomalies to make appropriate treatment decisions.

Sonodynamic Therapy Based on Combined Use of Low Dose Administration of Epirubicin-Incorporating Drug Delivery System and Focused Ultrasound.

Sonodynamic therapy (SDT) is currently considered as one of the promising minimally invasive treatment options for solid cancers. SDT is based on the combined use of a sonosensitizer drug and high-intensity focused ultrasound (HIFU) to produce cytotoxic reactive oxygen species (ROS) in and around neoplastic cells. Anthracycline drugs, including epirubicin (EPI), have been well known as effective sonosensitizers after interaction with focused ultrasound. Recently a new anticancer drug delivery system (DDS), NC-6300, has been developed that comprises EPI through an acid-labile hydrazone bond. In previous in vivo studies, NC-6300 showed basic drug safety and an excellent concentration property of EPI, and recently has been tested in clinical trials. For realizing minimally invasive cancer treatment, the present study demonstrated the effectiveness and feasibility of DDS-based SDT, which combined a small dose of NC-6300 and low energy of HIFU in mouse models of colon cancer and pancreatic cancer.

A fundamental study of cryoablation on normal bone: diagnostic imaging and histopathology.

Cryoablation is a minimally invasive cancer treatment. In this study, the effects of cryoablation on normal rabbit bone were evaluated using imaging and histopathological examinations. Cryoablation was performed using a Cryo-Hit (Galil Medical, Yokneam, Israel). Under anesthesia, one cryoablation needle was inserted at the center of the femur (day 0). To create an ice ball (2 x 3 cm), two 10-min freeze cycles were performed, separated by a 5-min thaw cycle. During cryoablation, changes in the bone and regional tissue were monitored using magnetic resonance imaging (MRI). MRI scans, computed tomography (CT) scans, and collections from the femur (for histopathological evaluation) were performed on days 7, 14, 28, and 56. In terms of the all rabbits' general conditions, we did not observe lameness, decreased appetite, or any other side effects during the experimental periods. Histopathological evaluations of the femur were performed using hematoxylin and eosin staining. MRI indicated inflammation around the ice ball on day 7. Subsequently, the area of inflammation gradually decreased from days 14 to 56. In the histopathological examination, necrosis of bone marrow cells and endosteum were observed from days 7 to 56. No regeneration of bone marrow cells was observed during the experimental period. On the other hand, cryoablation did not influence osteoblasts. Furthermore, there was no pathologic fracture during the experimental period. Our results suggest that cryoablation does not induce severe adverse effects on normal bone, and therefore has potential as a therapeutic option for bone tumors, including metastatic tumors to bone.

Ex vivo evaluation of high-intensity focused ultrasound with ultrasonic-induced cavitation bubbles.

PURPOSE: In high-intensity focused ultrasound (HIFU) comprising high-intensity burst ultrasound (triggering pulse) and medium-intensity continuous wave ultrasound (heating wave), optimizing the effects of the triggering pulse conditions on the coagulated volume may help to reduce treatment times. METHODS: HIFU combined with a triggering pulse was applied to chicken deep pectoral muscles. The acoustic power of the heating wave was set to 36, 54, or 72 W. Four different triggering pulse conditions were used: heating wave only; or pulse widths and pulse repetition frequencies of 30 µs and 1 kHz, 300 µs, and 100 Hz, or 3 ms and 10 Hz. RESULTS: Compared to the heating wave only condition, the coagulated volume was significantly larger under all conditions that included a triggering pulse. Significant differences were also observed in the ellipticity of the coagulated region between some conditions. CONCLUSION: HIFU combined with a triggering pulse may play an important role in reducing treatment times.

Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists.

To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl ω-chain moiety of the γ-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented.

Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists.

To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of γ-lactam prostaglandin E analogs bearing a 16-phenyl ω-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration.

Improved stability of OPALMON tablets under humid conditions. III: Application of the rotary vacuum drying method to dry Opalmon tablets.

In stability studies on moisture-resistant Opalmon tablets in press-through-packages (PTP), which were placed in aluminum bags, we found that the degradation rate of the dextran formulation is faster than that of the lactose formulation. The fast degradation of the dextran formulation is attributed to residual moisture in the package because drying the tablets before packaging suppressed the degradation and there is a good correlation between the stability of the drug and the water-activity of the tablets. Therefore, we developed a new drying method for the tablets, i.e. the rotary vacuum drying method, and investigated the effects of the operating conditions such as heating temperature, rotation speed, and vacuum degree on the drying time, and the appearance of the tablets. Using the rotary vacuum drying method, the tablets were dried over a short time (30 min) on a mass production scale so that the water activity was less than 0.03. Furthermore, the tablets suffered negligible damage such as breaking and chipping during the drying process. These results indicate that the rotary vacuum drying method is useful for drying tablets on mass production scales.